ACIP Meeting Day 1

26 June 2025

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Meeting Opening and Welcome

[Dr. Martin Kulldorff]

[0:14:03]
Good morning, I'm Dr. Martin Kulldorff, the chair of the Advisory Committee on Immunization Practices. Today is June 25, 2025, and I'm pleased to call today's ACIP meeting to order. I wish you all welcome and I thank you for being here. I want to thank both the voting and ex-officio members and liaisons of the committee who will shortly introduce themselves. I would also like to take this opportunity to thank the former committee members. Serving on this committee is a time-intensive and not always appreciated task. I also want to thank the devoted CDC researchers and staff who have done a great job of investigating these matters, assembling the experts, and putting together the agenda and presentation content.

Importance of ACIP Recommendations

[0:15:07]
ACIP recommendations have an impact on the health and lives of Americans from infancy to old age. Nothing is more precious to those of us on this panel than our children and grandchildren. And likewise, we know they are nothing more important to parents than the health of their children. Our recommendations cover the lives of over 70 million mostly healthy children. Secretary Kennedy has given this committee a clear mandate to use evidence-based medicine when making vaccine recommendations, and that is what we will do.

Mandate for Evidence-Based Medicine

Nuance of Vaccine Evaluation

Vaccines are not all good or bad. If you think that all vaccines are safe and effective and want them all or if you think that all vaccines are dangerous and don't want any of them, then you don't have much use for us.

[0:16:05]
You already know what you want. But if you wish to know which vaccines are suitable for you and your children and at what ages, then we will provide you with evidence-based recommendations.

Welcome to Public Participants

I'm very glad that there's so much interest in the work of this committee, and I want to especially welcome members of the public with us today remotely. It is wonderful that you take an interest in vaccines, medicine, and science.

Encouraging Questions and Scientific Method

If you have questions or concerns about the safety or efficacy of vaccines, we want to hear them. That is the scientific method, and it is natural to ask questions. That is what the CDC subject matter experts do. It's what the public does, and it is what we will do. No questions should be off limits.

[0:17:02]
Some media outlets have been very harsh on the new members of this committee, issuing false accusations and making concerted efforts to put scientists in either a pro- or anti-vaccine box.

Addressing Media Criticism

Such labels undermine critical scientific inquiry, and it further feeds the flames of vaccine hesitancy.

Analogy of Mercury in Fish and Vaccines

As Secretary Kennedy has eloquently stated, opposing mercury in fish does not make you anti-fish, and opposing mercury in vaccines does not make you anti-vaccine. In fact, to thoroughly scrutinize and ensure the safety and efficacy of vaccines is a pro-vaccine position.

Scrutinizing Safety as a Pro-Vaccine Stance

Analogy of Aviation Safety

Just like the promotion of aviation safety is a pro-airline position. Millions of Americans board an airplane each day. While airlines fiercely compete when it comes to schedules, ticket pricing, and service, there is one thing they collaborate very closely on, and that is safety.

[0:18:08]
If one airline ignores safety concerns or has a plane crash, that affects the public trust in and willingness to travel with all other airlines.

Impact of Adverse Reactions on Public Trust

The same is true for vaccines. When there are unexpected adverse reactions or when concerns are cut concerning the safety of one vaccine, that affects all other vaccines, reducing vaccine uptake and coverage. Rebuilding public trust through sound science is very important.

Rebuilding Public Trust

For example, the inflated promises about the COVID vaccines preventing transmission and disease and COVID vaccine mandates have decreased overall public trust in vaccines.

[0:19:00]
Messages stemming from evidence-based science on the safety and efficacy of vaccines is in the best interest of the public, industry, and public health institutions.

Message to Fellow Scientists

Lastly, I wish to address my fellow scientists in the audience. It is no secret to anyone in this room that confidence in public health institutions, including CDC, FDH, FDA, NIH, and university leadership fell during the pandemic and that it is at an all-time low. Most scientists are honestly seeking the truth in their research, and that includes scientists here at CDC. We must work to rebuild integrity and trust, and we do that by honestly recognizing past mistakes, adhering to evidence-based medicine, and encouraging open scientific discourse as uncomfortable as that may be.

Rebuilding Integrity and Trust

I hope you will join me in this quest.

[0:20:03]
I will now turn it over to the ACIP Executive Secretary. Please, Mina.

Introduction of ACIP Executive Secretary

[Dr. Mina Zadeh]
Thank you, Dr. Koldolf. Good morning, everyone. I'm Dr. Mina Zadeh, and I'm serving as the designated federal officer for the Advisory Committee on Immunization Practices. Welcome to the June 25th to 26th, 2025 ACIP meeting.

Procedural Items

Before introducing our new ACIP members and conducting roll call, I'd like to review a few procedural items. Presentation slides are or will soon be available on the ACIP website. For those participating remotely, please remain muted unless called upon. Use the raise hand feature to request recognition during discussion. Questions will be taken from voting members and ex-officios followed by liaison representatives as time permits.

[0:21:00]
Please keep your video off. Profile images are acceptable. Next slide, please. The Advisory Committee on Immunization Practices is a public advisory body, and engagement with the public and transparency in our processes are central to the committee's work.

Public Advisory Body and Transparency

For this meeting, we will be holding two oral public comment periods.

Oral Public Comment Periods

The first will be held today at 4.15 p.m. Eastern time. The second will be held tomorrow, June 26th, at approximately 11.30 a.m. Eastern time. To create a fairer and more efficient process for requesting to make an oral comment, we ask those interested to submit a request online in advance of the meeting.

Process for Requesting Oral Comment

We give priority to advanced requests, and if there are more requests than can be accommodated in the allotted time, we select speakers through a blinded lottery. The 30 speakers selected by lottery for this meeting have already been notified.

Notification of Selected Speakers

[0:22:04]
We thank all those who requested an opportunity to make a public comment.

Written Public Comments

Members of the public also had the opportunity to submit written public comments on issues via regulations.gov. The docket number for today's meeting is CDC 2025-0024. More information on the public comment process can be found on the ACIP meeting website. Next slide, please.

Conflict of Interest Policies

As outlined on the ACIP policies and procedures manual, members agree to refrain from certain vaccine-related activities while serving on the committee. CDC may grant limited conflict of interest waivers for activities that support a member's expertise. Members who conduct vaccine clinical trials or serve on data safety monitoring boards may present on those topics but are prohibited from voting on related issues. If a member has an association with a company's vaccine, they may participate in discussion but must abstain from all votes concerning that company's vaccines.

Declaration of Conflicts

[0:23:09]
At the start of each meeting, members are asked to declare any relevant conflicts of interest.

Introduction of New ACIP Members

Next, I'd like to welcome our new ACIP members. Please introduce yourselves briefly and describe your background and disclose any conflicts relevant to this meeting. And if you don't have any conflicts, please state that you don't have any conflicts. I'll start with our chair, Dr. Martin Kulldorff.

Introduction of Dr. Martin Kulldorff

[Dr. Martin Kulldorff]
Thank you so much, Dr. Sadev. So, I'm Martin Kulldorff. I have worked on vaccine safety for over 20 years. I am very closely involved with the CDC's Vaccine City Data Link and the FDA Sentinel Initiative, helping developing their vaccine safety surveillance and monitoring program.

[0:24:03]
I used to be a professor of medicine at Harvard University and at Harvard Spring and Women's Hospitals until I was fired. I did not take the COVID vaccine because I already had immunity, superior immunity, from having had COVID. And I was astonished that universities threw away 2,500 years of knowledge about infection acquired immunity when they very unscientifically and unethically fired people for not having taken the COVID vaccine. I used to serve on two workgroups under ACIP in the past. One was for the COVID-19 vaccine safety, but I was removed from that committee because I objected to the pass of the J&J vaccines. There were reports of blood clots in young women.

[0:25:03]
So, it made sense not to give them the vaccine, but I objected to the pass of older Americans because there was a shortage of vaccines and people were dying. So, I think that pass of the J&J vaccine was inappropriate. And actually, I think some Americans died because of it. So, in that case, I was, I guess, the most pro-vaccine person among vaccine scientists in this country. So, it's kind of a little bit ridiculous that the media says that I'm anti-vaccine. So, but that is as it is. So, please, next person. Oh, yeah. During my work with vaccines, I've never accepted any money from pharmaceutical companies manufacturing vaccines. I don't have any conflict of interest with any of the topics of today's meeting.
[Dr. Mina Zadeh]
Thank you.

Introduction of Dr. Joseph Hiblin

[0:26:00]
We'll do it in alphabetical order. Dr. Hiblin.
[Dr. Joseph Hiblin]
I'm Joseph Hiblin, and I was a commissioned officer in the United States Public Health Service for 30 years and have dedicated myself both as a physician and an intramural scientist to the best quality of science. And I am absolutely honored to participate in this tremendous public health endeavor of protecting our infants, our mothers, ourselves, and the world from deadly viruses that we don't always understand. I am honored by the intellect and the capacity of my fellow committee members. I am currently a distinguished visiting professor at the University of Bristol, and I have approached this committee and these issues with a neutral scientific mind, completely evaluating the data presented to us to make the best decisions for public health, and I have no conflicts of interest.

[0:27:10]
Thank you.

Introduction of Dr. Rezif Levy

[Dr. Mina Zadeh]
Thank you. Dr. Levy.
[Dr. Rezif Levy]
Hi. Good morning, everybody. I'm Rezif Levy. I'm serving on the faculty of MIT since 2006. I have a PhD in operations research from Cornell University, and my research is focused on the use of data, advanced analytics, and modeling to inform and optimize risk-benefit decisions and system design and operations. And much of my research over the have been focused on human health. Specifically, I have over 19 years of working in healthcare systems very closely with clinicians.

[0:28:04]
I have done work on safety and quality in manufacturing of biologics, developed epidemiological models, post-marketing drug and safety surveillance models. I also have work on issues related to water and food and agriculture systems that also have a major impact on human health, and I also have been involved in work on the COVID-19 vaccines. I'm delighted, honored, and humbled to be here today, and I look forward to working with my colleagues on the committee and with the CDC staff members and others on the very, very important issues that are in front of us, and hopefully together learn what the data and the evidence and the science are telling us about the best recommendations for the public in the U.S. and beyond, and looking forward for hard work.

[0:29:06]
And I don't have any conflict of interest with respect to the issues that will be discussed in the coming meeting.
[Dr. Mina Zadeh]
Thank you.

Introduction of Dr. Robert Malone

Dr. Malone?
[Dr. Robert Malone]
My name is Robert Malone. I'm a Maryland licensed physician and scientist. I have been secret cleared by the U.S. Department of Defense, extensively vetted. I've now been through three months of vetting and training regarding COI with HHS. I have no conflicts of interest. Those potential, any potential conflicts of interest, have been analyzed and vetted and declared lacking, both internally by HHS and specifically by CDC.

[0:30:00]
My relevant background is that I've been working in virology, immunology, molecular biology, pathology since 1983, beginning in a laboratory focused on retroviruses and intimately involved in initial findings relating to what we now call HIV. I've had done, I've worked in academia to associate professor most recently at the Uniform Services University of Health Sciences in D.C. I've worked for the government at length, particularly with Defense Threat Reduction Agency and in the biodefense space, including the prime systems contractor, Dynport Vaccine Company, that had responsibility for virtually all DOD-related vaccines and threat mitigations for biowarfare agents.

[0:31:03]
I've worked for ARIS Global TB Vaccine Foundation and Tuberculosis Vaccine Development, which is a Bill and Melinda, was a Bill and Melinda Gates funded non-governmental organization. I've worked in industry in regulatory affairs. I'm an expert in clinical research, regulatory affairs, project management, and contracting with extensive government experience, particularly with Defense Threat Reduction Agency. Regarding specifically vaccines, my experiences included influenza, seasonal and pandemic vaccine development, including a senior management position at Salve Vaccines, managing a $300-plus million contract for cell-based influenza.

[0:32:07]
I've been an invited speaker at the World Health Organization to a lecture on novel influenza vaccine manufacturing technology. I have experience in HIV, anthrax, plague, tuberculosis, and virtually all of the classical biodefense-related vaccine products that are currently in the pipeline. My core competence, again, is in virology, immunology, pathology. I taught pathology for many years in academe, molecular biology, and in particular, polynucleotide delivery. Thank you.
[Dr. Mina Zadeh]
Thank you.

Introduction of Dr. James Pagano

We'll go to Dr. Pagano, and then afterwards, we'll go to our online members.
[Dr. Robert Malone]
Good morning.

[0:33:01]
I'm James Pagano, a retired emergency physician with over 40 years of experience in patient care and department management.
[Dr. Cody Meissner]
I chose that specialty, which was brand new at the time, because it offered me the chance to provide expert care to the entire spectrum of the patient population, from infants to the elderly, regardless of their background, regardless of their ability to pay, when they needed that care most in an emergency and often under difficult circumstances.
[Dr. Robert Malone]
This is the perspective and mindset I bring to this committee. I'm honored to be here. I have no conflicts.

Introduction of Dr. Cody Meissner (Initial Technical Difficulties)

[Dr. Mina Zadeh]
Thank you. Dr. Meissner, I think we have to unmute for him to be able to speak.

[0:34:04]
I think we have to unmute.
[Dr. Cody Meissner]
Yes.
[Dr. Mina Zadeh]
To be able to speak.
[Dr. Cody Meissner]
Yes. Thank you, Mina. And I hope that everyone can hear me.
[Dr. Mina Zadeh]
Yes, we can hear you.
[Dr. Cody Meissner]
Thank you. I welcome everybody, those online and who are listening to this meeting.
[Speaker 31]
I think we have to unmute.
[Dr. Cody Meissner]
Yes.
[Dr. Mina Zadeh]
To be able to speak.
[Dr. Cody Meissner]
Yes. Thank you, Mina. And I hope that everyone can hear me.
[Speaker 31]
Yes, we can hear you.
[Dr. Cody Meissner]
Thank you. I welcome everybody, those online and who are listening to this meeting. Yes. To be able to speak. Okay. Yes. Thank you, Mina. I'm not sure what's happening. There's an echo here.
[Speaker 31]
Yes, we can hear you.
[Dr. Cody Meissner]

[0:35:00]
Thank you. We're looking into it. I welcome everybody, those online and who are listening to this meeting. I think there's a problem. Yes. Okay. Yes. Thank you, Mina. I'm not sure what's happening. We can hear you. There's an echo here.
[Dr. Mina Zadeh]
Yes. Thank you. We're looking into it. I welcome everybody.
[Dr. Cody Meissner]
Okay. Why don't you come back to me when it gets straightened out.
[Dr. Mina Zadeh]
Maybe if we can go to our next member, Dr. Pepsworth.

Introduction of Dr. Vicki Pepsworth (Technical Difficulties)

She also needs to be unmuted, please.

[0:36:11]
Dr. Pepsworth, I think you can unmute. Maybe we'll be able to hear you. Dr. Pepsworth, can you hear us? If you can unmute.
[Dr. Vicki Pepsworth]

[0:37:55]
Hi, can you hear me now?

Dr. Vicki Pepsworth Introduction (Audio Restored)

Yes, we can hear you. Thank you. Sorry about that.

[0:38:01]
My name is Vicki Pepsworth, and I've worked in the healthcare field now for about 45 years. I have doctoral degrees in nursing and in public health from the University of Michigan. My public health background is in health services organization and policy. I previously served on the FDA's VRBPAC committee for quite a few years. I also served on two committees at the National Vaccine Advisory Committee. I currently am a volunteer as the director of research at the non-profit National Vaccine Information Center. I'm also the Pacific region director of the National Association of Catholic Nurses. As it relates to conflicts of interest, I have been asked to read the following statement. As required under the ACIP policies and procedures, I am also disclosing that I own stock in a healthcare sector fund that includes holdings relevant to the ACIP, including vaccine manufacturers.

[0:39:13]
However, the amount of that stock holding is under the Office of Government Ethics Regulatory De Minimis amount. I understand that I, therefore, can fully participate in the ACIP meeting. Thank you very much. I look forward to being of service and working hard to improve policymaking decisions for vaccines. Thank you.

Dr. Cody Meissner Introduction (Audio Restored)

[Dr. Mina Zadeh]
Thank you, Dr. Meissner.
[Dr. Cody Meissner]
I apologize for the technical difficulty on my end. I am, my name is Cody Meissner. I am currently a contractor supporting the Biomedical Advanced Research and Development Authority, that is BARDA, and I'm also a professor at Geisel School of Medicine at Dartmouth.

[0:40:13]
I've had a longstanding interest in vaccines and public health. I have previously served on ACIP, on VRBPAC. I was chair of the National Vaccine Injury Compensation Program, and I have worked in the past extensively with the American Academy of Pediatrics. I am delighted to be able to present my perspective to the committee. Thank you.
[Dr. Mina Zadeh]
Thank you.

Introduction of Ex-Officio Members

And now I'll go through our ex-officio members. If you would please let us know who's present from your agency, and I'll try to go through this as fast as possible.

[0:41:07]
Centers for Medicare and Medicaid Services.

Centers for Medicare and Medicaid Services

[Dr. Cody Meissner]
Good morning. Andrew Johnson, Senior Advisor, Centers for Medicare and Medicaid Services.
[Dr. Mina Zadeh]
Thank you.

Food and Drug Administration

Food and Drug Administration.
[Dr. Tracy Beth Hoag]
Present, Tracy Beth Hoag, Physician Scientist. I'm Senior Advisor for Clinical Sciences in the Office of the Commissioner and the Center for Biologics Evaluation and Research. Thanks. Thank you.
[Dr. Mina Zadeh]
Health Resources and Services Administration.

Health Resources and Services Administration

Anyone online?
[Speaker 31]
Does she want, is she introducing?
[Dr. Mina Zadeh]

[0:42:00]
Okay. Indian Health Services.

Indian Health Services

I have Matt. Matt Clark.

National Institute of Health

And the National Institute of Health.

Introduction of Liaison Representatives

Now I'm going to go through our liaison representatives. American Academy of Family Physicians.

American Academy of Family Physicians

Sorry, I think we're having technical difficulty.

[0:43:11]
We're going to go to the next section, which is the workgroup updates, and then come back to roll call since we're having difficulty.

Postponement of Roll Call for Workgroup Updates

Thank you. I'll turn it over to Dr. Kulldorff.
[Dr. Martin Kulldorff]
So hopefully we can have them introduced a little bit later on.

Role of Workgroups

Workgroups play a very important role in the work of the ACIP. Selected from around the country, workgroup members are experts on the vaccines, diseases, and safety issues under consideration. They investigate issues in detail and forward recommendations to the ACIP.

Workgroup Structure and Continuity

Workgroups must be shared by an ACIP member.

[0:44:01]
So new shares are currently being appointed to the existing workgroups. Other workgroup members have been retained. It's important that we build on the progress that has already been made, and we are very grateful for the work that has been done to date by these workgroups.

Existing Workgroups

There are currently 11 important workgroups looking at vaccines for chikungunya, COVID-19, cytomegalovirus, human papillomavirus, influenza, meningococcal disease, mpox, pneumococcal disease, and RSV, respiratory syncytial virus.

Future Workgroup Reports

We are looking forward to receiving reports from these workgroups at future ACIP meetings. When there are different views among working groups members, we want to hear both the majority and minority views.

Hearing Majority and Minority Views

Establishment of New Workgroups

[0:45:02]
Some new workgroups will also be established. The number of vaccines that our children and adolescents receive today exceed what children in most other developed nations receive, and what most of us in this room received when we were children.

Evaluating the Cumulative Vaccine Schedule

In addition to studying and evaluating individual vaccines, it is important to evaluate the cumulative effect of the recommended vaccine schedule. This includes interaction effects between different vaccines, the total number of vaccines, cumulative amounts of vaccine ingredients, and the relative timing of different vaccines. The Institute of Medicine, which is now the National Academy of Medicine, wrote an important report on these issues some years ago, arguing for more research on this topic.

Institute of Medicine Report

And it is now time to evaluate that new research. Towards that end, we will be establishing a workgroup that will look at the cumulative childhood vaccine schedule, as well as the adolescent schedule.

Workgroup on Cumulative Schedule

[0:46:09]
We will also be convening a new workgroup to look at vaccines that have not been subject to review in more than seven years.

Workgroup on Vaccines Not Reviewed in Seven Years

This was supposed to be a regular practice of the ACIP, but it has not been done in a thorough and systematic way. We will change that. We are learning more about vaccines over time, and to stay true to evidence-based medicine, we have a duty and responsibility to keep up to date with scientific research to make sure that ACIP recommendations are optimal for both individuals and public health.

Duty to Stay Up-to-Date with Research

Hepatitis B Vaccine at Birth

Among other topics, this new vaccine group may look at the universally recommended hepatitis B vaccine at the day of birth. Is it wise to administer a birth dose of hepatitis B vaccine to every newborn before leaving the hospital? That's the question.

[0:47:01]
Unless the mother is hepatitis B positive, an argument could be made to delay the vaccine for this infection, which is primarily spread by sexual activity and intravenous drug use.

Measles Vaccine Timing and Options

Vaccines are important for combating measles. For the first dose at age 12 to 15 months, a previous ACIP meeting recommended two alternative options equally, with either separate MMR and varicella vaccines in two different needles, or the combined MMRV vaccine in one needle, even though the latter cause an excess number of febrile seizures. Aware of this, most pediatricians administer separate MMR and varicella vaccines, and CDC has also expressed a preference for that. To minimize vaccine adverse reactions, the ACIP may follow the lead of pediatricians and reevaluate its earlier recommendation concerning MMRV for one-year-old children.

[0:48:01]
This working group may also look at new research concerning the optimal timing of the MMR vaccine to resolve religious objections that some parents have concerning the MMR vaccine being used here in the United States. They could also look at other MMR vaccines, such as the one used in Japan.

Collaboration with Workgroups and CDC Scientists

While we may bring different perspectives on some issues, we look very much forward to working collaboratively with the current members of the existing workgroups, as well as with scientists here at CDC. We share the same goal, the improvement of public health. That can only be achieved through close collaboration, open discussions, and most importantly, with evidence-based medicine. Thank you.
[Dr. Mina Zadeh]
Thank you for that update.

COVID-19 Vaccines Session Introduction

Now we can start our presentations. Our first topic is COVID-19 vaccines.

[0:49:04]
I'm going to turn it over to Dr. McNeil.
[Ben Spader]
Morning. Is this projecting? Okay, great. Good morning.

COVID-19 Session Agenda

My name is Adam McNeil. I serve as Acting Director for the CDC's Coronavirus and Other Respiratory Viruses Division. The COVID session today will include information on the epidemiology of COVID-19, as well as COVID-19 vaccine effectiveness, safety, and implementation. These presentations include data from two evidence to recommendation domains that the COVID-19 workgroup has reviewed, which are the public health problem and benefits and harms. I want to upfront acknowledge and thank all the CDC employees and collaborators who contributed to the data and content of these presentations.

[0:50:08]
Outlined on this slide is the agenda for the session. After a brief introduction, I will present on COVID-19 epidemiology and updates on COVID-19 vaccine effectiveness. Dr. Sarah Meyer will then give an update on vaccine safety. Dr. Georgina Peacock will present on COVID-19 vaccine coverage and implementation, and I'll wrap up the session by presenting a summary of the first two domains of the evidence to recommendations. Please note that PDF versions of these slides have all been posted on the ACIP website, which is available to the public. To recap the events of the past year, last June, ACIP recommended 24-25 COVID-19 vaccination for all people age six months and older.

Recap of Past Year's Recommendations

In August, FDA authorized Moderna, Pfizer, and Novavax COVID-19 vaccines.

[0:51:01]
And in September, ACIP's recommendations and CDC vaccination guidance was published in MMWR. At the October 2024 ACIP meeting, the committee recommended additional doses for adults age 65 and older and people six months and older with moderate or severe immunocompromised, which was then published in MMWR in December 2024. As has been customary after every recommendation change, CDC updated the interim clinical considerations with these changes following vaccine availability in August, September, and October of 2024. Last month, in May 2024, per HHS directive, CDC updated the COVID-19 vaccine recommendations to shared clinical decision-making for healthy children age six months to 17 years and no guidance not applicable for pregnant women.

Recent Recommendation Updates

Also, last month, FDA approved Novavax's COVID-19 vaccine and Moderna's mSpike for people ages 12 to 64 years at high risk for severe COVID-19 and for people ages 65 and older.

FDA VRBPAC Meeting and Strain Selection

[0:52:10]
On May 22, 2025, FDA's VRBPAC met to discuss strain selection for the 25-26 COVID-19 vaccines. FDA then advised manufacturers that the 25-26 formula should be monovalent JN1 lineage-based antigen composition, preferentially using the LP8.1 strain. Here is an overview of the current routine COVID-19 vaccine schedule by age group.

Current Routine COVID-19 Vaccine Schedule

Children age six months to four years who are unvaccinated may receive a multi-dose initial series with a 24-25 COVID-19 mRNA vaccine using shared clinical decision-making. Those who have previously completed an initial series may receive one dose of a 24-25 mRNA vaccine from the same manufacturer's initial series using shared clinical decision-making.

[0:53:04]
People age five to 17 years may receive one age-appropriate dose of the 24-25 COVID-19 vaccine using shared clinical decision-making. Adults aged 18 to 64 years should receive one dose of any 24-25 COVID-19 vaccine, and those age 65 and older should receive two doses of any 24-25 COVID-19 vaccine spaced six months apart.

Recommendations for Immunocompromised Individuals

The current recommendations for people with moderate or severe immunocompromised are shown on this slide. People who are moderately or severely immunocompromised and unvaccinated should receive a multi-dose vaccination series with an age-appropriate 24-25 vaccine and receive one 24-25 vaccine dose six months after completing the initial series. Those who have previously completed an initial series should receive two doses of an age-appropriate 24-25 COVID-19 vaccine spaced six months apart, and they may receive additional age-appropriate 24-25 COVID-19 vaccine doses under shared clinical decision-making.

Interim Recommendations and Evolution

[0:54:16]
Very important to note, COVID-19 vaccines have had interim recommendations since 2020. These ACIP recommendations were made based on the best available information at the time with the understanding that these recommendations would be regularly revisited and potentially evolve over time.

Consideration of Non-Universal Recommendations

For the past several years, the workgroup has been considering non-universal recommendations for COVID-19 vaccination, meaning that only certain age or risk groups would be recommended. At the ACIP meetings in September 2023 and June 2024, the workgroup interpretations summary outlined discussions that the workgroup had around universal and non-universal policy options for the 2023-24 and the 2024-25 vaccines, respectively.

[0:55:05]
Ultimately, based on the totality of the evidence, including the epidemiology of COVID-19 and implementation considerations, the workgroup felt that a universal recommendation was the best option.

Workgroup Discussions and Proposed Recommendations

Beginning in November 2024, the workgroup has discussed 25-26 COVID-19 vaccine recommendations, and at the April 25 ACIP meeting, ACIP members discussed considerations for the 2025-2026 recommendations, potentially moving to a non-universal recommendation. Between November 2024 and June 2025, the COVID-19 workgroup reviewed epidemiology and burden of COVID-19 disease, vaccine effectiveness, vaccine safety, and implementation. At the most recent workgroup meeting on June 5th, and in polling after the meeting, the workgroup agreed to the following groups and recommendation types.

[0:56:00]
Age appropriate 2025-2026 COVID-19 vaccines for all infants and children aged 6 to 23 months. Age appropriate 2025-2026 COVID-19 vaccine for persons aged 2 to 64 years for the following groups. Persons at high risk for severe COVID-19, including pregnant women. Persons at high risk of exposure. Shared clinical decision making for persons desiring additional protection from COVID-19. And two doses of 2025-2026 COVID-19 vaccines for adults aged 65 years, and people 6 months and people less than or greater than 6 months with moderate or severe immunocompromise. Next, we will move to COVID-19 epidemiology.

COVID-19 Epidemiology Presentation

[0:57:06]
This presentation starts with some overall epidemiology related to COVID-19 associated hospitalizations, and then we'll focus first on children, including infants, followed by adults and pregnant women. Finally, I'll give an update on current genomics of SARS-CoV-2. COVID-19 continues to impact Americans' health.

Impact of COVID-19 on American Health

Using COVID-NET data and other sources, CDC estimates that since October 1st, 2024, there have been between 9.8 and 16.1 million COVID-19 associated illnesses, between 2.4 and 3.8 million COVID-19 associated outpatient visits, between 270,000 and 440,000 COVID-19 associated hospitalizations, and between 32,000 and 51,000 COVID-19 associated deaths.

Long COVID

[0:58:02]
Long COVID, also known as post-COVID condition, is a significant public health threat that occurs following COVID-19. National surveys in 2023 estimated approximately 9.2 million adults and 3.3 million children in the U.S. had long COVID. Among adults, 3.6 percent reported long COVID symptoms and 8.4 percent reported ever having long COVID. Among children, 0.4 percent reported long COVID symptoms and 1.4 reported ever having long COVID. More than three in five adults and almost four in five children with long COVID reported activity limitations.

COVID-19 Associated Hospitalization Surveillance Network (COVID-NET)

Much of the epidemiologic data presented today will be data from the COVID-19 Associated Hospitalization Surveillance Network, or COVID-NET. COVID-NET is one of three REST-NET platforms, in addition to RSV-NET and FluServe-NET, that collect data using similar methods and catchment area on laboratory-confirmed COVID-19, RSV, and influenza-associated hospitalizations, respectively.

[0:59:15]
COVID-NET is a population-based surveillance system that collects and reports data from more than 300 acute care hospitals in 185 counties across 13 states. The COVID-NET catchment area includes about 10 percent of the U.S. population. Hospitalizations reported to COVID-NET include all those where a positive COVID-19 test result was reported within 14 days prior to hospitalization. Testing for SARS-CoV-2 is driven by clinical judgment and facility policies. Basic demographic data are collected on all patients, while detailed clinical data are collected by trained surveillance officers from an age and site-stratified random sample.

COVID-NET Data Period

For this presentation, the period of population-based rates of COVID-19-associated hospitalizations is July through June.

[1:00:07]
This period allows us to present data for periods that are inclusive of both the typical respiratory virus season of October through April, as well as the increase in rates which we have experienced over the preceding summer for COVID-19. Clinical data are presented for the most recent 12-month period of April 2024 through March 2025. The next two slides will show weekly hospitalization rates for COVID-19 in red, influenza in blue, and RSV in green.

Weekly Hospitalization Rates (COVID-19, Influenza, RSV)

The inset, which shows rates since the beginning of the pandemic, is shown for context, and weekly rates for July 2023 through May 2025 are shown in the main graph. COVID-19-associated hospitalization rates peak both in the winter as well as the summer, as you can see with the large summer peak in the 2024 wave.

[1:01:03]
This differs from RSV and influenza, which generally have a similar peak.

Cumulative Hospitalization Rates

You can see the impact that this year-round circulation of SARS-CoV-2 has in this figure, which shows cumulative rates of COVID-19, influenza, and RSV-associated hospitalizations for the same period as the previous slide. Cumulative rates are the sum of consecutive weekly rates. For cumulative hospitalization slopes that are positive or increasing, that indicates ongoing new hospitalizations. For slopes that are flat, that indicates hospitalizations are minimal or slowed to zero. Cumulative rates of COVID-19-associated hospitalizations for the ongoing period of July 2024 through June 2025, shown in the solid red line, were higher during June to November, lower during November through June compared to those observed in the prior season from July 2023 to June 2024, shown with the dashed red line.

[1:02:12]
While cumulative rates of influenza-associated hospitalizations for the ongoing 24-25 season, shown in the solid blue line, are higher than rates for COVID-19-associated hospitalizations for the current season, they remain lower than last year's COVID-19 hospitalization rates. Note that surveillance for influenza-associated hospitalizations is limited to October through April, as that is a typical period of influenza circulation. While the remainder of this presentation will focus mainly on COVID-19 hospitalizations, note that different respiratory viruses affect age groups differently, with the biggest collective impact at the extremes.

Impact of Respiratory Viruses by Age Group

This figure shows cumulative rates of laboratory-confirmed hospitalizations for COVID-19 and influenza for July 2024 through April 2025.

[1:03:09]
More infants age less than one year and adults age 75 years and older had hospitalizations associated with COVID-19 than influenza during a high-severity influenza season.

Cumulative Rates by Age Group (<75)

On this slide, the larger figure shows cumulative rates of COVID-19 hospitalization by age group, with a focus on those less than 75. The rates of hospitalizations among infants less than six months are nearly identical to those age 65 to 74, with cumulative rates of 268 and 266 per 100,000, respectively. Similarly, rates among children age six to 23 months are nearly equal to those among adults age 50 to 64 months. The inset figure in the red box includes these same rates in addition to adults age 75 and older indicated in the orange line.

[1:04:14]
The next several slides will focus on the epidemiology of COVID-19-associated mortality.

COVID-19 Associated Mortality

The next three slides use data from the National Vital Statistics System that shows the number of death certificates coded with a specific code indicating COVID-19 as a cause of death.

National Vital Statistics System Data

Overall, COVID-19-associated deaths were currently decreasing and remain low this winter, lower this winter than they were in the summer and fall of 2024. This slide shows the number of deaths with COVID-19 listed as the underlying cause of death from July 2024 to June 2025 by age group. While COVID-19 causes deaths in all age groups, you can see that more than 70 percent of deaths occur in adults ages 65 and older.

Undercounting of Deaths

[1:05:06]
It is important to realize that the preceding two slides may substantially undercount the number of deaths due to COVID-19. Looking at data in COVIDNet, this figure shows the percentage of in-hospital deaths in patients hospitalized with laboratory-confirmed SARS-CoV-2 with COVID-19 as a cause of death listed on their death certificate.

In-Hospital Deaths in COVIDNet

The proportion of death certificates with COVID-19 as a cause of death has declined over time. The likelihood of having COVID-19 listed as a cause of death has decreased over time even among patients with COVID-19-associated hospitalization.

NCHS Provisional Death Certificate Data

Using provisional death certificate data, NCHS estimates that more than 20,000 COVID-19-related deaths occurred between October 2024 and May 2025.

[1:06:00]
And as discussed in the last slide, this is likely an underestimate.

CDC Estimated Deaths

Using additional data and modeling techniques, CDC estimates that since October 1, 2024, between 32,000 and 51,000 people have died in the U.S. from COVID-19. Next we'll turn to the epidemiology of COVID-19-associated hospitalizations.

Pediatric COVID-19 Associated Hospitalizations

This slide shows data from the New Vaccine Surveillance Network, which is a multi-pathogen enhanced surveillance network to assess pediatric viral respiratory and gastrointestinal infections and vaccine-impacting children.

New Vaccine Surveillance Network (NVSN) Data

These data compare hospitalization rates due to COVID-19 in red and influenza in blue from July 2024 through March 2025. Hospitalization rates for both viruses are highest for those younger than six months old and generally decrease with an increasing age through age 17.

[1:07:00]
For age groups younger than two, influenza and COVID-19-associated hospitalizations are similar. In those age two to 11 years, hospitalization rates were higher for influenza. And COVID-19 hospitalization rates for those ages 12 to 17 had too few detections and are not shown.

Percent of Hospitalizations by Pediatric Age Group

This figure from COVIDNet shows the percent of COVID-19-associated hospitalizations by age group by week from July 2024 through May 2025. For this period, hospitalizations among children younger than two years of age, shown in green, comprise 57% of all COVID-19-associated hospitalizations among children and adolescents, including infants younger than six months old who make up 27% of pediatric COVID-19-associated hospitalizations.

Severe Disease in Infants <6 Months

COVID-19 causes severe disease in infants younger than six months.

[1:08:00]
Infants have the highest rates of COVID-19-associated hospitalization among all pediatric age groups with rates comparable to adults 65 to 74 years. During July 2024 to May 2025, the COVID-19 cumulative, the COVID, the cumulative COVID-19-associated hospitalization rate among infants was 268 per 100,000, and the cumulative rate among adults age 65 to 74 was 266. Note, as indicated earlier in the presentation, rates are higher among those greater than 75.

Clinical Characteristics of Hospitalized Infants <6 Months

Among infants less than six months hospitalized recently for COVID-19, 22% were admitted to the ICU, 71% had no underlying medical conditions, and only 3.5% had any record of maternal COVID-19 vaccination during pregnancy.

[1:09:03]
No COVID-19 vaccine products are approved for infant ages younger than six months old. Any protection must come from maternal antibodies to the infant, either from vaccination during pregnancy or prior infection.

Vaccine-Eligible Infants and Older Children Hospitalizations

Transitioning to vaccine-eligible infants and older children, this figure shows the percent of weekly COVID-19-associated hospitalizations by age group from July 2024 through May 2025, limited to those children older than six months. Among them, children ages six to 23 months, shown in green, comprise 41% of all hospitalizations during July 2024 through May 2025.

Cumulative Rates Among Pediatric Age Groups

[1:10:01]
This figure shows cumulative rates among pediatric age groups from July 2024 through May 2025, and is similar to the one shown earlier. For reference, the younger than four age group is shown here as a dashed gray line. If you examine that rate line relative to the highlighted age subgroups, you'll see that rates of those age subgroups vary widely. While cumulative rates of the overall younger than four age group are 68 per 100,000, rates among infants younger than six months are 268, six to 23 months are 100, and two to four years are 22 per 100,000 population. This is the same figure as the previous one, but adding back in two adult age groups.

Comparison of Pediatric and Adult Hospitalization Rates

As previously mentioned, the rates of hospitalization among infants age younger than six months are nearly identical to those age 65 to 74.

[1:11:04]
Similarly, rates among children age six to 23 months are nearly identical to those among age to nearly equal to adults age 50 to 64 years.

Differences in Hospitalization Thresholds and Underlying Conditions

Additionally, there are differences among thresholds for admitting children and adults for hospitalization, which should be noted. As shown in the box, 94% of adults age 50 to 64 years hospitalized for COVID-19 had one or more underlying condition compared to only 46% of children age six to 23 months hospitalized for COVID-19. In other words, while most adults 50 to 64 years admitted for COVID-19 had underlying medical conditions, more than half of children six to 23 months were otherwise healthy before their COVID-19 hospitalization.

Clinical Characteristics by Pediatric Age Group

[1:12:01]
Not only do hospitalization rates vary by pediatric age group, but the clinical characteristics, including underlying medical conditions of infants, children, and adolescents being hospitalized for COVID-19 also differed by age group during recent seasons. This slide shows the proportion of children hospitalized for COVID-19 who did not have any underlying medical conditions.

Proportion of Hospitalized Children with No Underlying Conditions

54% or more than half of children age six to 23 months hospitalized for COVID-19 had no underlying medical conditions. Among those with an underlying condition, the most common condition was prematurity. Among the three older pediatric age groups, those aged two to 17 years, more than 70% of children and adolescents had at least one underlying condition with asthma and reactive airway disease and neurologic disorders being the most common conditions.

Underlying Conditions in Older Pediatric Age Groups

The proportion of hospitalized children with no underlying medical conditions decreases with age.

[1:13:02]
Among children who are hospitalized for COVID-19, many continue to experience severe outcomes.

Severe Outcomes Among Hospitalized Children

From April 2024 to March 2025 overall, 24% of children younger than 18 years were admitted to the intensive care unit. This is consistent across all age groups. As indicated in the red bracket, 23% under two years were admitted to the ICU during hospitalization for COVID-19. Among them, 53% had no underlying medical conditions, although this varied by age group. This slide shows that the majority of children hospitalized for COVID-19 during October 2024 to March 2025 did not receive the most recently recommended COVID-19 vaccine.

Vaccination Status of Hospitalized Children

Roughly 10% of children across all vaccine eligible pediatric age groups have received the recommended COVID-19 24, 25 dose.

Pediatric Mortality

[1:14:02]
Next, we will turn to pediatric mortality. This is slide 28. Okay, we're good. This graph shows the number of documented COVID-19 and influenza deaths among people ages zero to 17 years from July 2024 to June 2025.

COVID-19 and Influenza Deaths Among Children

For children younger than two, the number of deaths associated with COVID-19 in red was similar to the number of deaths associated with flu shown in blue. However, for children ages two to 17 years, there are more deaths associated with influenza than COVID-19.

[1:15:02]
It is important to note that COVID-19 deaths here are likely an underestimate because pediatric deaths associated with influenza are nationally notifiable, but pediatric deaths associated with COVID-19 were not during this time period.

Undercounting of COVID-19 Pediatric Deaths

Since March 2020, 128 deaths among children and adolescents occurred among residents of the COVID-19 catchment area, either during COVID-19 associated hospitalization or within 30 days after discharge.

Deaths in COVID-19 Catchment Area

Of the 25 who died in the catchment area since July 2023, 10 occurred during the past 12-month period of April 2024 through March 2025. Please note that these are raw counts and that COVID-19 catchment area represents about 10% of the U.S. population.

[1:16:00]
Among those 25 pediatric deaths since July 2025, 52% were younger than age two years, 72% had at least one underlying condition. Of the 16 who were age eligible for COVID-19 vaccination, 14 had no record of COVID-19 vaccination, and none were up to date.

Reporting Delays and Death Certificate Data

Reporting for death certificate data to RestNet are delayed. Data from 2022-2023, the most recent available data for the complete death certificate. Among those, the 25 most recent deaths for which we have complete mortality data, 28% had COVID-19 as a specific cause of death on their death certificate. An additional nine had causes of death attributed to other respiratory circulatory causes. As previously mentioned, death certificate data alone might underestimate COVID-19 associated pediatric deaths.

Summary of Pediatric Data

[1:17:04]
In summary, most pediatric hospitalizations occur in children younger than two years. Most of these hospitalized children have no underlying medical conditions, including 71% of infants ages less than six months old and half of children age six to 23 months. Rates of COVID-19 associated hospitalizations are the highest among infants aged younger than six months, followed by those six to 23 months. Rates of COVID-19 associated hospitalizations among infants younger than six months are comparable to rates among older adults age 65 to 74 years. Notably, no COVID-19 vaccine products are approved for the youngest infants under six months. Any protection for them must come from transfer of maternal antibodies, either through vaccination during pregnancy or prior infection. Outcomes among hospitalized children can be severe, with one in four admitted to the intensive care unit.

[1:18:03]
COVID-19 deaths continue to occur among infants and children. The majority of COVID-19 vaccine eligible children and adolescents who were hospitalized had no recent record of receiving the most recently recommended vaccine.

Adult COVID-19 Associated Hospitalizations

On to COVID-19 associated hospitalizations in adults. As noted previously, adults comprise the vast majority of COVID-19 associated hospitalizations, with older adults being the most impacted, and rates are highest among adults age 75 years and older.

Hospitalizations by Adult Age Group

This figure shows the weekly percent of COVID-19 associated hospitalizations by adult age group from March 2024 through May 2025.

[1:19:01]
For this period, July 2024 through May 2025, highlighted in the red box, adults ages 65 and older comprise 72 percent of all adult COVID-19 associated hospitalizations captured in the COVID net. Adults 75 years and older comprise half of all COVID-19 hospitalizations among adults, despite making up less than 10 percent of the population. This figure shows the number of underlying medical conditions reported among adults hospitalized for COVID-19.

Underlying Medical Conditions in Hospitalized Adults

Most adults hospitalized with COVID-19 had at least one underlying medical condition. Majority had two or more underlying medical conditions. Even among the youngest adults, those ages 18 through 49 years, shown in light green, the prevalence of one or more underlying medical conditions is 86 percent, with 61 percent having two or more underlying medical conditions.

[1:20:00]
A significant proportion of adults hospitalized for COVID-19 experienced severe outcomes, with the proportion experiencing ICU admission shown in tan, invasive mechanical ventilation in blue, and in-hospital death in red.

Severe Outcomes Among Hospitalized Adults

Overall, 15 percent of adults hospitalized for COVID-19 were admitted to the ICU. In-hospital death is more common among adults 50 years of age and older. As noted in the yellow box, during this period, 85 percent of all adults hospitalized for COVID-19 who died in hospital were ages 65 years and older. Note that these are only in-hospital deaths. This slide shows the proportion of adults hospitalized for COVID-19 by vaccination status among adult age groups for October 2024 through March 2025.

Vaccination Status of Hospitalized Adults

[1:21:09]
Among adults 65 years and older, highlighted in the box on the far right, 65 percent of adults hospitalized for COVID-19 received neither the 2023-24 or 24-25 formula COVID-19 vaccine. One-third of adults age 65 years and older hospitalized for COVID-19 received the recommended at least one dose of the 24-25 vaccine prior to admission. 17 percent received two doses.

COVID-19 Associated Hospitalizations Among Pregnant Women

On to COVID-19-associated hospitalizations among pregnant women. In COVIDNet, pregnancy status was collected from SARS-CoV-2 positive hospitalized women ages 15 to 49 years. 28.5 percent of women aged 15 to 49 years hospitalized with laboratory-confirmed SARS-CoV-2 infection were pregnant.

[1:22:05]
Fifty percent of those had COVID-19-related signs or symptoms. Among 131 hospitalized pregnant women with a laboratory-confirmed SARS-CoV-2 positive test result and underlying COVID-19-related signs or symptoms, and COVID-19-related signs or symptoms, 50 percent had no underlying conditions. 68 percent were no longer pregnant at discharge, among whom 83 percent had a healthy newborn, 11 percent had a preterm infant, 1 percent had an infant, and 5 percent had pregnancy loss. 92 percent had no record of COVID-19 vaccination since July 1st, 2023. 5.8 percent received recommended 24-25 COVID-19 vaccine dose.

[1:23:02]
To summarize the adult data, rates of COVID-19-associated hospitalization are highest among oldest adult age groups.

Summary of Adult Data

Adults age greater than 65 comprise 72 percent of adult COVID-19-associated hospitalizations, and those 75 years and older comprise 50 percent of adult hospitalizations. COVID-19-associated hospitalizations have decreased over time, but cumulative rates among adults age greater than 75 years remain high. The risk of COVID-19-associated hospitalization continues year-round, peaking in winter and summer months. 65 percent of adults age 65 years or older hospitalized with COVID-19 had no record of receiving greater than one dose of the recommended 24-25 COVID-19 vaccine prior to hospitalization. Most adults hospitalized for COVID-19 have at most had two.

[1:24:01]
Among SARS-CoV-2 positive pregnant women admitted during April 24 to March 2025 with COVID-19-related symptoms on admission, 50 percent had no underlying medical conditions, and most, 92 percent, had no record of COVID-19 vaccination since July 1st, 2023.

SARS-CoV-2 Genomics

Next, we'll transition to SARS-CoV-2 genomics.

Viral Evolution and Spike Protein Changes

Since SARS-CoV-2 emerged in late 2019, we observed evolution of the viruses with accumulating substitutions in the spike protein, which binds the H2 cellular receptor and is target for neutralizing antibodies. Looking at this timeline along the x-axis and looking at the timeline along the x-axis and number of spike protein amino acid differences on the y-axis, you can observe periods of both drift and accumulations of changes and shift when new lineage is emerged and had numerous changes.

Periods of Drift and Shift

[1:25:09]
So, really important stuff here. The first time we observed a shift was in late 2021 to 2022, and you can see by the jump from purple to orange dots. That was the shift from Delta to Omicron. We have also observed shifts from BA.45 viruses to XBB viruses, and then from XBB to JN.1 viruses. These shifts necessitated changing the formulation of the COVID-19 vaccine dose.

Strain Replacement and Vaccine Formulation

The 23-24 formulation of the COVID-19 vaccine that was released in fall of 2023 was XBB.1.5. During the winter, we observed circulation of XBB.1.5 sublineages like EG5, FL1.5.1, and HV1, which were very similar to XBB.1.5. December 2023 to January 2024, we observed a strain replacement of XBB.1.5 to JN.1 viruses, which evolved independently of XBB.1.5 viruses.

[1:26:22]
Since the emergence of JN.1, SARS-CoV lineages have continued to evolve from JN.1, and we've not observed a strain replacement.

JN.1 Lineage Predominance

All the lineages that have predominated since the JN.1 emergence are descendants currently of JN.1. Viruses that have predominated since January 2025, as noted, are all JN.1 descendants. I circled the JN.1 lineage in this dendogram in each sublineage that has predominated in the last 1.5 years. We continue to see JN.1 lineage viruses predominating. This was the weighted and now-cast estimates posted on COVID Data Tracker on June 10, 2025.

[1:27:07]
LP.8.1 was a predominant lineage through the spring, though now NB.1.8.1 appears to be increasing in proportion, as well as XFG and XFC. All of these are still JN.1 lineage viruses. As mentioned, LP.8.1, XFC, and NB.1.8.1 are JN.1 lineage viruses.

Amino Acid Alignment and Changes

This is an amino acid alignment of substitutions in the spike protein in comparison to the 24-25 COVID-19 vaccine formulation. There are only two to four changes in the receptor binding domain in comparison to last year's vaccine. As a reminder, last summer, circulating viruses had 13 or more changes in spike receptor binding domain in comparison to the vaccine formulation.

[1:28:03]
So for time, I'm going to skip over the slide that has sera.

Skipping Sera and Antigen Cartography Slides

This was presented recently at the VRBPAC meeting, as well as the antigen cartography. The big picture is that the current circulating lineages appear relatively similar structurally wise to those in vaccine formulations.

Summary of COVID-19 Genomics

To summarize the COVID-19 genomics, current viruses are JN.1 descendants with two to three substitutions in spike receptor binding in the spike receptor binding domain in comparison to KP2 spike. Current viruses are neutralized with sera from participants who received the 24-25 COVID-19 vaccine. Antigenic cartography indicates JN.1 viruses are similar. FDA's VRBPAC reviewed genomic and phenotypic data in May 2025 and unanimously voted to recommend a monovalent JN.1 lineage vaccine as its composition.

[1:29:04]
FDA has advised manufacturers to use JN.1-based COVID-19 preferentially using the LP8.1 strain for the 25-26 COVID-19 vaccines. I'll now move on to discussing COVID-19 vaccine effectiveness.

COVID-19 Vaccine Effectiveness Presentation

This is the next set of slides, please.
[Dr. Mina Zadeh]
Thank you. I think we're going to continue with the presentations, and the next presentation is on COVID-19 vaccine effectiveness. Dr. McNeil.
[Ben Spader]
Sorry. Go ahead. Okay. I will now move on to presenting COVID-19 vaccine effectiveness.

[1:30:03]
I'll start today with methods and context for how we measure and interpret vaccine effectiveness, or VE, and then present estimates of COVID-19 VE in children and adults, and overall conclusions.

Methods and Context for VE Measurement

I'll start by summarizing VE methods and providing some context for interpretation of results. For respiratory viruses, CDC generally uses a case control design, often the test negative design, or TND, to measure vaccine effectiveness.

Test Negative Design (TND)

In the TND, people who seek care for respiratory illness are included. Cases are those that test positive for SARS-CoV-2, and controls are those that test negative. Controls in these studies are meant to represent the population from which the cases arose, and here give us an understanding of COVID-19 vaccine coverage among people seeking care for respiratory illness.

[1:31:06]
We then compare vaccination status in cases and controls to determine vaccine effectiveness, or VE. If coverage is higher among controls than among cases, that indicates the vaccines are associated with protection against disease. Because both cases and controls are people seeking care for respiratory illness, we can reduce the impact of factors that can distort or confound the relationship between vaccination status and illness. Reducing the impact or adjusting for factors like age and geography helps to make the true relationship between vaccination status and illness clear.

CDC Platforms for VE Assessment

Today, I'll be sharing VE results from three CDC platforms for children and adults. The first VE platform is the Vision Network, a multi-site network of over 200 electronic health records, a multi-site network of electronic health records at over 300 emergency departments and urgent care clinics and over 200 hospitals that include both children and adults.

Vision Network

[1:32:15]
Vision uses a test negative design and includes eligible people of all ages with COVID-19-like illness and a clinical test within 10 days before or 72 hours after their encounter. Cases are those with a positive NAT or antigen test for SARS-CoV-2 and no positive RSV or influenza test result. Controls are those with a negative NAT test for SARS-CoV-2 and no positive NAT test result for influenza or RSV, depending on age. Vaccination is documented by electronic health records and state or city registries. The second VE platform enrolls only children with enrollment at 26 pediatric hospitals in 20 states.

Pediatric Hospitalization Platform

[1:33:04]
The analysis I'll present today for this platform is designed to assess the effectiveness of COVID-19 vaccination in pregnant women for prevention of COVID-19-related hospitalizations in infants less than six months of age.

IVY Network

The third platform included today is the IVY network, a multi-site VE platform in 26 hospitals in 20 states that, like Vision, uses a test negative design. Unlike Vision, IVY uses an active enrollment design with patient interviews and nasal swabbing of enrollees. Participants included in analyses presented today were adults ages 18 and greater, years, hospitalized with COVID-19-like illness. Cases have a SARS-CoV-2 positive nucleic antigen test or antigen or nucleic acid test or antigen test and controls were negative for SARS-CoV-2 influenza and RSV by RT-PCR.

[1:34:03]
Vaccination history is ascertained through electronic medical records, state and local vaccine registries, and plausible self-report and specimens are collected for central testing and sequencing.

Changes in VE Measurement Approaches

Here we've measured COVID-19 VE. Here's how COVID-19 VE measurements have been changed in terms of approaches by season. When COVID-19 vaccines were first released, we measured absolute VE, which compares the frequency of health outcomes in vaccinated versus unvaccinated people. During the bivalent era, however, we also measured relative VE, which compares the frequency of health outcomes in people who received one type of vaccine to people who received a different vaccine. For example, people who received a bivalent vaccine versus those who received only the original monovalent COVID-19 vaccine. Generally, for 2023-24 and 24-25 COVID-19 vaccines, we've combined absolute and relative VE and measured protection as a frequency in disease in those who received the current vaccine to those who did not, regardless of their past vaccination or infection history.

[1:35:18]
In other words, the comparison group for the 2023-24 VE analysis includes people who are unvaccinated as well as those who received original monovalent and bivalent COVID-19 doses. The same is true for the 24-25 estimates, where the comparison group is people who are unvaccinated or received original monovalent, bivalent, or 23-24 COVID-19 vaccines.

Similarity to Influenza VE Measurement

Of note, this is similar to how influenza vaccine effectiveness is measured each year. This represents the added benefit of a seasonal vaccination for the respective season, regardless of previous vaccination or infection history.

COVID-19 Vaccination Coverage in Children

[1:36:04]
This graph shows the COVID-19 vaccination coverage from CDC's National Immunization Survey during the 23-24 and 24-25 seasons among children aged six months to four years in blue and among children and adolescents aged five to 17 years in green. 23-24 uptake is shown in dotted lines and 24-25 uptake is shown in solid lines. You can see that coverage was similar in both years, remained quite low, the lowest coverage in youngest children occurred during the 24-25 season.

COVID-19 Vaccination Coverage in Adults

Here we see data on uptake of COVID-19 vaccines among adults aged 18 years and up, with the 23-24 shown in blue and 24-25 shown in gray. Note that the 24-25 vaccines were recommended a few weeks earlier than the 23-24 vaccines, so coverage started to increase a bit earlier, but ended up similar at just under 25% during each spring year.

Coverage Among Older Adults by Underlying Condition

[1:37:13]
Moving on to older adults, this slide uses data from Medicare fee-for-service beneficiaries aged 65 years and older to understand coverage for the 24-25 COVID-19 season by underlying medical condition status. The x-axis is calendar week and two-week periods and the y-axis is coverage. You can see in red the overall coverage was 28% for this group by January 2025. Coverage was highest among those with immunocompromising conditions at 32%, the lowest among those with no underlying medical conditions at 24%.

COVID-19 VE in Children

I'll now share estimates for COVID-19 VE in children.

Cumulative Hospitalization Rates in Children

[1:38:02]
This graph from CDC's COVIDNet surveillance platform shows cumulative rates of COVID-19 hospitalizations for 23-24 and 24-25. As the coverage graphs, as with coverage graphs, younger kids are again in blue and older kids are in green with 23-24 rates in the dotted lines and 24-25 rates in the solid lines. You can see that rates are higher in the younger children and that rates in the 24-25 season were lower in both age groups than in 23-24. As you'll see, this results in less statistical power for 24-25 analyses. It means that we are able to share, means that we are only able to share data for final stratifications for 23-24. This slide shows the 23-24 COVID-19 vaccine effectiveness against emergency department and urgent care encounters, including data through August 24, which is when the 24-25 vaccines were released.

23-24 COVID-19 VE Against ED and Urgent Care Encounters

[1:39:09]
Note that the reference group includes all individuals who did not receive a 23-24 COVID-19 vaccine. For those aged greater than five years, this includes unvaccinated persons and persons who were vaccinated with greater than one original monovalent or bivalent COVID-19 doses. For those aged less than five years, both those in the reference group and those in the vaccinated group were required to have completed an initial series. The 23-24 dose could have been part of the initial series or in addition to the initial series. In the top block, you see counts of encounters, cases, and time since dose for people who did not receive a 23-24 COVID-19 by age group, nine months to four years, five to 17 years, and adults 18 and up. The middle block shows VE among those who received a 23-24 dose seven to 59 days earlier, and the bottom is VE among those who received 23-24 dose 62 to 299 days earlier.

[1:40:16]
Note that there was not enough children vaccinated from days 60 to 299 with positive SARS-CoV-2 tests to split the 60 to 299 day block in children with more granularity. You can see that VE is estimated to be as good or better among children as it is among adults. This aligns with previous seasons showing generally comparable VE across age groups. This slide is similar to the previous one, though now showing VE during the 24-25 season.

24-25 COVID-19 VE Against ED and Urgent Care Encounters

As mentioned, lower numbers of COVID-19 cases in 24-25 resulted in less statistical power during the season, so we're not able to estimate VE by time since dose for 24-25.

[1:41:09]
Instead, we've shown overall VE for the seven to 179 days since receipt of a 24-25 COVID-19 vaccine dose. You can see that as with 20-23, 24, VE is the same or higher in children and adults.

Effectiveness of Maternal COVID-19 Vaccine for Infant Protection

Now we'll move on to estimates of effectiveness of maternal COVID-19 vaccine receipt for protection of COVID-19 associated hospitalization among infants from the overcoming COVID-19 network during 2022-2023. Maternal VE is particularly important because infants under six months of age are not eligible for COVID-19 vaccination and have higher rates of severe COVID-19 disease than older children and most adult age groups.

[1:42:02]
Vaccination of pregnant women is the only way to protect their infants from severe disease. This analysis included mothers who received their last dose of COVID-19 mRNA vaccine between the first day of pregnancy and 14 days before delivery. The comparison group was mothers who did not receive any COVID-19 vaccination either before or during pregnancy. As you can see, VE was highest in the youngest children at 54% during the first two months of life and 35% during the first zero to five months of life. This mirrors patterns in older children and adults where VE drops with more time since dose.

VE Drops with Time Since Dose

I'll now share results for COVID-19 VE in adults.

COVID-19 VE in Adults

Absolute VE of Older Doses in Pregnant Women

[1:43:11]
This slide shows absolute VE of original monovalent and bivalent doses received prior to or during pregnancy against COVID-19 associated emergency department or urgent care visits in pregnant women aged 18 to 45 years. Note that although these are older vaccines, the data were collected during 2023 and during 2022 and 2023 when Omicron was the dominant variant. As you can see, a dose during pregnancy in this population administered a median of 91 days before the encounter provided 52% protection while a dose administered less than six months before pregnancy a median of 267 days from the encounter yielded 28% protection and a dose six months or more was not statistically different than zero.

[1:44:04]
This follows the pattern we see in non-pregnant adults and children where more recent dose gives the highest protection.

23-24 Monovalent VE in Pregnant Women

This slide shows similar data now for 23-24 monovalent COVID-19 vaccines. Although there was not statistical power here to look at the time since dose, we can see that protection in pregnant women a median 77 days after COVID-19 vaccination shown on the top was similar to protection in non-pregnant women of the same age group, a median of 83 days after COVID-19 vaccination.

Characteristics of Patient Populations for Adult Analyses

This slide shows the characteristics of the patient populations included in the next analysis I'll present. First, above the top you see each of the three analyses, vision emergency department urgent care encounters in adults aged 18 years and up, vision hospitalizations in adults aged 65 and up, which include estimates against critical illness, and IV hospitalizations in adults aged 65 years and up.

[1:45:11]
First, you can see that median age for the emergency department urgent care encounters was low, in the low to mid-50s compared to hospitalization analyses in both platforms, which had median ages in the mid to high 70s. Keep in mind that the only analysis we'll share today that included adults aged 18 to 64 was the vision ED urgent care analysis. Younger adults were excluded from hospitalization analyses for both vision and IV because of lack of statistical power due both to lower baseline hospitalization rates and lower COVID-19 vaccine uptake in younger adults. However, we've seen in previous seasons that VE is similar among those aged 18 to 64 and those aged 65 and up.

[1:46:01]
Finally, both platforms include VE for adults with immunocompromising conditions. This slide shows VE of the 24-25 COVID-19 vaccines against COVID-19 associated emergency department and urgent care encounters by age group.

24-25 COVID-19 VE Against ED and Urgent Care Encounters in Adults

The top block shows VE for all adults aged 18 and up during the 7 to 179 days after the dose and split by time since dose. 7 to 59 days, 60 to 119, and 120 to 179 days. The middle block shows the same information for adults aged 18 to 64 years and adults aged 65 years and up. The first column shows COVID-19 cases. The second column shows COVID-19 controls. The third column shows median time since the last dose among vaccinated.

[1:47:01]
And then finally, the last column of forest plot shows vaccine effectiveness. Note that among the reference group, those who did not receive the 24-25 COVID-19 vaccine, it's been a medium of around 1,000 days or almost three years since we received the last COVID-19 vaccine dose for all adults. VE among all adults aged VE among all adults against COVID-19 associated emergency department and urgent care encounters was 34% for the 7 to 179 days since receipt of a dose, 36% for the 7 to 59 days, 35% for the 60 to 119 days, and 28% for the 120 to 179 days since a 24-25 COVID-19 vaccine dose. VE among younger and older adults was similar.

[1:48:14]
This slide shows VE against COVID-19 associated hospitalization.

VE Against COVID-19 Associated Hospitalization in Older Adults

Among adults aged 65 years and up without documented immunocompromising conditions in the vision and IV networks. This slide is laid out the same as the previous slide, except instead of age groups, it shows vision adults in the top block and IV results in the bottom block for adults aged 65 years and up. VE was almost identical across the two networks, providing reassurance of the results. During the 7 to 179 days since the dose, the point estimate was 44% in vision and 46% in IV. VE started at 46% in vision and 42% in IV, declining to 32% in vision and 40% in IV during the 120 days after vaccination.

[1:49:07]
Although note that the confidence intervals for this time period are wider due to smaller numbers of both cases and controls vaccinated four to six months before their encounter.

VE Against COVID-19 Associated Critical Illness

This slide shows VE against COVID-19 associated critical illness in vision and IV. Vision on the top defines critical illness as admission to intensive care or in-hospital death, and estimates are shown by time since dose among those 65 years and up. You can see that point estimates do not change much over time, even in the longest time since dose strata, 120 to 179 days since the dose, indicating relatively durable protection.

[1:50:01]
This mirrors what we've seen in previous years. VE against the most severe outcomes remains the most durable over time, with little evidence of waning in the longest time since dose period. In IV, shown on the bottom, we have VE against three separate outcomes, all shown for the 7 to 179 days since the dose, shown generally by increasing severity, including acute respiratory failure, ICU admission or death, and invasive mechanical ventilation. Here, again, we see indications of higher VE for the most severe outcomes, at 70% for invasive mechanical ventilation or death.

VE Against Hospitalizations in Immunocompromised Adults

This slide shows VE against COVID-19 associated hospitalizations among adults aged 65 years and up with immunocompromising conditions in vision and IV, though IV did not have enough statistical power to estimate VE by time since dose in this group.

[1:51:09]
In vision, VE appears to be increasing over time, which is something we've seen previously in adults with immunocompromising conditions, and is likely due to faster waning of infection-induced immunity in immunocompromised people, which would make the referent group, those who did not receive a 24-25 vaccine, have less protection over time since the summer surge, thereby appearing to increase VE. VE for the overall time period, 38% in vision and 36% in IV, is close to VE in non-immunocompromising adults, providing assurance that vaccine is working in immunocompromised adults.

VE by Strain from IV Network

I'll next share VE by strain from the IV network. In this sub-analysis, IV conducted whole genome sequencing and restricted to patients with sequence-confirmed KP3.1.1 or XCC lineage viruses and calculated VE against hospitalization separately for each lineage.

[1:52:10]
As with the main analysis, controls were those with COVID-like illness and tests, negative tests for SARS-CoV-2, influenza, and RSV. This slide shows the VE, this slide shows the results of the VE by lineage analysis with KP3.1.1 on the top and XCC on the bottom. You can see that VE was similar across lineages with largely overlapping confidence intervals. Note that median time since dose for KP3.1.1 cases who had received a 24-25 dose was 56 days, while the median time since dose for the XCC cases who had received a 24-25 dose was 87 days, likely accounting for the slightly different point estimates, 45% for KP3.1.1 and 34% for XCC.

Summary of Vaccine Effectiveness Findings

[1:53:08]
For the respective year compared to no in-season COVID-19 vaccination, for this respective year compared to no in-season dose, COVID-19 vaccination provided additional protection from COVID-19-associated emergency department and urgent care visits among children, projection was generally similar across all these age groups, COVID-19-associated emergency department and urgent care visits among adults, COVID-19-associated hospitalizations among adults age 65 years with and without immunocompromising conditions, and COVID-19-associated critical illness among adults age 65 years and older. Protection appeared to be higher and more durable against more critical illness compared to less severe outcomes. VE should be interpreted as the added benefit of the 23-24 or the 24-25 COVID vaccination in a population with high levels of infection-induced immunity, vaccine-induced immunity and both.

[1:54:09]
Prior to SARS-CoV-2 infection contributes protection against future disease, though protection like with vaccination wanes over time.

Interpretation of VE in a Population with High Immunity

An increase in SARS-CoV-2 circulation in the United States occurred in late summer 2024, just before the 24-25 COVID-19 vaccines were approved and authorized. This may have resulted in a higher proportion of population-level immunity against J and 1 lineage strains, which could have resulted in lower VE measured than in a population with less recent infection. I'd like to thank the numerous colleagues from CDC and collaborators with vision, IV and overcoming networks who contributed to this presentation.

Acknowledgments

I'll now hand it off to Captain Meyer, who will present on vaccine safety.

[1:55:01]
Thank you.
[Dr. Martin Kulldorff]
Thank you, Dr. McNeil.

Questions from Committee Members

Before we go to the next presenter, we're going to take some questions from committee members. And I'm going to use my privilege as chair to ask the first question.

Question on Randomized Controlled Trials

I really appreciate that you emphasize hospitalizations and death because that's really what matters when it comes to COVID. The gold standard of medical research or the randomized placebo-controlled trials, double-blind, what are the results in terms of vaccine efficacy from such randomized trials?
[Ben Spader]
So, I'm also going to look to my SMEs here to comment. But I think it's also important to remember a lot of the randomized controlled trials were done in largely naive populations.

[1:56:00]
And what we're looking at in these couple of recent years is basically the added value in a population that's had multiple exposures to vaccines or infection. So, randomized clinical controlled trials are not necessarily comparable to what we're currently seeing with the vaccine. And, you know, we've seen across these different ages, we're seeing ballpark that the added benefit is in the range of 30 to 50%. So, it's, you know, I think it's where we're trying to now monitor is the world impact of these vaccines as opposed to clinical trial data, which was certainly extensively documented.
[Dr. Martin Kulldorff]
And in terms of observational studies, it's important that the control group is sort of a representative of the population at large.

Question on Observational Studies and Test Negative Design

And that's usually best accomplished with the cohort study. If doing a case control study, the best thing is to recruit the controls from the general population.

[1:57:07]
And that's a weakness for the test negative design because the control group are people who have a different type of infection that's not COVID. And that's just been a very special, peculiar population, which might have very different vaccination patterns. Were most of the results from the test negative design or were they also some of the results from cohort studies or traditional standard case control studies?
[Ben Spader]
Yeah. No, it's a good question. So, I think it's, you know, case control has some limitations in comparison to your classic cohort type study. These platforms all rely on case control design, a majority of test negative design.

[1:58:00]
And much of this is the ability for us to have efficiency to be able to collect data in large populations in such a way that is not cost prohibited. So, and as we get up to substantial numbers in these study designs, it's able to generate a relatively accurate estimate of the VE, so.
[Dr. Martin Kulldorff]
Thank you. And we'll go to the next. I think we have Dr. Cody Meyer wanted to ask some questions remotely, and then we'll go to the people in the room here.

Question from Dr. Cody Meissner on Hospitalization Definition

[Dr. Cody Meissner]
Yes. Thank you, Dr. Kilgore. Cody Meissner here. First, I'd like to recognize the enormous amount of work that was provided by the CDC, many people in generating this data that has been so helpful in understanding the pandemic.

[1:59:05]
I think they oftentimes go unrecognized and I and many others appreciate it. I also want to thank Dr. McNeil for presenting a huge amount of data in a short period of time, a very difficult task, and you deserve a promotion for presenting that so clearly and effectively.
[Ben Spader]
I'm going to interrupt you and look over to Dimitri with a little nod right there.
[Dr. Cody Meissner]
Thank you. Sorry, back to you, Dr. Meissner. It's a Herculean task and you did it very, very well. But I've got a series of questions and I'm going to try and focus on the most important ones, I think, that apply to everything. First of all, you used, you referred to the COVID hospitalization rates in numerous slides and I assume the COVID hospitalization rate refers to a hospitalized person who has a positive RT-PCR assay for COVID.

[2:00:23]
That doesn't mean a person is hospitalized because of COVID. And it's a patient who's hospitalized with COVID in the pharynx. And those are two very different things. The Commonwealth of Massachusetts did a study, they've discontinued it, but they used to look for how many patients who had a positive PCR assay were actually being treated for COVID and it turned out that less than half of them were. So I think many of the numbers that have been presented may not really reflect COVID hospitalization.

[2:01:09]
People may have been hospitalized because of appendicitis, for example, and happen to have a positive PCR result because we know that asymptomatic colonization is quite common with this virus. So first of all, I'll ask you, and I'll stop there. If Dr. Kildorf will permit, I have some other questions, but I'm interested in your response to that. Over.

Response on Hospitalization Definition and Clinical Data Filtering

[Ben Spader]
Yeah, I'm, if you give me one second, we have, you know, this has certainly been a very commonly discussed question and we certainly looked at it in detail. I'm going to look at, see, I have a number of SMEs on the line. I wonder if I can have someone jump in real quickly while I'm looking through our data.

Comment on Pregnant Women Hospitalizations

[Dr. Cody Meissner]

[2:02:04]
I will also just comment while you're looking. I think you said that 50% of the pregnant women who were hospitalized had signs and symptoms of a respiratory infection. So I interpret that to mean the other 50% did not have signs and symptoms and were therefore colonized, if that's the right word, with this coronavirus.
[Ben Spader]
Meena, are we able to jump over to our SME line?
[Dimitri Daskalakis]
We should have an SME online who knows. We do have an SME who's trying to chime in. So if that line could be turned on, that would be great.
[Dr. Christopher Taylor]

[2:03:01]
Hi, can you hear me?
[Speaker 31]
Yes.

SME Response on COVID-NET Data and Attributable Hospitalizations

[Dr. Christopher Taylor]
Hi, my name is Dr. Christopher Taylor and I'm an SME with the COVID-NET system. And that's an excellent question you asked, Dr. Meisner, and thank you for allowing me to address it. There are two sort of components to the COVID-NET data that were presented, the population-based rates of COVID-19-associated hospitalization and the clinical data that's based on a sample of those hospitalizations. The rates that are presented, again, are population-based rates, and as you correctly said, are based on lab-confirmed SARS-CoV-2 positive tests. The clinical data that we present are limited to a sample and that sample is further filtered and the results, and you'll note if you go back into the slides on the footnotes, those results are limited to those where COVID-19 was identified as the likely reason for admission for those hospitalizations.

[2:04:06]
A few months ago, we published a peer-reviewed paper in influenza and other respiratory viruses looking at the trends in COVID-19 attributable hospitalizations among adults with lab-confirmed SARS-CoV-2. And what we found was that looking, again, just at adults 18 years of age and older, 86% of hospitalizations during the most recent period, which for that manuscript includes 2022 and 22-23, 86% of populations we could define as COVID attributable, which includes cases that were identified as having a reason for admission likely attributable to COVID-19, meaning that it was identified that they had COVID-19-related illness on admission. They received a course of medicine during their hospitalization for persons with severe disease among hospitalized persons with COVID-19, or they had a select subset of discharge diagnoses related to outcomes of COVID-19, such as pneumonia or ARDS or something like that.

[2:05:16]
So again, we found 86% of adult hospitalizations during that time period were somehow attributable to COVID-19.

Follow-up Question on Severity Decrease and Death Definition

[Dr. Cody Meissner]
Well, thank you for that very helpful information. I guess my only response is that the severity of disease due to COVID has decreased since, I think you said, 22-23. We know that there are many fewer hospitalizations now than there were then. Whether that reflects mutations in the virus that lead to less severe disease, or whether we all have a baseline immunity from the vaccine and or infection, I guess is a hard question to answer, but thank you for that answer.

[2:06:12]
I guess it would also apply to the question of death due to SARS COVID-2. How many of the deaths occurred people who had respiratory symptoms or other symptoms referral to a viral infection, and how many simply had a positive throat swab? Because many hospitals have required a throat swab on anybody who's admitted and then classified as SARS infection.

Response on Death Analysis and Screening Practices

[Dr. Christopher Taylor]
Yes, thank you. That's an excellent question, and we actually have an ongoing analysis looking at deaths. We're compiling the most recent years of death certificate data, and we're actually in the sort of the mid-stages of that now, and we hope to present it to ACIP when we have findings in the future.

[2:07:09]
One thing I would also note, too, about the COVID hospitalizations is one of the things that we knew early on in the pandemic was everyone being presented to a hospital was being screened for COVID, and we know that that is no longer necessarily the practice in most hospitals. So what we have seen, at least preliminarily with the 21, 22, and 22, 23 data in our published COVID hospitalization paper is that the proportion of hospitalizations attributable to COVID has actually increased slightly over time, likely as a result of decreased screening. So the number of asymptomatic people being screened has decreased, so the people that are being tested for COVID-19 are more likely to be those that come in and have some sort of symptom of COVID-19-related illness.
[Dr. Martin Kulldorff]

[2:08:05]
Dr. Meissner, you said you had one more question?

Question on Hospitalization Rates in Young Children

[Dr. Cody Meissner]
I've got, all right, let me ask, okay, a quick point I want to make is that looking at the most recent CDC data on hospitalization rates among children 0 to 4 years of age, it's less than 1 hospitalization per 100,000 children, and I think that even if we look at children under six months of age, looking at that same table, it's 1.6 hospitalizations per 100,000. Is that a correct interpretation? So my point is this is a very rare illness in young children, as well as in adults now.

Response on Cumulative Numbers and Burden

[Ben Spader]

[2:09:08]
I mean, I would also just make sure we also think and point to overall cumulative numbers that there are, you know, cumulative numbers, this does remain a substantial burden, particularly among the youngest and oldest age groups. To me, I think some of the comparisons to influenza, if you go back through the slides, are, I think, quite telling that there are still areas for concern with COVID-19.
[Dr. Cody Meissner]
Okay, but are those, do you think those rates are accurate?

Comment on Comparison with Influenza

[Ben Spader]
Yeah, so the rates from COVID-NET has been, you know, really a very robust platform that captured, it's captured about 10% of the U.S. population, allows very well characterization of illness.

[2:10:09]
So, and then, you know, from there are modeled rates to the entire country. Obviously, there's a certain degree of broadness of the confidence intervals, but I think, you know, we're really talking about a pretty comfortable ballpark in terms of the burden estimates.
[Dr. Cody Meissner]
Okay, and let me just, I mean, and make a comment about the reference to influenza. I think early on, many people, including myself, made comparisons with influenza, but I think we've come to find that that's probably not, that the orthomixoviruses behave quite differently than this coronavirus. And that's why you mentioned shift versus drift.

[2:11:01]
I think many people have suggested not continuing with that comparison with influenza because it's a very different virus. So, I have a bunch more questions, but I don't want to hold up.

Response on Comparison with Influenza and Viral Evolution Terminology

[Ben Spader]
Yeah, I mean, so I would say, I think when we compared rates, I think your point is well taken. The goal is not to imply that the pathophysiology of influenza is the same as COVID-19. It's more a sense of the population burden, but I certainly appreciate that distinction. I think similarly, it's maybe a fair comment to think about whether differing terminology from drift and shift should be used for COVID-19. I think the point being is that we've seen at occasions kind of these large punctuated changes in the circulating COVID-19 virus that allows it to evade preexisting immunity.

[2:12:04]
So, you know, I think that's the underlying point, but, you know, it may be worth, I'm looking at my influenza colleague here, worth thinking about whether different terminology should be used for large, rapid changes in the dominant COVID-19 variant that circulates.
[Dr. Martin Kulldorff]
So, thank you for that very interesting discussion, and I think we have a question from Dr. Levi.

Question from Dr. Levi on Viral Evolution and Selective Pressure

[Dr. Rezif Levy]
Yeah, thank you. I have multiple questions, but I'm going to focus on two. One, the first one is building on what Dr. Kohlbrouff asked about the method. So, I'm just looking at the previous slides. Am I understanding correctly that if I look on the over 65, and I look on the percentage of people hospitalized for COVID, about 65 percent of them did not, were not updated on their COVID dose.

[2:13:11]
But at the same time, when I look on the vaccination rates of that particular same age, it does actually look that the vaccinated, the people with updated vaccination are over representative, over represented in the hospitalization. And to some extent, if I look on the methods that is being used to analyze the vaccine efficacy, if the vaccinated are over represented in the COVID arm, but also slightly less over represented in the other arm, we might conclude that the vaccine is effective based on this method, because it's just a relative comparison. But would that be, would that be really the real conclusion? So, I guess my question is, did we kind of scrutinize what are alternative explanations to the analysis that was conducted about the efficacy that might not point to an efficacy of the vaccine, but maybe to a different direction?
[Ben Spader]

[2:14:23]
If I think I'm following your question, it's probably a question about how much we've been able to control for certain confounding variables.
[Dr. Rezif Levy]
So, let me be more precise. So, the method that you're currently using is comparing the relative fraction of people that are updated with their vaccinations between people that came and were tested positive versus people that came and tested negative. And a possible scenario to conclude that the vaccine is effective if they are over represented in both scenarios, but just slightly less on the one in which they tested negative.

[2:15:06]
In that case, you will assume that they are, that the vaccine is protective, but the only thing, but an alternative explanation would be that the vaccine is actually making you more vulnerable for multiple viruses, including COVID, but maybe more so on other viruses than COVID. And the perception is that it's effective. And there are other scenarios. I think that there are other scenarios that you can take the same results that are presented and potentially think about alternative explanations that do not point out to vaccine efficacy, but maybe to vaccine lack of efficacy or deficiency.
[Dr. Martin Kulldorff]
No, that's still one of the weaknesses with the test negative design.

Clarification on Test Negative Design and Alternative Explanations

Yeah.
[Dr. Rezif Levy]
So, I just wanted to make it more precise because some of the data here suggests that maybe actually that's actually happening because the rate of, it seems that the rate of people that are hospitalized with updated vaccination is actually higher than their relative proportion in the population.

[2:16:09]
And that's kind of should make you at least concerned about these options.
[Ben Spader]
Let me link over to, I think Dr. Link-Gelles, who's our SME on methodology.
[Dr. Link-Gelles]
Hi, yes, thank you. So, the goal of a test negative design is to use the controls to represent the vaccination coverage in the population that gave rise to the cases. So, one of the benefits of the test negative design is that these are individuals who have the same symptoms as the cases and sought testing and medical care at the same facilities as the cases. And so, in that sense, these are population-based controls, even though it is a test negative case control design.

[2:17:03]
And then I would add that the representation of the controls of this case, these are not the general population in that they are elderly people who are hospitalized with acute respiratory illness. And therefore, we would not expect them to have the same vaccination coverage as in the unhospitalized, likely healthier general UF population. They're really meant to be representative as much as possible of people who, if they had COVID, would have sought medical care or been hospitalized at the same location. And so, for that reason, we think that the controls here are exactly what we want to understand the relative impact of the vaccination.
[Dr. Martin Kulldorff]
I think we have a question from Dr. Bethe.
[Dr. Tracy Beth Hoag]
Yes, hi.

Question from Dr. Tracy Beth Hoag on Excluding Influenza/RSV Positive Controls

[2:18:00]
I'm sorry to ask a question as the FDA ex officio, but I'm very excited to be able to talk with the first author of this study of looking at the test negative design. And I share Dr. Kulldorff and Dr. Levy's concerns about the potential for confounding. And I'm wondering, you know, if the goal is to really have comparable groups with comparable symptoms, you know, one that happens to test positive for COVID and one that doesn't, why exclude the patients that test positive for influenza and then those over 60 that test positive for RSV? And, you know, are we not concerned that these may be fundamentally different groups of people that are, you know, seeking medical care but happen to test positive for COVID-19 versus something else? And it's really difficult to say their symptoms are exactly comparable. And so, you know, just to get my point in, I think I share a lot of people on this panel's desire to see randomized control trials to minimize these types of bias so we aren't sitting here saying, you know, wondering, you know, are we being misled by these data?

[2:19:15]
So, thanks for your response to that.
[Dr. Link-Gelles]
Yeah, thank you for that.

Response on Excluding Controls and Balancing Case/Control Populations

So, I would add to my previous answer that I think if you include controls or cases that test positive for another vaccine preventable disease, you are actually going to add bias to your study. And there's been quite a lot of published literature by Dahl, et al., and others showing that this would happen. And so, for that reason, we drop controls that tested positive for flu or RSV because the vaccine status is actually correlated. And so, if you had a positive control for influenza, they would be less likely to be influenza vaccinated, also would mean they'd be less likely to be COVID vaccinated because we know that COVID and flu vaccine status are highly correlated.

[2:20:09]
We also do quite a lot of work with the study sites to make sure that the cases and controls have similar symptoms. And we have looked at a number of cases and published looking at number of symptoms among cases and controls, severity of symptoms among cases and controls to ensure that our case and control populations are balanced in that respect. As far as the question about clinical trials, I would actually defer that back to you all at FDA.
[Dr. Tracy Beth Hoag]
Yeah, we're working on that. Thanks. Yeah, thanks for the response.
[Ben Spader]
And I would actually maybe weigh in on one other aspect of this with clinical trials, just realizing some of the real-world realities of the time and cost it takes to do clinical trials.

Comment on Clinical Trials vs. Test Negative Design

And I think the test-negative design has provided a robust way to, in a very timely manner, get real-world data.

[2:21:02]
I mean, to realistically say that, you know, this is June and we're looking at VE data from this last season as the timing would not be possible from a temporal or a cost standpoint to be able to, for CDC to be able to do randomized clinical trials with that. So, I think this is, for us, it's sort of a robust way to be able to rapidly get real-world data very efficiently. Dr. Levi?

Follow-up Question on Viral Evolution and Vaccination Policy Connection

[Dr. Rezif Levy]
Yeah, I guess my second question is maybe on a completely different topic. So, I was looking on the evolution, the genome evolution of the variants. And there are two striking jumps. You see continuous kind of evolution and then two major jumps. And I have two questions related to that. One of them is, did we do any analysis to compare that to other viruses like influenza, for which we have similar data, to see if that's kind of a common pattern?

[2:22:05]
Or these jumps, how common these jumps are at once, almost at once? And if they are not common, what could be some evolutionary pressures? Because usually these jumps come from some pressure, evolutionary pressure. So, to what extent that was analyzed? And maybe also to see if there is, are there any connections to the vaccination policy that we have in that evolution of, in the evolution of the variants? That seems at least kind of striking in terms of its shape, its pattern, so.
[Dr. Martin Kulldorff]
I think we have one more comment from Dr. Meissner, and then maybe I think we should move on.
[Ben Spader]
Do you want me to quickly comment on the evolutionary aspect?

Response on Viral Evolution and Selective Pressure

Yeah, I mean, this has been, I think it's, I mean, has been a, we, it's a field we've been continuing to learn.

[2:23:02]
COVID-19 has thrown us many surprises. Omicron, I think, is a classic example of that, where it was a massive change. It came out of nowhere and caused an incredible infection. I think we've also seen these other punctuated changes. There are likely aspects of selective pressure within the human population due to, say, pre-existing immunity. You know, I think there are also unusual aspects of the virus. So, I think it's a, it's a complex dynamic. There's obviously been a ton of work in the space of monitoring variants, being able to provide sequencing data real time. So, you know, I think it's crucial that we continue to have the capacity to be able to monitor for if and when these surprises occur.
[Dr. Martin Kulldorff]

[2:24:00]
Thank you, and Dr. Meissner?
[Dr. Cody Meissner]
Thank you very much.

Comment from Dr. Cody Meissner on Convergent Evolution and Case Control Design

I just want to add to the complexity of what was just being said, because we're now seeing convergent evolution. That is, various strains are developing the same mutations in certain areas. So, of the spike protein. So, this is a really tough issue to sort out. One, but one, the one point I wanted to say in regard to, in regard to the case control design, it isn't perfect, and I think that's what we're hearing, but it's the best we can do in a limited time period. For example, that's what we are used to assess influenza vaccines, which change every year.

[2:25:04]
So, I mean, a case control, as Dr. Link-Ellis pointed out, I mean, that it, sure, it has biases in favor of the, of a person who's more likely to seek medical attention. So, there are problems, but it is a pretty well established design for looking at vaccines. Over.

Distinction Between Traditional Case Control and Test Negative Design

[Dr. Martin Kulldorff]
Thank you, and I think we have to distinguish between a traditional case control study versus test negative design, because methodologically, I think those are very different in terms of the quality of the information. But we will now have to go move on with Dr. Sarah Meyer from CDC, who will talk about COVID-19 vaccine safety issues.

COVID-19 Vaccine Safety Presentation

Thank you.
[Dr. Sarah Meyer]

[2:26:01]
Good afternoon. My name is Sarah Meyer. I'm a pediatrician and the director of the Immunization Safety Office. Today, I'll be sharing an update on CDC's COVID-19 vaccine safety monitoring. The goal of this presentation is to share with the committee how CDC monitors COVID-19 vaccine safety and what we have found through four and a half years of monitoring these vaccines.

Bottom Line on COVID-19 Vaccine Safety Monitoring

Before I get into the details, I want to state the bottom line up front. CDC and interagency partners launched an extensive vaccine safety monitoring program for COVID-19 vaccines. Many potential safety outcomes were rigorously assessed through complementary passive and active systems. Myocarditis has been causally associated with mRNA COVID-19 vaccines. In addition, adverse events common to all vaccines, such as local and systemic reactions and allergic reactions, have been observed. CDC continues to monitor the safety of COVID-19 vaccines.

[2:27:01]
I apologize. Let me get the slide to move.

Vaccine Safety Monitoring Lifecycle

Vaccine safety monitoring is a key component of the entire vaccine lifecycle. From the preclinical research and development to clinical trials and the reviews by regulatory agencies and advisory groups, safety is evaluated at every step. After a vaccine has been authorized or approved, CDC safety monitoring begins alongside our interagency partners, FDA, Indian Health Service, Department of Defense, and Department of Veterans Affairs.

Complementary Safety Systems

CDC uses strong complementary systems in a layered approach to rapidly detect and assess potential safety concerns in order for public health officials and policy makers to take appropriate action.

[2:28:00]
Most of these systems have been in place for decades, but we are continuing to improve the existing systems as well as identify new systems that are needed to fill gaps, such as v-safe, which was launched to monitor COVID-19 vaccines. Next, I will briefly describe each of these systems in more detail. I'll start with the Vaccine Adverse Event Reporting System, or VAERS.

Vaccine Adverse Event Reporting System (VAERS)

VAERS serves as our nation's early warning system for vaccine safety. This system is co-managed with FDA and involves nationwide spontaneous reporting to rapidly detect safety signals, including rare events. Healthcare providers and manufacturers are required under the National Childhood Vaccine Injury Act to submit VAERS reports for certain types of adverse events in vaccines. However, reports are encouraged from anyone, such as patients or their family member. An important point to stress is that a report to VAERS does not mean that a vaccine caused an adverse event.

[2:29:03]
VAERS is used for signal detection and hypothesis generation and, in most situations, is not able to assess for causality. The Vaccine Safety Data Link, or VSD, is a collaborative model for generating high-quality vaccine safety data.

Vaccine Safety Data Link (VSD)

Thirteen integrated healthcare organizations participate in this network, covering around 15.5 million people per year. VSD involves active surveillance using electronic medical records and chart reviews. This allows for rapid monitoring for pre-specified events of interest, as well as for monitoring for unexpected events. As opposed to VAERS, which is used for signal detection, VSD can both detect as well as assess safety signals. Another hallmark of the VSD is the strong expertise in this network, which has allowed for the development of innovative methods for monitoring safety.

Clinical Immunization Safety Assessment (CISA) Project

[2:30:03]
The Clinical Immunization Safety Assessment, or CISA, project is a network to guide vaccine safety from the individual to the population level. The CISA project includes eight medical research centers with vaccine safety experts and subspecialists. CISA consultants provide individual clinical consultations on complex immunization issues to help guide patient care. CISA investigators also conduct clinical research on vaccine safety, geared towards real-world issues not assessed in pre-licensure trials. Finally, CISA consultants help to inform CDC public health guidance on clinical immunization safety issues.

v-safe After Vaccination Health Checker

Lastly, the v-safe after vaccination health checker is CDC's newest tool and involves direct-to-consumer vaccine safety monitoring. v-safe is a smartphone and computer-based self-reported active monitoring system established during the COVID-19 pandemic.

[2:31:01]
It can serve as the earliest source of information on reactogenicity and other health events for new vaccines and in populations excluded from clinical trials. For example, v-safe provided a conduit to enroll more than 23,000 pregnant women into a voluntary registry to monitor maternal and neonatal outcomes after COVID-19 vaccination. Because it is flexible and able to be rapidly deployed, v-safe is an important tool for emergency preparedness and response. In addition, v-safe is integrated with VAERS to help streamline reporting of serious adverse events. These systems serve as the foundation for CDC's comprehensive approach to studying COVID-19 vaccine safety.

Comprehensive Approach to Studying Safety

This approach includes surveillance to analyze spontaneously reported events, epidemiologic studies to assess specific safety questions, clinical research to help guide clinical practice, a pregnancy registry for a longitudinal assessment

[2:32:04]
of maternal and infant outcomes after COVID-19 vaccination, rapid cycle analyses to quickly detect potential concerns that require further investigation, data mining to assess for over 60,000 potential outcomes in order to detect unexpected events after vaccination, and patient surveys to assess symptoms and health impacts following vaccination. The summary of evidence I'll be presenting in subsequent slides represents a vast body of evidence.

Summary of Evidence

Since COVID-19 vaccines were rolled out in December 2025, safety of COVID-19 vaccines is documented in 17 vaccine safety technical workgroup reports, 28 presentations to federal advisory committees, 29 publications in the MMWR, 114 published manuscripts, and nearly 10 million people enrolled in our newest vaccine safety monitoring system, v-safe.

[2:33:02]
This extensive collection of vaccine safety data occurred during the largest vaccination effort in U.S. history, with approximately 1 billion vaccine doses distributed.

Extensive Vaccination Effort

To quickly recap, there were three types of COVID-19 vaccines that were authorized or approved in the United States, mRNA vaccines by Pfizer, BioNTech, and Moderna, a protein-based vaccine by Novavax, and a viral vector-based vaccine by Janssen.

Types of COVID-19 Vaccines and Janssen Experience

However, Janssen use was limited in the United States. By April 2021, VAERS detected six reports of thrombosis with thrombocytopenia syndrome, or TTS. FDA and CDC issued a 10-day pause in use of the vaccine. By December of that year, ACIP issued a preferential recommendation for mRNA vaccines over the use of Janssen. By June 2023, the EUA for Janssen was revoked, and the vaccine is no longer in use in the United States.

[2:34:06]
The Janssen experience highlights an example of federal safety systems working together to rapidly identify and mitigate a vaccine safety issue. I won't be discussing safety of Janssen COVID-19 vaccine any further in this presentation. For Novavax, there are currently limited post-authorization safety data available in the U.S. This product was authorized later than the mRNA vaccines in July 2022, and there has been limited uptake in the United States.

Novavax Safety Data

Therefore, I won't be discussing Novavax during this presentation either. Thus, I will focus the remainder of this talk on the safety of mRNA COVID-19 vaccines, for which a large body of evidence has accrued over the past few years.

Focus on mRNA COVID-19 Vaccine Safety

Here, I'll describe what we have learned from monitoring the safety of COVID-19 vaccines at CDC.

Evaluation of Specific Outcomes

[2:35:07]
CDC has evaluated at least 65 specific outcomes to assess COVID-19 vaccine safety using a variety of systems and epidemiologic methods.

Weekly Sequential Monitoring in VSD (Rapid Cycle Analyses)

We have conducted weekly sequential monitoring through rapid cycle analyses, or RCAs, in the VSD since the start of the vaccine rollout in December 2020 of up to 23 pre-specified outcomes among over 12 million people. These outcomes were selected based on clinical trial data, known safety findings with other vaccines, or biological plausibility. Sequential statistical testing using automated ICD-10 codes is used to compare incidence of an outcome in vaccinated people during a post-vaccination risk interval versus vaccinated people in a comparison interval. If a potential statistical signal is detected, additional analyses and or chart reviews are conducted.

[2:36:04]
The system is designed to be sensitive. Not all detected signals represent a true safety concern. From 2020 to 2025, eight statistical signals have been detected through VSD's weekly rapid cycle analyses.

Statistical Signals Detected in VSD

These include acute myocardial infarction, venous thromboembolism, immune thrombocytopenic purpura, ischemic stroke, seizure, Guillain-Barre syndrome, Bell's palsy, and myocarditis. After a signal is detected, CDC undertakes further investigations to determine whether a true safety concern is present or whether the statistical signal represents a positive.

Further Investigations of Signals

These include chart reviews, a trend analysis of the reported rate ratios, cluster analyses, additional studies, such as self-controlled case series, and querying other monitoring systems, such as VAERS or databases managed by interagency partners, including the FDA and VA.

[2:37:10]
After completing these investigations, CDC assessed that there is an increased risk for myocarditis following mRNA COVID-19 vaccines.

Increased Risk for Myocarditis

There has been no clear or consistent evidence of a safety concern for the other outcomes I mentioned. Using data from the vaccine safety data link, this figure shows the incidence of myocarditis per million doses administered within seven days of vaccination among 12- to 39-year-olds by season and dose.

Incidence of Myocarditis in VSD

In general, rates of myocarditis peak in 16- to 17-year-olds and are higher in males. Myocarditis is rare in children aged less than 12 years or in adults greater than 50 years of age. As you can see, the risk was highest after the second dose in the primary series, but remained elevated after the first monovalent booster.

[2:38:04]
In subsequent seasons, the incidence has been lower and is more similar to the background rate of less than two cases per million population. We have seen similar patterns with VAERS reports as well. There are a few possible reasons for these lower myocarditis rates in recent years.

Possible Reasons for Lower Myocarditis Rates

At this stage, adolescents and adults have been eligible for multiple vaccine doses. In addition, the longer interdose interval, where most people are getting a dose only once per year at most, is another potential factor. There may be others like higher levels of overall population immunity. FDA has also recently shared updated data on myocarditis and pericarditis following mRNA COVID-19 vaccination from the Biologics Effectiveness and Safety System, or BEST, from the 2023-2024 season.

FDA Updated Data on Myocarditis

FDA issued safety labeling change notification letters to the manufacturers in April to include new safety information on myocarditis and pericarditis.

[2:39:08]
And today, FDA approved safety labeling changes for Comirnaty and Spikevax to include this new safety information.

Follow-up Studies on Myocarditis Recovery

CDC has conducted follow-up studies that show most adolescents and young adults have recovered from myocarditis. These studies are based on surveys of individuals aged 12 to 29 years with myocarditis after mRNA COVID-19 vaccine, for whom a VAERS report was filed during January to November 2021, and their healthcare providers. Based on cardiologists or other healthcare provider assessment, 83 percent of patients were considered fully or probably recovered by 90 days after onset of myocarditis. And by one year, at least 90 percent were considered fully or probably recovered.

[2:40:02]
Most people experienced improvement in their symptoms and cardiac imaging and testing results. However, there was a subset of patients who underwent a cardiac MRI at least one year after onset. The most common abnormality seen was late gadolinium enhancement, which could indicate fibrosis. The clinical significance of this finding is unclear, especially as most of these patients were considered recovered by their provider and had been cleared for all activity. There were no known deaths or cardiac transplants among this group. Next, I'll review COVID-19 vaccine safety in children ages 6 months to 11 years.

COVID-19 Vaccine Safety in Children 6 Months to 11 Years

The risk of myocarditis following COVID-19 vaccines in children aged less than 12 years is low, particularly for those aged 6 months to 5 years. Active sequential analyses in the vaccine safety data link have demonstrated no statistical signals for myocarditis in children.

[2:41:03]
Furthermore, there have been no confirmed cases of myocarditis in children less than 5 years of age in either VAERS or the VSD. In addition, rapid cycle analyses in the VSD demonstrate no increased risk for 22 other pre-specified outcomes following COVID-19 vaccination. Finally, evaluations to assess multisystem inflammatory syndrome in children, or MISC, following COVID-19 vaccination have demonstrated that most patients had evidence of preceding SARS-CoV-2 infection. One issue I wanted to note is that the majority of COVID-19 vaccine reports submitted to VAERS in children aged less than 12 years of age are related to vaccine administration errors.

MISC Following Vaccination

Approximately 74% of reports in children aged 6 months to 4 years and 70% of reports in children aged 5 to 11 years were related to vaccine administration errors from October 2021, when vaccines were first authorized in this age group, to April 2025.

Vaccine Administration Errors in VAERS

[2:42:07]
Few of these reports included an actual adverse event. They were reporting, they were simply reporting an error in administration, with most of them related to expired product administered, incorrect dose administered, incorrect product formulation administered, product administered to patients of an inappropriate age, and product preparation error or issue. The high proportion of VAERS reports related to vaccine administration errors in this age group is likely related to the complexity of the pediatric COVID-19 vaccination program, especially earlier in the rollout, with different products requiring different dosing regimens, changing recommendations, and complicated storage and handling requirements.

Preventing Vaccine Administration Errors

CDC is expanding its work to prevent vaccine administration errors in collaboration with FDA. Some of CDC's available resources for healthcare providers are shown on this slide.

Safety of COVID-19 Vaccines in Pregnant Women

[2:43:08]
Next, I'll discuss CDC's activities to assess the safety of COVID-19 vaccines in pregnant women. CDC launched a voluntary COVID-19 vaccine pregnancy registry, which enrolled over 23,000 pregnant women. We have conducted seven observational studies based on survey and medical record information. We have also evaluated the safety of COVID-19 vaccines in over 45,000 pregnant women in the VSD, with 11 cohort case control and surveillance evaluations to date.

No Increased Risk for Maternal or Pregnancy Outcomes

Across these CDC studies, the evidence shows no increased risk between COVID-19 vaccines and maternal outcomes, including 25 medically attended adverse events, serious acute adverse events, pregnancy-related conditions, and maternal ICU admission. In addition, maternal vaccination was not associated with pregnancy outcomes, including miscarriage, stillbirth, preterm birth, and small for gestational age.

[2:44:09]
Maternal COVID-19 vaccination was also not associated with major birth defects, neonatal ICU admission, or infant deaths.

Studies Addressing Public Concerns (Uterine Bleeding, Tinnitus)

CDC has also conducted studies to address vaccine safety concerns from the public. For example, based on reports of abnormal uterine bleeding after receipt of a COVID-19 vaccine, CDC conducted studies in VAERS, VSD, and V-safe. VSD studies demonstrated that the availability of COVID-19 vaccines was not associated with a change in incidence of medically attended abnormal uterine or postmenopausal bleeding. In addition, the receipt of COVID-19 vaccine was not associated with greater bleeding severity. CDC also assessed whether COVID-19 vaccines were associated with the development of tinnitus by conducting data mining through VAERS and VSD.

[2:45:02]
Based on the lack of signals detected in either system for tinnitus, the findings from CDC studies did not support an increased risk of tinnitus after COVID-19 vaccine.

Safety Monitoring of Death Reports in VAERS

Next, I'll describe CDC's activities for safety monitoring of death reports following mRNA COVID-19 vaccination, first starting with our analysis in VAERS. As of May 30th, 2025, there have been 19,417 domestic deaths reported to VAERS after COVID-19 vaccination. Before I delve further into the data, there are a few important considerations related to evaluation of death reports in VAERS. First, the FDA emergency use authorizations and CDC COVID-19 vaccination program provider agreements required healthcare providers to report all deaths following COVID-19 vaccination to VAERS, regardless of cause or circumstances surrounding the death.

[2:46:02]
Of note, this requirement does not apply to other vaccines. In addition, VAERS generally cannot assess causality of adverse event reports, including deaths.

Considerations for Evaluating Death Reports in VAERS

We conducted an evaluation of deaths following mRNA COVID-19 vaccination in VAERS through January 31st, 2023, which I will describe in the next set of slides. During this time period, there were 17,631 domestic VAERS reports of death following COVID-19 vaccine.

Evaluation of Deaths in VAERS (Through Jan 2023)

CDC takes every report to VAERS seriously, especially deaths. CDC requests medical records, death certificates, and autopsy reports for every death reported to VAERS. After review by a CDC clinician, 52 of these reports were determined not to be a death and were excluded from the analysis. An additional 1,790 reports were excluded because the vaccine type received was something other than an mRNA vaccine, which was the focus of this analysis.

[2:47:09]
2,940 reports were excluded because we had no information on the cause of death, despite exhaustive efforts to obtain this information. This leaves us with 12,849 reports with a cause of death available through autopsy, death certificate, medical record, and in a minority of reports through the VAERS report alone. The cause of death was classified based on ICD-10 categories.

Cause of Death Classification

Among these reports, approximately 78% were aged 65 years and older, 15% were 50 to 64 years of age, 6% were 18 to 49 years of age, and 0.5% were aged less than 18 years of age.

Age Distribution of Deaths

[2:48:00]
Next, we assessed all deaths reported in the general U.S. population during this time period. These data are based on death certificates for U.S. residents, which are maintained in the National Center for Health Statistics multiple cause of death database.

Deaths in the General U.S. Population

These data on cause of death are categorized by ICD-10 diagnostic codes. We then conducted observed to expected ratio analyses for each age group by comparing the number of observed cause-specific deaths among vaccinated persons reported to VAERS to the number of expected deaths in the U.S. population within 42 days of vaccination with an mRNA COVID-19 vaccine.

Observed to Expected Ratio Analyses

We found that the reported rates of death after mRNA COVID-19 vaccination were below background rates of death in the general U.S. population.

Most Common Causes of Death in VAERS Reports

The most common cause of death reported to VAERS are generally consistent with leading causes of death in the U.S. population. If you look by age group, you can see that for all ages, the leading causes of death among VAERS reports were diseases of the heart, COVID-19 disease, cerebrovascular diseases, and general signs and symptoms, which primarily included people whose cause of death was listed as shock.

Observed to Expected Ratio Below One

[2:49:16]
For children, congenital malformation was also reported, and for adults 18 years and older, malignant neoplasm was included. Across the board, the observed to expected ratio was below one, which indicates a lower observed death rate than what would have been expected within the post-vaccination period of 42 days. Even when taking into account the limitations of VAERS, these findings suggest no association between COVID-19 vaccination and mortality.

Self-Controlled Case Series Evaluations in VSD (Mortality)

In addition to reviewing reports in VAERS, we conducted two self-controlled case series evaluations in the vaccine safety data link, one in the general population age 12 years and older, and one in Medicare beneficiaries age 65 years and older.

[2:50:04]
We looked at Pfizer and Moderna vaccines separately and found that in both studies, there was no increased risk in the 28 days after vaccination for non-COVID mortality, all-cause mortality, cardiac-related mortality, and non-COVID cardiac-related mortality, as shown by the relative incidence rates that are all significantly below one. These results are consistent with a separate cohort analysis conducted through the VSD as well.

Consistency with Cohort Analysis

The robust methods used for these VSD analyses provide further confidence of no increased risk of mortality after mRNA COVID-19 vaccines. In fact, there appears to be a protective effect of vaccination. I've gone through a snapshot of data that CDC has collected to assess for adverse events after COVID-19 vaccination.

Data Mining for Unexpected Events in VSD

But you may be wondering, how do we know we're not missing something, something we're not even looking for?

[2:51:00]
And the answer to that is CDC uses data mining in the vaccine safety data link to assess for unexpected events after COVID-19 vaccination. This allows us to assess for over 60,000 possible adverse events in the 70 days after vaccination using tree-based data mining of ICD-10 codes. We have done these assessments for the primary series, the initial booster, and the bivalent booster. Through these analyses, we have not identified any new safety concerns outside of known events, including myocarditis and pericarditis, allergic reactions, and common local and systemic reactions. So, to summarize, we have identified several adverse events following mRNA COVID-19 vaccines.

Summary of Identified Adverse Events

Most of these, including local and systemic reactions, acute allergic reactions, syncope, and shoulder injuries can occur with any vaccine. Myocarditis and pericarditis have been observed following COVID-19 vaccination.

[2:52:03]
We arrived at these conclusions by evaluating at least 65 specific safety outcomes, conducted data mining of at least 60,000 potential outcomes for unexpected concerns, investigated numerous statistical signals, and conducted many epidemiologic studies. Our findings are consistent with the National Academies of Sciences, Engineering, and Medicine in their consensus report on adverse effects of COVID-19 vaccines.

Consistency with NASEM Consensus Report

This report was commissioned by HRSA and published in 2024. Over 400 studies on the safety of COVID-19 vaccines were reviewed as part of this evaluation. NASEM concluded that the evidence supported a causal association between mRNA COVID-19 vaccines and myocarditis, and that the evidence favors rejection of a causal relationship between vaccination and six additional outcomes, including Guillain-Barre syndrome, Bell's palsy, TTS, myocardial infarction, ischemic stroke, and female infertility.

[2:53:05]
The evidence was inadequate to accept or reject a causal relationship for 13 other outcomes. In summary, COVID-19 vaccines have been evaluated under the most extensive vaccine safety monitoring program in U.S. history.

Summary of Safety Monitoring Program

Safety surveillance rapidly identified and characterized the risk of myocarditis after mRNA COVID-19 vaccination. We identified no other confirmed safety concerns except those seen with any other vaccine, such as local and systemic reactions or allergic reactions. CDC continues to prioritize the monitoring of COVID-19 vaccine safety with at least 30 ongoing studies or activities.

Continued Safety Monitoring

Next, I'll turn it to Dr. Georgina Peacock to review vaccine coverage and implementation. Thank you. DR. GEORGINA PEACOCK. Thank you so much.
[Dr. Mina Zadeh]
Before we go on, we have a CDC SME on the line, Chris Taylor.

CDC SME Response on Pediatric Hospitalization Rates

Dr. Taylor, if you would please ask your or respond to the questions from the previous session.

[2:54:04]
Thank you.
[Dr. Christopher Taylor]
DR. CHRISTOPHER TAYLOR. Hi, thank you. Yes, I just wanted to circle back. There was a question about the rates among the young children that were presented for COVID that Dr. McNeil presented previously. I just wanted to point out that on the slides, what we show are cumulative rates, which are the sum of weekly rates over a period of time. And as Dr. McNeil presented, over the July 2024 through May 2025 period, rates among young children, children less than six months, their cumulative rate was 268 hospitalizations per 100,000 population. I wanted to clarify because I think if you were to just look at the weekly rates, week by week, those do seem very small, but as we present them cumulatively over a season or a period of months, they are larger.

[2:55:02]
As Dr. McNeil presented, the cumulative rates for infants less than six months of age are comparable to adults 65 to 74 years of age, around 270 per 100,000. And we see a similar pattern for children six to 23 months of age, that cumulative rate over that basically one-year period is 100 per 100,000, comparable to adults 50 to 64 years of age that are 103 per 100,000. Again, those are cumulative rates, which are the sum of cumulative weekly rates for a period of time.
[Dr. Mina Zadeh]
Okay. Thank you. Dr. Levi?
[Dr. Rezif Levy]
Just a quick question.

Question on Comparison with Overall Hospitalizations

If I would take those proportions and I just look on overall hospitalizations from all causes on these age groups, would I get different proportions or similar proportions? In other words, do we see here something that is deviating from the pattern of general rates of hospitalizations among different age groups, or this is just consistent with those patterns?

Response on Comparison with Overall Hospitalizations

[Dr. Christopher Taylor]

[2:56:13]
I guess I would say that COVIDNet, as one of the ResNet platforms, is limited to examining and collecting data on SARS-CoV-2 positive COVID-19 associated hospitalizations. So, we have not done an analysis that compares the general population. However, I will say at previous ACIP meetings, we do have an analysis that examines rates of underlying conditions among adults hospitalized with COVID-19 versus those in the general population. And so, we were able to identify certain underlying conditions that increase an adult's risk for COVID hospitalization. But we have not, we're not in a position with COVIDNet data to compare COVID hospitalization rates to general hospitalization rates.

[2:57:06]
That's not data that we have. Thank you.
[Dr. Mina Zadeh]
Dr. Hiplin?

Question on Risk-Benefit Evaluation

[Dr. Joseph Hiblin]
Captain Myers, thank you for your clear presentation of safety. I've always had an interest in risk-benefit calculations, and I'd like to see if this concords in a broad category. It seems to me that you're presenting very few, if none, if no risks of death for receiving a COVID vaccination. And in broad measure, Dr. McNeil's presentations was that there's a substantial risk of not receiving a vaccination. And the benefit of receiving a vaccination would be at least a 40%, 50% reduction in risk, just in broad terms.

[2:58:06]
So, the risk of an adverse event, for example, death from getting a vaccination is zero. And by broad strokes, the benefit of getting a vaccination is a 40% to 50% reduction of risk. Is this a reasonable, broad scope evaluation of risks and benefits?
[Dr. Sarah Meyer]
Thank you for that question.

Response on Mortality Risk and Benefit Calculation

You know, I think you're correct that we have done several studies now to look for increased risk of mortality after COVID-19 vaccines. And we have not seen that in our data. Through the VAERS assessment, where we looked at what we would have expected, you know, is it above expected? And the answer is no. When we looked at in the VSD, is there any increased risk of mortality after COVID-19 vaccines? We didn't see an increased mortality in COVID-19 vaccines.

[2:59:03]
So, I think from a safety perspective, we feel confident in our data that there's no increased risk of mortality after COVID-19 vaccines. But in terms of, you know, the risk benefit assessment, you know, that, you know, I look forward to hearing, you know, from the committee, their assessment of that risk and benefits. I don't know if my colleague wants to add anything on the benefit side.
[Ben Spader]
Yeah, I mean, I just, you know, I was playing around with the ballpark calculation here. So, let's say we figure there are about 40,000 deaths due to COVID-19 last year. Hypothetically, let's say nobody was vaccinated in that population. Then if you look at the other side, let's say all 40,000 of those hypothetical deaths were vaccinated with the VE, the added benefit of VE, that would mean about half of those, about 20,000 of the 40,000 deaths would not occur. So, that's kind of, you know, I backed the envelope, thought about what added benefits on the death side there.
[Dr. Mina Zadeh]

[3:00:06]
Dr. Malone.

Question on Time Windows for Safety Monitoring

[Dr. Robert Malone]
Thanks. I had a number of questions and very much appreciated your ability to rock through data in a short period of time. But we've moved on from that section. Regarding the safety monitoring, just for clarification, there are two windows of time post-vaccination. Post-vaccination being defined as having completed at least two doses, correct?

Clarification on Time Windows for Death Analyses

[Dr. Sarah Meyer]
Are you referring to a specific analysis like the rapid cycle analysis or are you speaking more generally?
[Dr. Robert Malone]
I'm speaking of the data that you shared here. So, the windows of time that you're presenting data on are either 28-day or 42-day post-vaccination defined as fill in the blank.
[Dr. Sarah Meyer]

[3:01:02]
Okay. For death analyses, yes, that is correct.
[Dr. Robert Malone]
Yes. Okay.

Clarification on Time Windows for AE Association Analysis

So, post-vaccination being one dose, two dose?
[Dr. Sarah Meyer]
We looked at at least one dose. And then for our VSD analyses, we looked at, we did three different analyses. So, we did after the primary series, so completion of a primary series. Then we did after the original booster. And then we did after the Omicron booster.
[Dr. Robert Malone]
And then for the analysis of AE association, that analysis, so you were just referring to deaths, the analysis of AE association was also limited to a time window of 28 days?
[Dr. Sarah Meyer]
We have a number of different ways that we look at.

Response on Different Time Windows and Analytic Methods

So, there's a few different windows that we look at depending on kind of which analytic method we're using. I'd like to invite Eric Weintraub, who's our kind of expert in methodologies, to kind of walk through the different post-vaccination intervals that we use.
[Speaker 31]

[3:02:07]
Yeah. Hi. How are you doing?
[Eric Weintraub]
Good afternoon. This is Eric Weintraub with the Vaccine Safety Data Lab. Yeah.
[Dr. Cody Meissner]
We set up for the primary series to look at 21-day and 42-day risk intervals following dose one and dose two. And it's similar to what we've done then following each new vaccine that's come as a recommendation up to this past season.
[Eric Weintraub]
And what that allows us to do is then also scan within the 42 days to see if there's any other intervals that might be elevated using Martin Koldorf's clustering technique to look for increased risk during certain time periods. So, it's very common for us to look at 42 days and then also look at a comparison time.
[Dr. Matthew Clark]
And our comparison time historically for most of these outcomes are going to be days 43 to 84.
[Dr. Robert Malone]
Roger.

Comment on Transparency of AE Analyses

[3:03:00]
So, in this analysis or these analyses, my understanding, because I frankly, if you'll forgive the coaching, the slide that lists a series of AEs that have been among the 65 assessed is a little hard to, it would be preferable if that was structured in a way that we really knew what all of those 65 analyses were and we could, you know, sort it by alphabetical order or something. So, I infer, having tried to pick through that, that hypertension, tachycardia, and POTS were analyzed and were not correlated.
[Dr. Sarah Meyer]

[3:04:00]
Excuse me. So, we have looked at our data a number of different ways. And I'll try to walk through some of that. When we look through VAERS, for VAERS, we have certain lists of pre-specified outcomes that we want to make sure that we can review and flag so that we can review those in more detail. So, those are part of that list. For VSD, we do the same. We have a list of outcomes that we want to look at. And then we have other things that come up that we want to do a study on. So, that comprehensive list of, you know, specific outcomes that we looked at, that was, we can certainly provide you, you know, more detail. That was meant, in a very short presentation, to give you just a flavor of the things that we have been working on. So, we have looked at those outcomes. But like I mentioned, we also did data mining where we look at, we don't specify what we want to look at. We just say, somebody got a vaccine and we want to look to see, is there anything that pops up that we weren't expecting?

[3:05:03]
And we did not see any of those outcomes pop up in our data mining as well. There have been a few studies done related to those, you know, for example, you mentioned POTS. There's a few studies that have been referenced in the NASEM report I showed you. And there's, you know, but there's very limited data. I mean, there's very limited data on those outcomes. But what I can say is based on our comprehensive approach to looking forwards and backwards and sideways to try to figure out, you know, are there any adverse events that we're missing after COVID-19 vaccination? What I showed you, you know, myocarditis and then common reactions found with all vaccines is what we have found.
[Dr. Robert Malone]
So, if I can, again, gentle coaching, I think in the interest of the public interest and transparency, it would probably behoove all of us to make available some listing clarification of those types of analyses and those outcomes that have been queried.

Question on Lot-to-Lot Variability in Adverse Events

[3:06:13]
And then another follow-up, there is, there are some data suggesting there may have been significant lot-to-lot variability in terms of adverse event profiles. If there was lot-to-lot variability, it might make it very challenging to identify clusters of AEs that might be associated with particular lots if one is looking in aggregate. Is that a topic that has been considered, discussed, analyzed, how have you approached it? You know, so query possibility of lot-to-lot variability, how's that been addressed?

[3:07:01]
Over.
[Dr. Sarah Meyer]
Yeah, thank you for that question.

Response on Lot-to-Lot Variability and FDA Role

So, I think the kind of answer goes back to one of the first slides I gave is that we work with, very closely with our interagency partners. We all work on safety, but we all have somewhat different roles. And, you know, lot issues, those are typically assessed by FDA. So, I would defer to my FDA colleague if there's anything to add there.
[Dr. Martin Kulldorff]
Thank you for your answers.

Clarification of POTS

So, yes, the clarification, POTS stands for Postural Orthostatic Tachycardia Syndrome. We have a question from Dr. Meissner and then Dr. Levi after that. So, please, Dr. Meissner.
[Dr. Cody Meissner]
Thank you very much.

Comment and Question from Dr. Cody Meissner on VAERS and Myocarditis Follow-up

And, first of all, I want to compliment Dr. Meyer on a very clear and thorough presentation. So, I now have a comment and then a question for Dr. Meyer.

[3:08:04]
First of all, as a physician, I just want to remind everyone what VAERS is. Every resident is taught to report any adverse event that occurs after vaccination to the VAERS program. And regardless of whether it might be related to the administration of a vaccine or not, we are taught and educated and instructed to report that. So, recognizing that there are tens of thousands of vaccines administered every day, there are obviously going to be a lot of adverse events that occur that are utterly unrelated to administration of the vaccine. So, VAERS is not designed to determine rates.

[3:09:05]
If there's a signal that's picked up in VAERS, then my understanding is that then people look more specifically, for example, in VSD to see if there is a correlation. But the vast majority of reports that are made to VAERS by either the vaccinee, the parents, the pharmaceutical company, have nothing to do with the vaccine. But we are taught to report that regardless in case there might be something that's unanticipated. So, I think people need to realize that the overwhelming number of reports to VAERS are unrelated to administration of a vaccine. Now, the question that I would like to ask Dr. Meyer, and thank you for the very interesting data. It's the first time I've seen it that the rate of myocarditis was 38 per 1 million.

[3:10:06]
And I think if I remember correctly, you said that the current rate is two cases per million. So, that's probably, I would guess, the background rate of myocarditis in this population, which I think is very reassuring. But the question I have for you relates to the long-term follow-up of myocarditis. As you pointed out, there have been studies that have reported on gadolinium-enhanced MRIs that have indicated scarring in the myocardium. And even though the vaccinee feels fine and is doing well, the concern is that that may predispose to cardiac arrhythmias and death later on in life.

[3:11:14]
So, the question I have is, and I think the vaccine industry was asked to look at troponin levels, markers of vaccine injury to the myocardium after the vaccine, thinking about the issue of subclinical myocarditis. And could there be changes that were subclinical but yet predisposed to arrhythmias later in life? I've never seen that data. I believe the companies were asked to generate that data, but I have not seen it, and I don't know what's happened to it.

[3:12:07]
Over.
[Dr. Sarah Meyer]
Yeah, no, thank you for bringing this up.

Response on Subclinical Myocarditis and Long-Term Monitoring

I think with relation to your question about subclinical infection, there have been some studies with biomarkers, troponins assessed with people who were asymptomatic. I think, you know, what those data show is these people didn't have any adverse clinical outcomes. But, you know, I think the long-term significance is something that will need to be continued to follow. And, you know, this is something that CDC has been monitoring closely. FDA is also continuing to monitor. They have a similar study where they have found similar findings, and I believe that will also be included in the safety labeling change that will be posted soon. And I know with us and with FDA, there are continued plans to monitor this up over the long term.
[Dr. Martin Kulldorff]

[3:13:04]
Thank you for those important points by Dr. Meissner about both theirs and myocarditis, and the very thoughtful response by Dr. Meyer.
[Dr. Rezif Levy]
Now, Dr. Levi?

Question from Dr. Levi on Risk Intervals and Long-Term Effects

Yeah, I just wanted to raise two questions. So, one of the two aspects that are very relevant when you do surveillance for safety are what outcomes you are focusing on and what risk intervals and timeframes. And I think it's fair to say that most of our traditional approaches have some implicit assumption that most of the harm is going to happen just immediately after the vaccine is being taken and is going to be reduced over time. But I wonder to what extent we need to inform or maybe change our approach when it comes to the COVID vaccine, given the quite established evidence that we currently have that, at least in some patients, there is residual mRNA and spike for months, if not years, staying in the body and distributed in different organ systems, potentially randomly across different people.

[3:14:16]
It seems to me that that could challenge the sensitivity of most of our traditional approaches. And maybe we need to adapt somewhat broader set of approaches. For example, one approach could be to compare the impact of different vaccines. So, in that respect, I just want to point out a very, very interesting and good, I would say, study from the VA system that compared Moderna and Pfizer vaccines in quite a matched way and actually did show that at least it does look that the Pfizer vaccine has more adverse events following vaccination.

[3:15:02]
Another example could be when you compare death rates, you have to also think about the healthy vaccine effect. Did we compare death rates after COVID versus death rates after influenza vaccine? So, I'm just asking to what extent we are considering broader set of methods, given the unique attributes of these vaccines?

Response on Safety Systems and Long-Term Outcomes

[Dr. Sarah Meyer]
DR. KATE BROWN-FLEMING Well, I will defer the question related to kind of your, I think your question or comment about spike protein and, you know, the immunology there. But I think with relation to how are we thinking going forward about our safety and is it well adapted to the situation? I think we feel very confident in our safety systems in the U.S. We have one of the best safety systems in the world, but we are continuing to think through ways of how to improve them. And I think one thing you're getting at is our ability to monitor long-term outcomes of vaccination. And obviously, that's very difficult.

[3:16:00]
The longer you get out from vaccination, the more you can introduce confounding effects or other things that are unrelated to the vaccine. And the ability to tease out vaccine versus other effects becomes much more challenging. But I think we would welcome input from the committee on, you know, how to better do that.

Comment from Dr. Robert Malone on Novel Product Profile and Delayed Effects

[Dr. Robert Malone]
DR. GARY GENSLER. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. a good point. I think that's a good point.

[3:17:00]
I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. I think that's a good point. a good point. I think that's a good point. I think that's a good point. I think that's a good point. These products are associated with secondary effects on overall immune function that might impact other infectious diseases. This was one of the basis, one of Dr. Levy's pointed questions about the vaccine effectiveness sampling estimate method. So, I infer that really in the safety analyses, what I observe are, as you point out, a kind of a traditional approach, rigorous traditional approach, a world-leading rigorous traditional approach.

[3:18:13]
but might be improved by considering the clinical context of a very novel product profile that is reasonable to infer that there may be delayed effects because we have this chronic exposure to antigen and also to the active material. And we also have one, there's some evidence that there are effects broadly based on immune function, not just the narrowly focused positive effects that we think of, of neutralizing antibodies or et cetera.

[3:19:06]
So, I would, I think we, I think the public would benefit with expanding your mission, that's a good thing, right, to include some of these immunologic potential risks and benefits as well as the actively incorporating the possible risk of delayed onset effects given that the pharmacokinetics of this product are very unusual compared to even live attenuated vaccines. Does that make sense to you?
[Dr. Sarah Meyer]
Well, what I will say before turning it over to my colleague to talk more specific about the immunologic components of your question, I think, you know, we started vaccination back in December 2020.

Response on Long-Term Monitoring and Immunologic Components

[3:20:12]
And so, we have several years now if, you know, we are continuing to monitor in a very robust way to capture any and all adverse events, even if they're cumulative over years from different doses, if we were seeing any effects on organ systems or, you know, safety concerns of any kind, we would be well equipped to pick those up in our safety systems. But I do want to give Dr. Thornburg a chance from an immunologist perspective on this question.
[Dr. Martin Kulldorff]
If you can keep that short because we are short on time right now.

SME Response on Protein and mRNA Detection Studies

[Dr. Sandra Fryhofer]
Yes, thanks. So, there has been some data looked at both in preclinical studies, which are animals, and then some limited studies about protein detection and mRNA detection in human.

[3:21:10]
Most of the preclinical studies in animals are cases that protein detection is detected up to 90 in the injection site, but not in liver. And beyond that, there's no protein detected. In humans, there have been some studies. Notably, there's one that's been conducted in autopsies in 20 individuals. And in those 20 individuals, there was none of the patients had vaccine detected in the liver spleen or medicinal lymph nodes, just the oxygenated lymph nodes after 30 days. As far as protein detection goes in those patients, they did not detect any protein in lymph node, left ventricle, right ventricle, liver, only nonspecific staining.
[Dr. Martin Kulldorff]

[3:22:11]
Thank you.

Acknowledgment of Scientific Discussions

Scientific discussions are fascinating and wonderful to have, very important in this case. We now have to move on because we're behind time. So, I'm going to ask Dr. Georgina Peacock to talk about COVID vaccine and CARB version implementation.

COVID Vaccine Coverage and Implementation Presentation

[Dr. Georgina Peacock]
All right. Thank you. Good afternoon. I'm Dr. Georgina Peacock. I'm a pediatrician and the director of the Immunization Services Division, and I'll be presenting on COVID-19 vaccination implementation.

Data Sources for Vaccination Coverage

Before I discuss COVID-19 vaccination coverage, I thought it would be helpful to explain the source of data that I will present. One of the data sources that the Immunization Services Division uses to obtain data on vaccine coverage like COVID-19 vaccination and other information on immunization implementation is the National Immunization Survey or NIS.

[3:23:14]
The NIS is a random digit dial cellular telephone survey of adults 18 years and older in the United States, local jurisdictions and associated territories. Data for children are reported by their parent or guardian. All responses are self-reported and the sample size is approximately 15,000 adults weekly or about 60,000 adults monthly. The data is weighted to represent a non-institutionalized U.S. population.

COVID-19 Vaccination Coverage Among Adults

And so now to COVID-19 vaccination coverage. This slide shows the 2024-2025 COVID-19 vaccination coverage for at least one dose among adults 18 years and older in the bottom dark blue line and among adults 65 years and older in the top light blue line from September 2024 through April 2025.

[3:24:12]
Vaccination coverage among older adults reached 44% for one or more doses and 23% for all adults greater than 18 years.

Coverage Increase for Older Adults

COVID vaccination coverage increased for older adults between the 2023-2024 season and the 2024-2025 season. For those 65 to 74 years of age, vaccination coverage rose almost 5 percentage points in the most recent season while for adults 75 years and older coverage improved by about 8 percentage points by the end of the 2024-2025 season. This slide shows COVID-19 vaccination coverage estimates for the pediatric population.

COVID-19 Vaccination Coverage Among Pediatric Population

[3:25:02]
Approximately 5.6% of children less than 4 years of age were up to date with COVID vaccination according to current recommendations for that age group shown in light blue. In children 5 years and older, up to date is defined as receipt of at least one vaccination since August. For children between 5 and 17 years of age, almost 16% have received at least one dose. Overall, approximately 13% of children between 6 months and 17 years of age were up to date with their COVID vaccinations at the end of April 2025.

Coverage Among Immunocompromised Adults

For immunocompromised adults 18 years and older who received their first COVID vaccine dose in August or September of 2024, 8% were fully vaccinated with two doses by the end of the season. When coverage is stratified by age, 16.6% of those in the 50 to 64 year age category were fully vaccinated compared to 2.4% in the 18 to 49 year category and only 0.8% in the 65 year and older category.

Summary of Coverage Data

[3:26:16]
In summary, COVID-19 vaccination coverage for older adults improved in the 2024-2025 season compared with the previous season. Vaccination coverage for all adults greater than 18 years was similar between seasons and approximately 13% of children between 6 months and 17 years of age were up to date with COVID vaccination at the end of April 2025. Thank you.
[Dr. Rezif Levy]
Do we have data about the vaccination rates among medical professionals?

Question on Vaccination Rates Among Medical Professionals

[3:27:01]
I think, I guess the motivation to ask this question is that, you know, these are the people that are supposed to advise patients about vaccination and I think their acceptance of the rationale of vaccination is probably important to get some signal about how it's being accepted in the public and specifically in this population.

Response on Healthcare Provider Coverage Data

[Dr. Georgina Peacock]
I think you were asking, I didn't quite hear about healthcare professionals, is that right?
[Dr. Rezif Levy]
Medical, yeah.
[Dr. Georgina Peacock]
Yes, okay. Not in this specific data set in the National Immunization Survey. We do look at that data through some other data sources and I could bring that to another ACIP meeting or to the work group or, and I can check with our SMEs that are on the line, but I don't think we have that right now.

Question from Dr. Cody Meissner on Low Uptake and Recommendation Influence

[Dr. Martin Kulldorff]
Dr. Meissner.
[Dr. Cody Meissner]
Yeah. Thank you, Dr. Peacock.

[3:28:00]
And I have a question that's probably difficult to answer, but one that I've thought about recently. So the uptake of the vaccine is pretty low. It's less than 20% among young children and even among the highest risks, people over 75, it's, it's, it's disappointingly low. But my question for you is, at what point does the reception of a vaccine or the willingness to administer, to have a vaccine administered influence the recommendations that are issued by the ACIP? I mean, is that a consideration? If, if, if no, if children simply are getting at a rate of less than one out of five, does that impact the recommendation that, that you make?

[3:29:01]
Over.

Response on Uptake and Committee Discussion

[Dr. Georgina Peacock]
Well, I think that's the, the discussion for the, for the committee, so I'll turn that back. I, I do think what we were encouraged to see this season was the increase in vaccination for those over 65 and particularly those over 75. And I, I do think that that reflect, may reflect a few things. It reflects that healthcare providers may be providing a recommendation to those that they're seeing that have risk factors for hospitalization or increased risks for hospitalization and death. It also may, well, I'll just stop there. And, and, and obviously the, the recommendation that comes out of ACIP is that of the committee.

Comment on Public Confidence and Recommendations

[Dr. Cody Meissner]
Yeah, thank you for that. I, my only concern is that if the CDC makes a recommendation that people simply are not going to follow, that's, I mean, it's troubling because people lose confidence in a recommendation then.

[3:30:05]
So I just, and I know there's no easy answer to this, but I, I think it does need to be considered at some point. Over.
[Dr. Martin Kulldorff]
I think as, as the committee, we have to make recommendations that is evidence-based.

Response on Evidence-Based Recommendations and Trust

We have to use the evidence-based medicine. But I think, I mean, there has been a recommendation in place, vaccinating children. And the fact that it's so low is a reflection of the, the lack of trust that many parents have with the COVID, COVID vaccine recommendations that the ACIP has been given. So it's a very important question that you're asking, Dr. Meissner. Thank you. Thank you.

Question from Dr. Vicki Pepsworth on Low Uptake and VAERS Reports

Dr. Perez will have a question.
[Dimitri Daskalakis]
I just wanted to make one comment. This is Dimitri Daskalakis from NCIRD.

[3:31:02]
Just to add to something that Dr. Peacock said is that part of our evidence to recommendations framework that is taken into the workgroup does include an assessment of feasibility and acceptability. And so I think that is, that has historically been a piece of what's been a part of all discussions around vaccinations. Just wanted to clarify that, that is a piece of what is built in to the discussion that ultimately leads to discussions here and then ultimately recommendations. Thank you.
[Dr. Cody Meissner]
Thank you for that comment.

Comment from Dimitri Daskalakis on Feasibility and Acceptability in ETR

Follow-up Question on Threshold for Making Recommendations

But can I just ask, is there a threshold? At which you decide making a recommendation is probably not beneficial?
[Dimitri Daskalakis]
I think that that is actually the exact reason for the discussion in the committee.

Response on Committee Discussion and Review Process

So I think that as that is reviewed in the workgroup, that is brought in front of the committee with the feedback from the workgroups, then ultimately the committee makes recommendations that can then be reviewed. Thank you.
[Dr. Martin Kulldorff]

[3:32:02]
Thank you.

Last Question from Dr. Vicki Pepsworth on Animal Studies and Biodistribution

And I think we have a last question from Dr. Petchworth.
[Dr. Vicki Pepsworth]
Yes. Thank you very much for this very enlightening presentation. I am very concerned because with uptake being as low as it is reported and also the reports to VAERS are extremely high compared to other vaccines.

Comment on VAERS Underreporting

They are, the last time I looked, it was about 1.6 million reports that came in. I don't know the extent to which underreporting is still an issue for this vaccine, but there are published studies suggesting that underreporting is about 10% of adverse events are actually reported. So that being the case, I think we need to be very careful and also have access to data that we probably wouldn't ordinarily have.

[3:33:06]
And that is I'm very interested in learning more about what we now know through animal studies, the studies that we would typically have for preclinical trial data, the reproductive toxicity data, the, you know, various biodistribution studies. I think this would maybe help to sort out some of the confusing information that we have. Thank you very much.
[Dr. Sarah Meyer]
Do you want to?

Response on VAERS Underreporting for Serious Adverse Events

Could I make a comment? I just wanted to respond to your concern about VAERS underreporting. And what I just wanted to share is that some of those reports suggesting vast underreporting in VAERS are inclusive of things like sore arm, rash, things that people don't normally report to VAERS.

[3:34:03]
So I'm not sure about anyone here, but I never reported to VAERS when I had a sore arm last time for vaccination. But CDC has conducted a number of studies that we have published in the literature that shows that for serious adverse events, the reporting rate to VAERS is much higher. So it's up to 76% for anaphylaxis, depending on the vaccine, up to 64% for Guillain-Barre syndrome, again, for, you know, but depending on the vaccine. We've looked at this for in a susception following rotavirus vaccine, vaccine associated polio following polio vaccination. So I think I just wanted to point out that for serious reports, we are confident that we get a majority of those reported to VAERS.
[Dr. Rezif Levy]
Dr. Lieber?

Comment from Dr. Levi on Myocarditis Reporting and Serious Adverse Events

First, this is very useful information. I still think that there are, if I take the myocarditis example, I still think that we probably have, we can see if we actually compare the rates in based on VAERS versus the rates based on clinical diagnosis versus the rates based on actually testing the troponin levels of people before and after vaccination, we see underreporting depending on the system you're using.

[3:35:21]
And VAERS is probably still underreporting it, maybe not to the extent of 10%. And the other thing that I think that we, if I understand correctly the data, we do see in VAERS some serious adverse events and some actually new ones that are being reported at rates that are far exceeding other vaccines, even when you normalize to the number of doses, which does suggest something, I think.

Conclusion of COVID-19 Session and Next Steps

[Dr. Martin Kulldorff]
Thank you. So we are behind time, so I think we're going to continue. And Dr. McNeil, please, for the last presentation of evidence to recommendations.
[Ben Spader]
Sure. Thank you. I'll now briefly wrap up the COVID-19 session and discuss the evidence to recommendations for the 2025-2026 COVID-19 vaccination.

[3:36:13]
And in my energy, I did not even wait for the slides to pull up.

Evidence to Recommendations Framework for 2025-2026 COVID-19 Vaccination

This slide shows the evidence to recommendations framework, including the domains of public health problem, benefits and harms, values, acceptability, feasibility, resource use, and equity, as well as their associated questions. The first two domains were presented to the workgroup for review and discussion. The rest of the ETR and final polling was planned for the final workgroup call.

Workgroup Review of Domains

[3:37:07]
The workgroup has continuously reviewed data on the public health problem and the benefits and harms domains, and most recently reviewed a summary of the domains during the May 29th and June 5th workgroup calls. As these domains are primarily informed by the epidemiology, vaccine effectiveness, and safety presentations, data reviewed by the workgroup in these domains was incorporated into the previous presentations.

Summary of Workgroup Considerations (Public Health Problem)

On June 12th, the workgroup was planning to discuss the additional evidence to recommendations framework domains and participate in final polling before the ACIP meeting. Because the workgroup call was not convened, ETR was not able to be finalized, and the workgroup did not undergo final polling. As a summary of the workgroup considerations around the public health problem, burden from COVID-19 has been trending down year over year since 2001, but substantial morbidity and mortality continues to occur.

[3:38:12]
Higher rates of COVID-19 hospitalization and deaths, in particular in the oldest and youngest age groups with the highest rates in adults aged greater than 65 and infants ages six months and less. Children less than two years of age have the highest morbidity and mortality of all pediatric ages, but deaths due to COVID-19 can occur at any age. Paternal vaccination is the best protection against COVID-19 for pregnant women and infants less than six months of age who are too young to be vaccinated. Finally, as a summary of the workgroup considerations around benefits and harms, the 2024-25 COVID-19 vaccination is effective in preventing hospitalizations and critical outcomes from COVID-19 in adults.

Summary of Workgroup Considerations (Benefits and Harms)

[3:39:06]
Data from prior vaccine formulations show that vaccine effectiveness has been similar across age groups. COVID-19 vaccines have been continuously monitored through bus safety surveillance, which identified and characterized the risk of myocarditis and pericarditis after mRNA COVID-19 vaccination. No other risks have been confirmed in the current U.S. licensed vaccines except those typically seen with other vaccines, such as local and systematic reactions and allergic reactions. Pregnant women are at an increased risk of severe disease and adverse pregnancy outcomes from COVID-19. Maternal vaccination has been shown to protect infants less than six months of age from severe outcomes of COVID-19 vaccine. I would again like to extend my thanks to all the CDC and external collaborators who contributed to these presentations.

Acknowledgments

Thank you.

Conclusion of COVID-19 Session

[Dr. Martin Kulldorff]

[3:40:02]
Thank you so much for all these presentations and for a lively discussion, for all the comments and questions. There is no vote scheduled to be held on this topic, and I think as the ACIP, we look forward to receiving the report from the working group before the next meeting. And this has been extremely informative for all of us, so we thank all the CDC presenters and also everybody behind those presentations because there are a lot of people working on that. So thank you very much. And we are half an hour behind schedule, so I think we're going to take a lunch break now.

Lunch Break Announcement

It will take half an hour as planned, and then we will reconvene here at 2 p.m. So thank you so much, everybody.
[Dr. Mina Zadeh]
Thank you. And when we come back for our records, I'll have to do a roll call for our liaisons and our ex-officio, so I'll do that at that time.

[3:41:05]
Thank you.

Roll Call Reminder

Reconvene and Agency Updates

[Dr. Martin Kulldorff]

[4:20:18]
So I hope you all had a great lunch. And we are now going to continue with agency updates.
[Dimitri Daskalakis]
So please.
[Dr. Mina Zadeh]
We'll start with CDC.

CDC Update

[Dimitri Daskalakis]
Good afternoon, and welcome back from lunch. Thank you for the opportunity to give you an update about the CDC. My name is Dimitri Daskalakis from the National Center for Immunization and Respiratory Diseases, and I'll be splitting this update with Chris Braden from the National Center for Emerging Zoonotic Infectious Diseases. So just briefly, I think you all, many of you are familiar, but just to quickly orient you, the National Center for Immunization and Respiratory Diseases, its mission is to prevent disease, disability, and death through immunization and by control of respiratory and related diseases.

[4:21:09]
So we can always go for a much deeper dive at another time where there is more time, but instead I'm going to focus on a couple of the outbreaks that we are currently working on domestically. And so the first is the measles outbreak.

Measles Outbreak Update

As of today, CDC has reported 1,227 measles cases from 37 U.S. jurisdictions in 2025. There have been 23 outbreaks reported in 2025, and 89% of the cases of measles have been associated with those outbreaks. One specific outbreak really makes up the lion's share of infections. This is the outbreak that is occurring in the southwest, with Texas reporting 750 cases across 35 counties and New Mexico reporting 81 total cases, primarily in the southwestern part. There's some really good indicators that we have hit a plateau. The cases are definitely decreasing.

[4:22:00]
So as we are seeing fewer cases in the southwest, we continue to see global introductions that come into the U.S., which thankfully to date have mainly been like short terminal chains of transmission as opposed to more sustained transmission like we saw in the southwest. So our overall risk to the U.S. population is low, but we continue to have vigilance around mobility as well as populations who may not be immune. I also want to briefly highlight H5N1, affectionately called bird flu.

H5N1 (Bird Flu) Update

So H5N1, as you may recall, is an outbreak that mainly affects animals. So historically, since the 90s, H5N1 has been seen in birds and there has been spillover into poultry, so domestic, more like commercial birds. Last year, we also had the introduction of this virus into cows with a pretty significant, that's a new mammalian species that had not experienced H5N1 in the past, resulting in over 1,000 herds being diagnosed with H5N1 and spillover to humans with 70 cases reported.

[4:23:15]
The folks who were at the highest risk for that infection were people who were working closely with animal or animal products or had exposures to birds, including backyard flocks. So we have the good news that we are seeing overall a decrease in the number of infections that are being detected in non-human mammals and in birds. Specifically, a huge shout out to our USDA colleagues who are doing bulk milk testing that is detecting cases in herds earlier. The effect of that has been that to date, we have had no new human cases in over 15 weeks, which I think is great news despite ongoing monitoring by local health departments. And then lastly, a lot of what we're going to be talking about in the next couple of days focuses on respiratory viruses that are important to seasonal preparedness.

[4:24:05]
So we at NCIRD are responsible for the seasonal outbreak that we see every year that you've already heard in such detail about COVID.

Seasonal Respiratory Viruses

You'll hear more about flu and RSV. So we continue to work to make sure that we provide Americans the best tools to be able to prevent these infections. With that, I'll hand it over to Chris Braden. And I think we'll defer to the chair to see if we take questions now or later.
[Dr. Martin Kulldorff]
No, right now we're asking to do the presentations from the different agencies.
[Dimitri Daskalakis]
Chris, do you want to?
[Chris Braden]
Yeah, so I'll be very brief.

NCEZID Update (Chris Braden)

My name is Chris Braden. I'm the principal deputy director for the National Center for Emerging and Zoonotic Infectious Diseases. There are over 800 pathogens that we're responsible for, some of which you know well, and some of which are very exotic. For along the lines of the outbreaks that we are working on right now, there's a number of foodborne outbreaks that we're detecting through a system called PulseNet, which uses whole genome sequencing to match isolates that likely have a common source.

Foodborne Outbreaks

[4:25:08]
We are looking at salmonella infections linked to pistachio cream right now. Again, these are multistate and also to eggs. Interestingly, we have a cluster of illnesses due to Botox injections.

Botox Injections Cluster

We're working with Massachusetts to investigate this cluster of illnesses. These are injections that cause a systemic illness beyond the injection site. It looks to be due to a unlicensed provider and an unlicensed facility that is providing Botox injections. We get heavily involved because CDC is the source of the botulinum antitoxin. The antitoxin is stored in port health stations that CDC runs around the country, and we provide that for clinical care, and we do consultations on all of these types of illnesses in addition to the epidemiologic investigation.

New World Screwworm

[4:26:03]
One other thing that I'll just say that emphasizes the zoonosis aspect of our work is New World Screwworm, which is making its way up from Central America into Mexico right now. It is mainly an animal disease. It is led, investigation is led by USDA, but we, there is a human component where New World Screwworm can cause a very nasty meiosis that is basically an infestation of the maggots in skin and so forth, and they eat the live tissue. So, that always is a little bit impressive. We're working with USDA on that. It is a threat right now to mostly animal agriculture, some human component in the United States as it makes its way up from Central America and Mexico. I'll stop there. Happy to talk about any of these subjects at another time. Bye.
[Dr. Martin Kulldorff]
Thank you.

CMS Update

And the next. CMS. If you have nothing, that's perfectly fine.

[4:27:14]
Okay.

FDA Update (Tracy Bethel Hoag)

[Dr. Tracy Beth Hoag]
FDA. Yeah. Hi. Tracy Bethel with the FDA. Just a few updates. I actually think I'm going to start with an update related to a question that was brought up that I'll address briefly, which is related to an announcement today of a safety label change to the mRNA vaccines reflecting the risk of myocarditis.

Safety Label Change for mRNA Vaccines (Myocarditis)

And part of it is based on a question from Dr. Meisner related to Sarah Meisner's, Sarah in 2023 and 2024, the best data, the FDA's best data, we did find a 27 per million rate of myocarditis after the mRNA vaccines in 12 to 24-year-old males and the safety label change is going to reflect this.

[4:28:05]
I wanted to differentiate that from the CDC data that was presented before that, which was not stratified in that age group or by sex. And that present, that also had a lower rate of two per million. And so, we think that the FDA best data is best to use for the males 12 to 24, shows an ongoing risk in the 2023-2024 season that we saw, as well as concern about ongoing myocardial damage that was seen with late gadolinium enhancement or MRI imaging about a half a year after, about a half a year after vaccination with uncertain clinical significance. But because of that, we did, we did announce that there was a safety label change today to the mRNA vaccines. In other news, you probably are all familiar with, it was discussed, VRBPAC, our VRBPAC did recommend the JN1 antigen, which was interestingly consistent with the year before reflecting the slower rate of viral mutation that we have been discussing.

VRBPAC Recommendation and New Regulatory Framework

[4:29:18]
And at the FDA, we also announced a new regulatory framework, which many of you are familiar with, and Nuvavoxid and MnExpike were approved with the narrowed indication for 12 to 64 years with one risk factor for severe COVID-19 and then 65 years and older. That was for Nuvavoxid, as well as a post-marketing commitment to a randomized control trial, placebo-controlled in adults ages 50 through 64. So, we hopefully are going to get some better, higher quality data about current efficacy of the vaccines, and that commitment was, that was also given for the MnExpike vaccine, which is indicated in those with prior vaccination and, again, ages 12 and older, 12 to 64 with one risk factor for severe COVID-19 and then ages 65 and older.

[4:30:17]
And then, we also had, there was an issue that many of you are probably familiar with, with the Ixchik vaccine that there was a, the FDA put a pause on that for adults ages 60 and older due to 17 adverse events and two deaths.

Ixchik Vaccine Pause

And this is the live chikungunya vaccine. And, oh, and then related to the myocarditis, there was a question that came up from Dr.

Subclinical Myocarditis Study

Meissner that I just wanted to address right now, and this is, it is FDA-related about the subclinical myocarditis, that there was a study that came out by Albertson et al that did address

[4:31:01]
one of the post-marketing requirements in 5- to 30-year-olds that was published in Infectious Diseases and Therapy, and we could hold an entire journal club on that article, but I wanted to make Dr. Meissner aware of that study.
[Dr. Mina Zadeh]
Thank you. Health Resources and Services Administration.

Health Resources and Services Administration Update

Anyone on the line?
[Dr. Sandra Fryhofer]
Hi, good afternoon. This is Commander Britt Rizk with HRSA, and we have no updates at this time. Thank you.
[Dr. Mina Zadeh]
Thank you. Indian Health Services.

Indian Health Services Update

[Dr. Matthew Clark]
Hi, good afternoon. It's Dr. Matthew Clark. The Indian Health Service is working closely with our federal, tribal, and our urban Indian organization partners to mitigate the risk of vaccine-preventable illness in our vulnerable service population. In accordance with our mission, IHS is committed to raising health status and improving health outcomes in American Indian and Alaska Native tribal communities across a wide spectrum, from the promotion of healthy lifestyles to screening and prevention, support of traditional culture and healing, and effective management of both acute and chronic diseases.

[4:32:11]
As a comprehensive healthcare system for 2.1 million American Indian and Alaska Native beneficiaries, vaccination is a key component to this broader strategy. We seek to advance this strategy through proactive education, proper informed consent, and respect for patient, family, and community values and priorities. Tribal communities face many unique challenges that impact access to effective preventive clinical and public health interventions. IHS is actively working with our tribal and tribal health partners to identify vaccine prevention priorities and to establish vaccine best practices that meet the current needs of Indian Country. Thank you.
[Dr. Mina Zadeh]
Thank you.

National Institute of Health Update

National Institute of Health.
[Dr. Joseph Hiblin]
Thank you. Mike Carrillo from NIH.

[4:33:00]
No updates to report at this time.
[Dr. Mina Zadeh]
Thank you.

Liaison Roll Call

And now I'll have to do the roll call for our liaisons. I'll try to do it as quickly as possible. American Academy of Family Physicians.

American Academy of Family Physicians

[Lexi Jones-Packham]
Good afternoon.
[Dr. Laura Morris]
It's Dr. Laura Morris from University of Missouri representing AAMP.
[Dr. Mina Zadeh]
Thank you. American Academy of Pediatrics.

American Academy of Pediatrics

Okay. American Academy of Pediatrics. Okay.

American Academy of Physician Associates

American Academy of Physician Associates.
[Michelle Lege]
My name is Michelle Lege, Director of Clinical Education at AAPA.
[Dr. Mina Zadeh]
Thank you. American College of Health Association.

American College of Health Association

[Ashley Halberner]
Hi. Ashley Halberner from the American College Health Association.
[Dr. Mina Zadeh]
American College of Nurse Midwives.

American College of Nurse Midwives

[Ashley Halberner]
Carol Hayes, present.
[Dr. Mina Zadeh]

[4:34:04]
American College of Obstetrics and Gynecologists.

American College of Obstetrics and Gynecologists

[Dr. Link-Gelles]
Hi. This is Dr. Naomi Joseph, Internal Fetal Medicine Physician representing the American College of Obstetrics and Gynecologists.
[Dr. Naomi Joseph]
And I just want to take this moment to thank you all for the invitation and for having this presentation with me today. And especially want to thank Dr. McNeil and members of the CDC for unequivocally presenting the risk of COVID-19 disease to pregnant women and their infants and the robust data that's regarding their safety of immunization.
[Marcia Cohen-Sakai]
Over.
[Dr. Mina Zadeh]
Thank you. American College of Physicians.

American College of Physicians

American Geriatrics Society.

American Geriatrics Society

[Ben Spader]
Ben Spader here for AGS. Thank you.

America's Health Insurance Plans

[Dr. Mina Zadeh]
America's Health Insurance Plans. American Immunization Registry Association.

American Immunization Registry Association

[Dr. Vicki Pepsworth]

[4:35:02]
Good afternoon.
[Dr. Georgina Peacock]
Rebecca Quayle representing ARAP.
[Dr. Mina Zadeh]
Thank you. American Medical Association.

American Medical Association

[Dr. Sandra Fryhofer]
Dr. Sandra Fryhofer representing the American Medical Association.
[Dr. Mina Zadeh]
Thank you.

American Nurses Association

American Nurses Association.

American Osteopathic Association

American Osteopathic Association. American Pharmacists Association.

American Pharmacists Association

[Dr. Sandra Fryhofer]
Good afternoon. Dr. Kelly Goode representing the American Pharmacists Association.
[Dr. Mina Zadeh]
Thank you.

Association of Immunization Managers

Association of Immunization Managers.

Association for Prevention, Teaching, and Research

Association for Prevention, Teaching, and Research.
[Dr. Matthew Clark]
Richard Zimmerman representing APTR at present.
[Dr. Mina Zadeh]
Thank you. Association of State and Territorial Health Officials.

Association of State and Territorial Health Officials

[Michelle Lege]

[4:36:01]
Good afternoon.
[Lexi Jones-Packham]
This is Erika McGowan, Senior Director of Emerging Infectious Diseases representing ASCO, standing in for Dr. Nimesha Jatara.
[Diana Figueroa]
Thank you. Over.
[Dr. Mina Zadeh]
Thank you.

Biotechnology Innovation Organization

Biotechnology Innovation Organization.
[Ashley Halberner]
Good afternoon. Phyllis Arthur and Emily Acker for Biotechnology.
[Dr. Mina Zadeh]
Thank you. Council of State and Territorial Epidemiologists.

Council of State and Territorial Epidemiologists

[Dr. Christine Hahn]
Dr. Christine Hahn representing CSDE.
[Dr. Mina Zadeh]
Thank you. Canadian National Advisory Committee on Immunization.

Canadian National Advisory Committee on Immunization

[Eric Weintraub]
Hello. Matthew Tunis Bernassi.
[Dr. Mina Zadeh]
Infectious Disease Society of America.

Infectious Disease Society of America

International Society for Travel Medicine.

International Society for Travel Medicine

National Association of County and City Health Officials

National Association of County and City Health Officials.
[Dr. Joseph Hiblin]
This is Matt Zahn representing the HO at present.
[Dr. Mina Zadeh]
Thank you. National Association of Pediatric Nurse Practitioners.

National Association of Pediatric Nurse Practitioners

[Ashley Halberner]

[4:37:03]
This is Dr. Stacey Buchanan, a doctorally prepared nurse practitioner representing NACNAP, a science-based membership organization of over 8,000 APRNs caring for children.
[Dr. Mina Zadeh]
Thank you. National Foundation for Infectious Diseases.

National Foundation for Infectious Diseases

[Dr. Link-Gelles]
This is Dr. Bob Hopkins and Marla Dalton for NFID, supporting preventive health for all Americans.
[Dr. Mina Zadeh]
Thank you.

National Medical Association

National Medical Association.

Pediatric Infectious Diseases Society

Pediatric Infectious Diseases Society. Pharmaceutical Research and Manufacturers of America.

Pharmaceutical Research and Manufacturers of America

[Dr. Matthew Clark]
Yeah, thanks. This is Dr. Michael Ibarra.
[Dr. Vicki Pepsworth]
I'm an emergency physician and chief medical officer representing pharma. Thank you.
[Dr. Mina Zadeh]
Thank you. Society for Adolescent Health and Medicine.

Society for Adolescent Health and Medicine

Society for Healthcare Epidemiology of America

[4:38:00]
Society for Healthcare Epidemiology of America. Thank you. Society for Healthcare Epidemiology of America. Okay, I think that was the last one.

Unmuted Liaisons

Is there anyone else that did not get to introduce themselves?
[Dr. Link-Gelles]
Some people are trying to introduce themselves. American College of Physicians, but his mic is not working.
[Dr. Mina Zadeh]
Okay.
[Dr. Christine Hahn]
And this is Molly Howell representing the Association of Immunization Managers.
[Dr. Sandra Fryhofer]
My mic was also not working.
[Dr. Mina Zadeh]
Okay, thank you. I think that's it.

Conclusion of Roll Call

[Dr. Martin Kulldorff]
Thank you for that, and I appreciate all your participation in this meeting.

RSV Vaccine Session Introduction (Maternal and Pediatric)

We will now move on to discussing the RSV vaccine, maternal and pediatric. And to introduce that, Dr. Adam McNeil, please.
[Ben Spader]

[4:39:02]
Good afternoon. My name is Adam McNeil, so I'm the acting division director for the coronaviruses and other respiratory viruses division within CDC. I'm now going to introduce the maternal and pediatric RSV session. Before I begin, I would like to mention that there are also RSV vaccines for adults. The policy for these vaccines is considered by a separate work group, and it is not covered in this session. Also, just a reminder, all slides are publicly available on the ACIP website.

Burden of RSV in Infants

RSV infection is the leading cause of hospitalization in U.S. infants. RSV can infect the small airways in the lungs. Most infants are infected in the first year of life, and nearly all are infected by age 2. Two to 3% of young infants are hospitalized for RSV. Roughly 80% of children who are hospitalized for RSV have no underlying medical conditions.

[4:40:01]
In short, all young infants are at severe risk for RSV.

New Prevention Products in 2023

Prior to 2023, no long-acting products were available for their prevention of severe RSV disease. In 2023, two products for prevention of severe RSV disease in infants were approved by the FDA and subsequently recommended by CDC and ACIP.

Clostrovimab Introduction

CDC and ACIP recommend that all infants be protected against severe RSV disease with either maternal RSV vaccine or infant immunization. I'm not hearing anything.

Audio Issues

Is the room muted? I've lost audio as well.
[Dr. Vicki Pepsworth]
I've also lost audio. Same here, no audio.
[Eric Weintraub]
Lost audio as well.
[Ben Spader]
I'll speak again from the microphone. Can you hear me? Maybe also if the chair could sound check whether it's his microphone or the entire room.
[Chris Braden]

[4:41:01]
We can hear you now.
[Ben Spader]
Thanks. And can I ask, did you hear the start of the presentation or should I loop back to the beginning?
[Speaker 31]
Go back to the beginning.
[Ben Spader]
Sorry, was that beginning?
[Speaker 31]
Yes.
[Ben Spader]
Okay, thank you. Good afternoon.

RSV Vaccine Session Introduction (Audio Restored)

My name is Adam McNeil. I am the Acting Division Director for the Coronaviruses and Other Respiratory Viruses Division within CDC. Before I begin, I would like to mention that in addition to the maternal RS, maternal and pediatric RSV session, which we will discuss here, there is also a separate RSV vaccine for adults. This is considered by a separate work group and will not be covered in this session.

[4:42:02]
Also, just a reminder, all slides are publicly available on the ACIP website. Next slide.

Burden of RSV in Infants (Continued)

RSV infection is the leading cause of hospitalization in U.S. infants. RSV can infect the small airways in the lungs. Most infants are infected in the first year of life and nearly all are infected by age two. Two to three percent of young infants are hospitalized for RSV. Roughly 80 percent of children who are hospitalized for RSV have no underlying medical conditions. So in short, all young infants are at severe risk for RSV. Prior to 2023, no long-lasting products were available for prevention of severe RSV disease.

Prevention Products and Recommendations

In 2023, two products for prevention of severe RSV disease in infants were approved by FDA and subsequently recommended by CDC and ACIP.

[4:43:02]
CDC and ACIP recommend that all infants be protected against severe RSV disease, either through maternal RSV vaccination or receipt of monoclonal antibodies to an infant. For infants, there are two immunizations, a maternal vaccine and a long-lasting monoclonal antibody. All infants are recommended to be protected against severe RSV disease by either the maternal RSV vaccine or Nirsevimab. Only one is needed in most instances. Pregnant women should get a single dose of maternal RSV vaccine during weeks 30 through 32 through 36 weeks of pregnancy. Nirsevimab is recommended for infants younger than eight months or are born during or in their first RSV season. Nirsevimab is also recommended for some children aged eight through 19 months who are at increased risk for severe RSV disease during their second RSV season.

Clostrovimab Review Process

[4:44:09]
Today, we'll be reviewing data on a new long-lasting monoclonal antibody, Clostrovimab, that would become a third option to protect infants from severe RSV disease if approved. Clostrovimab was approved by the FDA on June 9, 2025, for infants born during or in their first RSV season. The Maternal Pediatric Workgroup and ACIP review of data on Clostrovimab has been ongoing since September 2023. In September, excuse me, since September 2024. In September 2024, the Maternal Pediatric RSV Workgroup reviewed and discussed data from Merck on safety and efficacy of Clostrovimab. In October 2024, ACIP further reviewed and discussed data from Merck on safety and efficacy of Clostrovimab and the workgroup interpretation of these data.

[4:45:07]
During November 2024 to April 2025, the Maternal Pediatric RSV Workgroup reviewed and discussed grade, the grading of recommendations, assessment, development, and evaluations of the evidence for Clostrovimab, evidence to recommendation, and the evidence to recommendations framework for Clostrovimab.

Workgroup Review of 2024-2025 Season Data

Today, I will represent these data and their interpretation for the committee. Since the April 2025 ACIP meeting, the workgroup has also reviewed data on the uptake safety and effectiveness of maternal RSV vaccine and long-lasting antibody from the 2024-2025 season. During today's session, these data will be presented to the committee along with the workgroup interpretation.

Session Presentations

[4:46:01]
This session will include five presentations. The first three presentations will cover updates on products currently in use, including uptake of maternal RSV vaccine and long-lasting monoclonal antibody, effectiveness, impact, and safety of maternal RSV vaccine and long-lasting monoclonal antibody. Then the final two presentations will include the evidence to recommendation framework for Clostrovimab and the workgroup interpretations.

Maternal RSV Uptake and Implementation Presentation

I will now pass it off to Georgina Peacock, who will present on maternal RSV uptake of maternal RSV vaccine and Nirsevimab.
[Dr. Georgina Peacock]
Thanks, Dr. Neal. And just as a reminder, I'm the Division Director for the Immunization Services Division. And today, I'll be talking about the implementation and uptake of Nirsevimab and maternal vaccination for infant protection from RSV.

[4:47:03]
Before I do that, just a follow-up to a question you had earlier on our healthcare provider vaccination coverage for COVID.

Follow-up on Healthcare Provider Coverage

Those data are not available yet for this season, but we can have those at a subsequent meeting. All right.

Data Sources for Presentation

Just to review the data sources that I'll use in this presentation, as I highlighted during the COVID presentation, the Immunization Services Division obtains data on vaccination coverage and other information on immunization implementation from multiple sources. First, as I already stated, the National Immunization Survey is a random-digit-dialed cellular telephone survey for adults 18 years and older in the United States, local jurisdictions, and associated territories.

[4:48:01]
Second are the Immunization Information Systems. These are confidential, population-based, computerized databases that record all immunization doses administered by participating providers to persons residing within a given geographic area. And since 1993, CDC has funded 64 U.S. jurisdictions to implement IISs. We receive monthly aggregate data for COVID influenza and RSV and quarterly line-level de-identified data for individual immunizations. And third, the Vaccine Safety Data Link, which you heard referred to by Dr. Meyer earlier, provides estimates of vaccination coverage based on electronic health data. For purposes of this presentation, VSD provides us with maternal vaccination coverage.

Coverage for Nirsevimab and Maternal Vaccination

And now for some information on coverage for nircivimab and maternal vaccination.

Nirsevimab Administration by Month

[4:49:00]
These data, drawn from the Immunization Information Systems, illustrate the administration of nircivimab by month of receipt among infants under eight months of age. During the second season of availability, so the 2024-25 season, more infants received protection against RSV through nircivimab administration than in the first season, 2023-2024. This slide is the first of two consecutive slides showing infant age at the time of nircivimab receipt, stratified by birth month.

Infant Age at Nirsevimab Receipt (2023-2024)

This slide is for the first season of implementation, so the 2023-24 season. And the pale blue colors indicate receipt of nircivimab closer to birth. The darker blue color indicates receipt of nircivimab more than one month after birth. Infants born during the RSV season, so from October to March, received their dose of nircivimab closer to birth than infants born before September, which is what we would expect with nircivimab, as it's only recommended and available in most states shortly before the RSV season begins.

Infant Age at Nirsevimab Receipt (2024-2025)

[4:50:15]
This slide, again, shows receipt of nircivimab by birth month, but for the second season of implementation. For infants born during the RSV season, more received nircivimab within the first month of life than in the 2023-24 season, showing increased healthcare provider understanding of the appropriate administration guidance, as well as improved access to nircivimab. This slide shows the percent of pregnant women ages 18 to 49 years vaccinated with RSV vaccine overall and by race and ethnicity during the 2024-25 respiratory season, using data from the CDC's vaccine safety data link.

Maternal RSV Vaccination Coverage

We see that from September 2024 through January 2025, 38.5% of pregnant women were vaccinated overall.

[4:51:08]
Vaccination coverage ranged from 25.7% among black pregnant women to 52.6% among Asian pregnant women. This is fairly consistent with other vaccines during pregnancy, where we typically see the highest coverage among Asian non-Hispanic and white non-Hispanic women and lowest coverage among black non-Hispanic and Hispanic Latino women. This slide shows the percentage of infants less than eight months during the respiratory virus season, born since April 2024, who were protected by either maternal vaccination in the dark blue color or nircivimab in the light blue color, using data from the National Immunization Survey Fall Respiratory Virus Module.

Infant Protection by Maternal Vaccination or Nirsevimab

Data were reported by women 18 to 49 years who had a baby born since April 2024, and the x-axis represents month of interview.

[4:52:05]
So, when we look at the most recent month, March 2025, we can see that those surveyed who had an infant born since April 2024, 12.3% of mothers received RSV vaccination during pregnancy, and for these, their infant did not receive nircivimab, and 44.7% of infants received nircivimab. Therefore, by March of 2025, 57% of infants born between April 2024 and March 2025 were protected by either maternal vaccination or receipt of nircivimab. And so, now I'll move to talking a little bit about some implementation that we've done, particularly around birthing hospital enrollment in the Vaccines for Children program to facilitate nircivimab administration.

Implementation Around Birthing Hospital Enrollment in VFC

So, as a pediatrician, I've experienced the impact of RSV in infants, and I remember admissions when I was a pediatric resident where we had too many infants that we were admitting overnight, and in fact, even had to lifelight some babies to other states and other hospitals for care, and because there weren't enough beds and there weren't enough staff to care for them.

[4:53:23]
So, both the maternal vaccine and the RSV monoclonal antibody are really life-saving and prevent hospitalizations, and the CDC, together with our state immunization programs, has worked really hard to ensure that critical therapeutics are available for newborns as soon as they become eligible.

Role of Birthing Hospitals

Since nircivimab is recommended within the first week of life for children born in October through March in most of the continental United States, birthing hospitals play a key role in ensuring newborn children receive nircivimab to protect them against RSV.

[4:54:00]
Children who lack commercial insurance coverage, approximately 45 percent of children ages 0 to 17 years in the United States, are less likely to be seen by a primary care physician within one week of birth than children who have commercial insurance. Therefore, it's important to have an option in the birthing hospital. Birthing hospitals play a vital role in ensuring that there are no missed opportunities for RSV immunization before hospital discharge and coordination of care with pediatricians. So, birthing hospital participation in VFC program promotes access to all ACIP recommended vaccines.

Benefits of Birthing Hospital Participation in VFC

It enables newborns to receive the immunizations they need before hospital discharge and reduces hospital's upfront costs since hospitals do not have to pay for the nircivimab or the hepatitis B vaccines for VFC eligible children. It also helps provide quality care to all infants who are at risk for RSV infection regardless of insurance status.

Increase in Birthing Hospitals Enrolled in VFC

[4:55:21]
So, when nircivimab was added to the routine childhood immunization schedule in 2023, 292 of the 2,827 U.S. birthing hospitals were enrolled in the VFC program. So, approximately 10 percent. Enrolling birthing facilities into the VFC program has required updated policy approaches, new partnerships, and intense communication on the importance of birthing hospitals playing a part in infant RSV prevention. Through the hard work and dedication of our immunization programs and other partners, we've increased the number of birthing hospitals enrolled in VFC from 292 to over 1,000 birthing hospitals, a substantial increase in less than two years.

[4:56:14]
And so, now a little bit about our plans for the 25-26 season of RSV monoclonal antibody administration in the VFC program.

Plans for 2025-2026 RSV Monoclonal Antibody Administration

We anticipate the supply will be sufficient to meet demand and will also be available earlier than last season. Earlier supply enables broad availability prior to the start of immunization and promotes confidence in the program implementation. So, in particular, we've been working with our state partners and professional organizations as well as with the Indian Health Service to improve access and uptake of both maternal vaccine and infant monoclonal antibodies. CDC will facilitate availability of RSV monoclonal antibody across jurisdictions, ensuring that each jurisdiction has access.

[4:57:06]
And preseason technical assistance is happening right now around ordering so that we can ensure that the whole process works well. We expect increased availability of 50-milligram doses of nircivumab at the beginning of the season compared to last season, and the newly licensed clozirovumab can be available once it has been added to CDC's VFC contracts.

Summary of Uptake and Implementation

So, in summary, in the 2024-25 season, more infants who were born during the RSV season and received nircivumab did so in the first month of life compared to those born in the prior season of administration, so 2023-24. Likely due to increased healthcare provider awareness as well as consumer or family awareness as well as a greater availability of supply.

[4:58:01]
Maternal immunization and RSV monoclonal antibodies protected 57 percent of infants born April 2024 to March 2025, showing the benefit of offering both options. Increased birthing hospital enrollment and improved early supply of RSV monoclonal antibodies should provide greater access to protection from RSV in this upcoming season. Thanks very much. And so I'll turn it back to Dr. McNeil.

Continuation of Presentations

[Dr. Martin Kulldorff]
Yeah, I think in the interest of time, I think we can just continue with the next presentation and then we can save questions for a little bit later.
[Dr. Mina Zadeh]
Okay.
[Ben Spader]
Good afternoon.

Effectiveness and Impact of Nirsevimab and Maternal RSV Vaccination

We will provide an update on the effectiveness and impact of nircivumab and maternal RSV vaccination in infants during the 2024-25 RSV season.

[4:59:01]
I will briefly summarize how we assess product effectiveness and the systems used at CDC for these analyses. I'll then provide a summary of the observed effectiveness of nircivumab and the maternal RSV vaccine during the 2024-25 respiratory season in the United States and provide a summary of systems used for monitoring RSV hospitalization rates and the observed impact of these prevention products.

Overview of Effectiveness Assessment Methods

So first, overview of how CDC assesses product effectiveness in the United States. There are several study designs that can be used for product effectiveness assessment. All three data sources I'll be discussing today use a variation of the case control design, as we've discussed this morning. Two systems, VISION and NVSN, use a test-negative design. In this design, infants who receive care for acute respiratory illness will be tested for RSV and are tested for RSV are included.

[5:00:03]
Our third platform, Overcoming Network, utilizes a matched case control design, where prevention product receipt is assessed for children who are RSV positive and compared with matched children who do not have RSV. For the data I'll present today, the product effectiveness is estimated by comparing the odds of immunization in infants who are RSV positive with the odds of immunization in infants who are RSV negative. Here are a few more details for each of the three CDC platforms that we have used to assess RSV prevention product effectiveness in the United States.

Product Effectiveness Estimation

CDC Platforms for Effectiveness Assessment

All three have different strengths and limitations. VISION is a multi-site electronic health record system, including visits from 160 emergency departments and 131 hospitals in six states. NVSN is an active surveillance network for acute respiratory illness in children at seven pediatric academic health systems.

[5:01:05]
And the Overcoming Network conducts active surveillance for infants with RSV in critical care settings in 26 pediatric intensive care units in 23 states.

Data and Definitions Used by Platforms

In this table, I briefly summarize the data and definitions used by each of these three platforms. All three platforms have a multi-step review process to verify immunization status, including electronic health records and immunization registries. For VISION and NVSN, the analytic study period for the product effectiveness I'll present today is from October 2024 to March 2025. The overcoming study period is December 2024 to April 2025. For all studies, cases consist of children testing positive for RSV and a clinical RSV test. NVSN systematically tests all enrolled children for RSV, and thus cases may include children who did not receive clinical testing.

[5:02:04]
Children or controls are children who test negative for RSV. For NVSN, this may include children who were not tested clinically. Importantly, the Overcoming Network enrolls match controls based on site, age, and data hospitalization of cases. For the Nusabimab analyses, all studies included infants if they were eight months old on October 1st, 2024, or born after October 1st during the study period. The maternal vaccine analysis for VISION included infants born on or after September 14th, 2024, which is 14 days after maternal RSV vaccine availability in most of the United States, while the NVSN analysis included infants less than six months of age during the study period. All analyses used multivariable logistic regression, adjusting for site, age in months, and timing of enrollment.

[5:03:04]
VISION also adjusted for race, ethnicity, and sex. For Nusabimab effectiveness analyses, NVSN and Overcoming also adjusted for presence of at least one high-risk medical condition for severe RSV disease.

Nirsevimab Effectiveness Against ED Visits

Overcoming also adjusted for social vulnerability index. NVSN also adjusted for race and ethnicity and insurance status for maternal RSV vaccine effectiveness analysis. Moving on to results, first I'll present the assessment of Nusabimab effectiveness during the 24-25 RSV season in the United States. This slide summarizes the effectiveness of Nusabimab against RSV-associated emergency department, or ED, visits in infants during their first RSV season from VISION and NVSN.

[5:04:03]
The table includes the number of children by Nusabimab and RSV status, median days since dose among those who are immunized, and adjusted product effectiveness. The data are presented by platform with VISION data on the top and NVSN data on the bottom. Among over 4,000 ED visits in children included in the VISION analysis, 79% of RSV-positive children did not receive Nusabimab compared to 64% among RSV-negative children. Similarly, among nearly 500 ED visits in children included in the NVSN analysis, 86% of RSV-positive children did not receive Nusabimab compared to 56% among RSV-negative children. Among children that had received Nusabimab, the median time since dose for both networks was 68 days at the time of their ED visit. The estimated adjusted product effectiveness against RSV-associated ED visits was 63% in VISION and 76% in NVSN, with 95% confidence intervals for both point estimates overlapping between these two networks.

Nirsevimab Effectiveness Against Hospitalization

[5:05:20]
Here, we see a similar table for Nusabimab effectiveness against RSV-associated hospitalization among infants during their first RSV season. Among over 600 hospitalizations in children included in the VISION analysis, 81% of RSV-positive children did not receive Nusabimab compared to 55% among RSV-negative children. Similarly, among nearly 700 hospitalizations in children included in the NVSN analysis, 89% of RSV-positive children did not receive Nusabimab compared to 61% among RSV-negative children. Among children that had received Nusabimab, the median time since dose at the time of their hospitalization was 61 days in VISION and 52 days in NVSN.

[5:06:08]
The estimated adjusted product effectiveness against RSV-associated hospitalization was 79% in VISION and 82% in NVSN, with 95% confidence intervals for both point estimates overlapping between these networks.

Nirsevimab Effectiveness Against ICU Admission

Here, we see a similar table for Nusabimab effectiveness against RSV-associated ICU admission among infants during their first RSV season, with results from VISION, NVSN, and Overcoming. Among the 374 hospitalizations in children included in the VISION analysis, 86% of RSV-positive children did not receive Nusabimab compared to 55% among RSV-negative children.

[5:07:01]
In NVSN, 92% of RSV-positive children did not receive Nusabimab compared to 56% among RSV-negative children. Similarly, among 672 children in the Overcoming analysis, 87% of RSV-positive children did not receive Nusabimab compared to 56% among RSV-negative children. The median time since dose among children that had received Nusabimab was 56, 52, and 50 days for VISION, NVSN, and Overcoming, respectively, with adjusted product effectiveness estimates of 82%, 88%, and 88% with overlapping confidence intervals between each of the networks. Next, I'll present data regarding maternal RSV vaccine effectiveness during the 24-25 RSV season in the United States.

Maternal RSV Vaccine Effectiveness Against ED Visits

[5:08:06]
Similar to the previous tables, here we see maternal RSV vaccine effectiveness against RSV-associated ED visits among infants during their first RSV season with results from VISION. I do want to highlight that on this slide and the next, there is an additional column to account for median days since the infant's birth. Among nearly 1,000 ED visits in children included in the VISION analysis, 79% of RSV-positive children did not have evidence of maternal RSV vaccine receipt compared to 65% among RSV-negative children. Among children with documentation of maternal RSV vaccine receipt, the median days since birth was 53, and the median days since maternal RSV vaccine administration was 85. Estimated maternal RSV vaccine effectiveness against RSV-associated ED visits was 54% with a confidence interval of 35 to 67%.

[5:09:12]
Moving on to maternal RSV vaccine effectiveness against RSV-associated hospitalization among infants during their first RSV season with results from VISION and MVSN.

Maternal RSV Vaccine Effectiveness Against Hospitalization

Of 256 hospitalizations among children included in the VISION analysis, 81% of RSV-positive children did not have evidence of maternal RSV vaccine receipt compared to 63% among RSV-negative children. Similarly, among the 326 hospitalizations among children included in the MVSN analysis, 82% of RSV-positive children did not have evidence of maternal RSV vaccine receipt compared to 65% among RSV-negative children. Among children with documented maternal RSV vaccine receipt, the median days since birth for VISION and MVSN was 35 and 32 days respectively.

[5:10:04]
In the median days since maternal vaccination was 73 days in VISION and 71 days in MVSN. The estimated adjusted vaccine effectiveness against RSV-associated hospitalization was 79% in VISION and 70% in MVSN with overlapping 95% confidence intervals between networks. Okay. There are some limitations to keep in mind when interpreting findings from these real world product effectiveness results.

Limitations of Real World Product Effectiveness Results

First, these systems and methodologies differ in enrollment and population. While we can generalize across studies, findings may not be directly comparable.

[5:11:04]
Second, while the study's design and analysis can help control for potential confounders like health-seeking behavior, residual confounding was possible, although a variety of sensitivity analyses were performed to assess the influence of known confounders. Third, misclassification of RSV immunization status was possible, although a variety of sources were leveraged to determine immunization status.

Conclusions and Considerations on Effectiveness

I'll end with conclusions and considerations. Here we summarize the real world product effectiveness estimates of the data just presented, seen in black, alongside the clinical trial efficacy estimates for each outcome, seen here in blue.

[5:12:00]
ED visits were not direct outcomes measured during clinical trials for either product. However, for RSV-associated hospitalization and ICU admissions, the effectiveness estimates for both nercevumab and maternal RSV vaccine are consistent with findings from clinical trials. Taken together, these real world findings during the 24-25 US RSV season suggest that both nercevumab and maternal RSV vaccination are effective at preventing RSV-associated ED visits, hospitalizations, and critical illnesses. Continued monitoring will be needed to assess additional outcomes.

Impact of RSV Prevention Products on Pediatric Hospitalizations

Now we'll discuss the impact of RSV prevention products on pediatric RSV-associated hospitalizations within the United States.

Surveillance Systems for Impact Assessment

To assess the impact, we analyzed data from two active population-based US surveillance systems that monitor laboratory-confirmed RSV-associated hospitalizations.

[5:13:07]
The first system is RSVNet, which is a component of the ResNet system and monitors RSV, influenza, and COVID-19-associated hospitalizations among patients of any age from 13 states. The second system is NBSN, which I spoke about earlier, that monitors hospitalizations among children with acute respiratory illnesses from seven US medical centers.

Ecological Analysis Method

We performed an ecologic analysis that compared RSV-associated hospitalizations and rates between RSV seasons before and after RSV prevention introduction, including pre-pandemic seasons of 2018-2019 and 2019-2020 for RSVNet and 2017-2020 for NBSN and the 24-25 season, which was the second year of product availability.

[5:14:08]
We excluded 2020 through 2023 because these seasons were impacted by the COVID-19 pandemic and also the 24-25 RSV season, which was the first year of RSV prevention product introduction during which there was low availability and uptake of products. We compared adjusted RSV-associated hospitalization and ICU admission rates for RSV seasons before and after product introduction. We looked at weekly hospitalization, okay, we compared adjusted RSV-associated hospitalization and ICU admission rates from RSV seasons before and after RSV prevention product introduction.

Comparison of Adjusted Hospitalization Rates

We looked at weekly hospitalization rates from RSVNet and monthly rates from NBSN during 24-25, comparing them with the same weeks and months in prior seasons.

[5:15:08]
We also examined cumulative hospitalization rates for 24-25 across both networks and compared them to pooled rates from prior seasons. We also analyzed cumulative ICU admission rates in RSVNet. To quantify these differences, we calculated rate ratios comparing cumulative rates between time periods. And from those, we estimated the relative rate reductions calculated as 1 minus the rate ratio multiplied by 100.

Rate Changes by Age Group

To examine changes related to RSV prevention product availability, we assessed changes in rates before and after product introduction for three age groups with different prevention product options.

[5:16:04]
First, we assessed rate changes among infants aged 0-7 months, a population that was eligible for nirsevimab, but also could have been protected by maternal RSV vaccination. Then we looked at rate changes among children aged 8-19 months, among whom a small number of children at risk for severe RSV disease would have been eligible to receive nirsevimab based on risk conditions. And lastly, we assessed rate changes for children aged 20-59 months who were ineligible for RSV prevention products. The older two groups were included as comparison populations because they were largely ineligible for RSV prevention products.

Comparison Populations

[5:17:02]
They were included to detect hospitalization rate changes that may have occurred between time periods that were unrelated to RSV prevention product uptake.

Product Availability and Coverage

During 2024-2025, RSV prevention products were available before RSV season onset in most states with product coverage that increased over time. By March of 2025, nirsevimab coverage among infants aged 0-7 months ranged from 21-48% among reporting jurisdictions. And as of January 2025, 39% of pregnant women aged 18-49 years had received RSV vaccine. I want to briefly explain the kind of analysis we used.

Explanation of Ecological Analysis

We performed an ecological analysis, which means we looked at patterns across whole groups of children over time.

[5:18:01]
In this case, we compared RSV-associated hospitalization rates across three different age groups, young infants, toddlers, and preschool-aged children across several RSV seasons to see how hospital rates changed or didn't change within each age group over time. If no new RSV prevention products have been introduced, we would expect to see the same kinds of patterns we've seen in the past where infants get hospitalized at the highest rates, followed by toddlers, and then preschool-aged children. While these rates are different for each age group, they tend to stay relatively consistent from year to year. But in the 2024-2025 season, that changed.

Expected vs. Observed Patterns

New RSV prevention products were available to help protect some children from severe RSV disease. These products weren't approved for all children.

[5:19:01]
They were recommended only for specific age groups, including infants 0-7 months who were eligible for nircevimab or were potentially protected by maternal RSV vaccine, and children 8-19 months, which only a small number would have been eligible for nircevimab based on risk conditions. Children 20-59 months were ineligible for RSV prevention products. Because of these differences, we were able to look at each age group separately and compare hospitalization rates before and after these products were introduced.

Analysis to Determine Product Impact

We used the analysis to help determine whether RSV hospitalization rates dropped more in the 2024-2025 season for the infants who were eligible for these new prevention products compared to older children who weren't eligible. We looked at how much hospitalization rates changed from the seasons when no products were available to the 2024-2025 season after products were introduced.

[5:20:01]
If we saw a bigger drop in hospitalizations among infants 0-7 months than we saw among children 8-19 and 20-59 months, that would suggest that these products had an impact in protecting the infant group at the population level.

Results from Ecological Analysis (Hospitalizations)

Now we'll move on to results from this analysis. Combined, the two networks identified more than 20,000 children less than 5 who had RSV associated hospitalizations across these two time periods. Overall, the proportions of children age less than 5 with an RSV associated hospitalization who were age 0-7 months decreased in 2024-2025 compared to seasons before prevention product introduction as shown in the bottom two blue boxes of each bar. Dropping from 51% to 29% in RSV net and from 46% to 38% in MVSN.

[5:21:04]
Additionally, the median age of hospitalization nearly doubled in both systems from 7.7 to 15.4 months in RSV net and from 6.3 to 12.7 months in MVSN. This means that in 2024-2025, the typical age of a child hospitalized with RSV is older than it was in prior seasons.

Cumulative Adjusted Hospitalization Rates by Age Group

Next, we looked at chemotube adjusted RSV hospitalization rates in 2024-2025 compared to seasons before product introduction by age group. From left to right, we will show rates for each network among infants age 0-7 months, children age 8-19 months, and children age 20-59 months. The light blue bars represent seasons before RSV prevention product introduction. And we see that chemotube RSV associated hospitalization rates among infants age 0-7 months were 17-16 among children age 8-19 months were 5.8 and 5.3. And among children age 20-59 months were 1.7 and 1.1 in RSV net and MVSN net.

[5:22:28]
Here, we added 24-25 rates represented by the purple bars.

Rate Decreases Among Younger Children

And we can see that among children age 0-7 months, rates decreased to 10.5 in RSV net and 11 in MVSN. There was no rate decreases among older children, which corresponded with a 38% and 31% reduction in hospitalization rates in 2024-2025 compared to seasons before product introduction.

[5:23:04]
In RSV net and MVSN respectively. And no reductions occurred among older children. We then looked more closely at changes in RSV associated hospitalization rates among those infants age 0-7 months by looking specifically at rates among infants age 0-2 months and age 3-7 months.

Changes in Hospitalization Rates Among Infants 0-7 Months

And we found that RSV associated hospitalization rates were reduced by nearly half among the youngest infants, those age 0-2 months with 47% reduction in RSV net and a 46% reduction in MVSN net in 24-25 compared to prior seasons.

Conclusions and Considerations on Impact

Finally, I'd like to end with conclusions and considerations related to the impact of RSV prevention products.

[5:24:06]
In summary, two population-based surveillance networks demonstrated reductions in RSV associated hospitalizations during the 24-25 season among infants eligible for RSV prevention products with 38% and 31% reductions in 24-25 compared to RSV seasons before product introduction among infants age 0-7 months. Reductions in both RSV associated hospitalization were greatest among those infants 0-2 months who were born just before or during the RSV season. This is a group at highest risk for hospitalization and underscores the importance of protecting those infants through maternal vaccination during pregnancy or nurseva mat in the first week of life as recommended by ACIP. And lastly, ongoing monitoring of RSV disease trends including severity and age distribution is crucial to assess the sustained impact of these products over time.

[5:25:12]
I want to acknowledge all of our CDC colleagues as well as all the contributors that provided data to this presentation. Thank you.
[Dr. Martin Kulldorff]
Thank you for that, Dr. McNeil.

Questions on Effectiveness and Impact

I want to point out that the vote that we're scheduled to have on the RSV product is for cholesterol, PMAB, and not on these two. So, in the interest of time, we might just try to move forward. But if there are questions from any members of the committee, then please.
[Dr. Rezif Levy]
Yes. So, first, thank you for this detailed analysis.

Question on Refinement of Outcomes and Sub-Analyses

Quite a lot of very useful information. I guess that my question about maybe some complementary analysis that will be good to have is a little bit of more refinement of the outcomes that are being measured in various dimensions.

[5:26:08]
So, the first dimension is to understand in a more nuanced way in terms of what babies are benefiting from this the most. Specifically, preterm babies, babies with comorbidities compared to maybe healthy term babies, to see if there is any difference in the benefit of these products. I also think that it will be useful to consider overall all-cause lower respiratory tract infections, because one thing that we would like to make sure that what we see here is not partially an artifact that these babies tend just to be tested negative, more likely to be tested negative to RSV, but nevertheless still suffer from severe LRTIs.

[5:27:01]
In fact, I would even suggest to look on overall respiratory infections, because at the end of the day, we would like to make sure that we impacted all the severe cases. And maybe the last dimension I would like to see maybe more information is, you know, hospitalization is definitely a bad outcome for babies, for everybody, but not all hospitalizations are made the same. So, some hospitalizations are longer. Some of them require very intense care. So, I think that trying to refine the analysis to also consider the number of hospital days, what types of care was provided in different fractions of those days would be very complementary to understand the overall benefits in a more, maybe more nuanced way. Thank you.

Response on Preventing Respiratory Infections and Statistical Power

[Ben Spader]
Yeah, thanks. I'll respond quickly, and I don't know if because of time, we want to also go to SMEs who can speak in more depth, but I think, you know, maybe just a couple of quick comments.

[5:28:03]
So, one, certainly in terms of preventing respiratory infections, I mean, we all agree completely, right?

Question on Combining Clinical and Ecological Trials

It's not just RSV. It is as much as we can prevent infant pediatric hospitalizations would be strongly valued. I would note that RSV certainly provide, is the cause of a very large proportion of hospitalizations, particularly among newborns. So, even with RSV products, it by itself is having a large public health impact. I think to some of the other ideas you raised about sub-analyses, I absolutely think there would be value in terms of having more granular analyses. I suspect the one limitation, if we have time, if we want to go to SMEs on this, would be just the statistical power we have to be able to dig into further analyses.

[5:29:08]
Dr. Hillman?

Question on Interaction with COVID Vaccines

[Dr. Joseph Hiblin]
Excellent presentation, combining small number, small N clinical trials with large-scale ecological trials, which is always a challenge. It would appear to me that these come to similar magnitude of effect sizes in the clinical trials and in the ecological trials. Is that correct?
[Ben Spader]
Similar, yes. I think we also have to remember that the clinical trials were not done within the United States. Obviously, there are differences, but I think the overall magnitude, I think the big picture is, yes, we are. I would say we are seeing the real-world impact that we would expect based on the clinical trials. Second is that the big event that happened between the two ecological studies, of course, was COVID.
[Dr. Joseph Hiblin]

[5:30:02]
Do you think you have any evidence of an interaction or a protective effect of COVID vaccines on RSV hospitalizations or phenomenon?
[Ben Spader]
There would certainly not be, biologically, there would not be a direct effect of COVID-19 in any way on RSV because they are very different viruses. Thank you. Dr. Malone?

Question on Monoclonals and Viral Drift

[Dr. Robert Malone]
Thanks. Sorry, a little more virology. We have two monoclonals. Monoclonals are notoriously susceptible to viral drift. I could imagine an argument made that it would be useful if particularly those two monoclonals were towards different epitopes. Do we have that information?

Response on Monoclonals and Binding Sites

[Ben Spader]
Yes, and that is part of the game.

[5:31:00]
We'll actually cover it in a later presentation, is that by having two different monoclonal, they both target the larger pre-fusion protein. But yes, there's a possibility that if resistance were to occur to one of the monoclonals, the other one would remain productive. So that's part of the thinking that went into the workgroup and their deliberation around having a second monoclonal.
[Dr. Robert Malone]
Yeah, I support that.

Question on Monitoring for Drift and Selective Pressure

This also raises the issue because clearly you've demonstrated there is very significant viral pressure, infectious pressure. Is there a monitoring for drift?

Response on Selective Pressure and Genomic Monitoring

[Ben Spader]
So I think one important thing to remember is that RSV infects all people multiple times throughout their life. So there's ongoing circulation. So we don't think that infecting or providing protection to a small population actually creates a large population-based selective pressure.

[5:32:09]
So we do some genomic monitoring for RSV, but there is not expected to be the ecologic selective pressure because everybody else is still transmitting the virus, right? So the general population is basically a sink that's maintaining the genomics. Correct, yep.

Question on Drug-Drug Interactions and Simultaneous Vaccination

[Dr. Robert Malone]
So another point, because it's going to be a issue with the ACIP going forward to ask the question about drug-drug interactions, I infer that some fraction of those receiving these products are fully vaccinated at birth under the standard schedule. And some fraction may not be.

[5:33:00]
If that's the case, then capturing those data, demonstrating that there presumably is no difference in safety signal or effectiveness between those populations that concurrently receive standard vaccination protocol and those that don't seems to be something that would be useful if you're not doing that yet.

Response on Simultaneous Vaccination and Clinical Trials

[Ben Spader]
Yeah, and I think I would look to my safety, my colleague from safety if she would like to comment further. I think obviously the other aspect of this is these products came through different clinical trials. So there was not, you know, an ability to look across impact between clinical trials, obviously.
[Dr. Robert Malone]
But with the data you're capturing right now, you have an opportunity to do that as field effectiveness.
[Dimitri Daskalakis]
Yeah, looking at Demetri, are there comments online? Yeah, we're just flagging that there's a hand in the room.
[Dr. Martin Kulldorff]

[5:34:03]
We have somebody remotely, BB.
[Dr. Sandra Fryhofer]
Oh, yeah, sorry.

SME Response on Binding Sites and Genetic Surveillance

This is the SME room. Yeah, so there were a couple of questions. One was about the binding sites with the two different monoclonals. These two different monoclonals do indeed bind to different locations in the virus. And you're correct that some viruses do drift away from monoclonal antibodies. These probably aren't quite as prone to drifting just because of the way the evolution happens in this virus. However, we agree and are doing genetic surveillance to ensure that the effectiveness is maintained.
[Dr. Rezif Levy]
Thank you, Dr. Devine.

Question on Efficacy Changes Over Time and Negative Efficacy

Yeah, so just to build on the last point. One of the things that I think is also important to monitor is how the efficacy changes over time, even within a season. At least, if I'm not mistaken, when I interpreted the results from the maternal vaccine, when you look on day 180 to 360, you see something that looks like a negative efficacy, where there are more hospitalization cases among the vaccinated versus the one that were not.

[5:35:19]
Again, I think that what I understand about the RSV attempts to protect against RSV, it's a tricky virus that, more often than not, fools interventions in unexpected ways. So I think we need to be extra careful to understand what is our understanding, the explanation or potential explanations to what we see.

Response on Waning Effectiveness and Protecting Vulnerable Infants

[Ben Spader]
Yeah, I mean, certainly, you know, we know that effectiveness of these products wanes over time. And so it does, it's going to create its own impacts of, you know, you're protecting the youngest children. And then part of what we want to do, right, is to protect them when they're most vulnerable so they get to the point that they are, have fully developed immune systems in which they, like healthy adults, generally are infected with, or I should say healthy teenagers, for example, are infected but do not have severe RSV disease.

[5:36:23]
So really, like, I mean, the biggest impact among the new movers is getting those zero to two months and getting them through that most vulnerable period.
[Dr. Martin Kulldorff]
We have another online, I think it's initial BB again.

SME Response on Monitoring Duration of Protection

[Dr. Christine Hahn]
Yes. Hi, this is Dr. Meredith Amaro. I'm also with Corvid at CDC and just wanted to respond to the question about monitoring up to 150 days or beyond. Right now, our, the challenge of the way in which we administer these products is that we do at the beginning of the season and as we build up coverage, you know, the season progresses.

[5:37:08]
And so you'll see from the average time between vaccination and hospital, or immunization and hospitalization for the two analyses, that we aren't getting to very many children that have, have received these immunizations out to 120 to 180 days. And that's part of that is because of the way that we seasonally introduce these products. I think we are hoping that other places where RSV circulation is less seasonal, perhaps more year round will help us to answer some of these questions about the duration of protection. But right now, it is a bit of a challenge in terms of looking at the tails of protection in our current surveillance systems.
[Dr. Martin Kulldorff]
Thank you for excellent discussion suggestions here.

Acknowledgment of Discussion

[Dr. Cody Meissner]

[5:38:00]
Can I make a comment?

Comment from Dr. Cody Meissner on Accomplishment of RSV Prevention Products

I'm sorry. Please go ahead. This is Cody. Yep. As someone who's been on the RSV work group and as a pediatrician, I mean, people need to understand what a spectacular accomplishment these results are. As was pointed out, RSV is the most common diagnosis among children who are hospitalized in the first 12 months of life. And two to three percent of all children, that includes term as well as increased risk children with heart disease or lung disease, they have a higher rate, but are hospitalized. And this is an astonishing accomplishment that's really developed because of an increased understanding of the fusion proteins that exist in at least two different configurations, a pre and a post configuration, against which the monoclonal antibody has been made for the pre-fusion.

[5:39:15]
So this is a spectacular accomplishment. It's something that the CDC does very well in providing this sort of data so that recommendations can be made. And I just want to recognize the contribution of Jefferson Jones and Pablo Sanchez on the work group for working so diligently to get this passed and through, finished, and get the recommendations that we now have. But people should understand that this is a truly spectacular accomplishment and will have an enormous impact on public health.
[Dr. Martin Kulldorff]

[5:40:08]
Thank you for those positive words, Dr. Meissner.

Continuation of Roll Call

Before we go to the next presentation, we have a little bit more of a roll call, I believe, because there were some people who were not able to be heard.
[Dr. Mina Zadeh]
Sure. We had some of our liaisons who were unable to unmute. So if you would like to go ahead and unmute and introduce yourselves, that would be great.
[Dr. Cody Meissner]
Go first.

American College of Physicians Introduction

Jason Goldman. Clinical Affiliate Professor of General Internal Medicine at Florida Atlantic University. President of the American College of Physicians, representing 160,000 internal medicine specialists to over 145 countries, as well as being a primary care physician in general practice expertise in taking care of patients in the office and in the clinic.

[5:41:07]
Thank you.
[Dr. Mina Zadeh]
Thank you for that.
[Dr. Vicki Pepsworth]
Hello, Masoud.

American Osteopathic Association Introduction

Sorry, Masoud Mahmoudi, American Osteopathic Association.
[Dimitri Daskalakis]
Sorry, Masoud Mahmoudi, American Osteopathic Association. I don't know if you could hear me.
[Dr. Mina Zadeh]
Thank you. Anybody else? Thank you.

Conclusion of Roll Call

[Dr. Martin Kulldorff]
Thank you so much for that. And it's a pleasure to have you with us on this meeting. So we will now move on to the next presentation on the safety of these products by Drs. Silva and Daly.

Safety of RSV Products Presentation

[Dr. De Silva]
Good afternoon.

Prenatal RSV Pre-F Vaccine Safety (Dr. De Silva)

Can you hear me?

[5:42:00]
Yes, we can hear you. Okay. I am an internal medicine and pediatrics physician and a senior research investigator at Health Partners Institute in Minnesota, which is one of the vaccine safety data link sites. Today, I'll be presenting results for prenatal RSV pre-F vaccine safety during the 2023-2024 respiratory season from the vaccine safety data link. Next slide, please.

Vaccine Safety Data Link (VSD) Overview

Established in 1990, the vaccine safety data link, or VSD, is a collaborative project between the CDC's Immunization Safety Office and integrated healthcare organizations in the United States. The VSD monitors the safety of vaccines used in the U.S., primarily through observational multi-site studies using real-world data. The project includes data on approximately 15.5 million individuals across all sites annually, which represents approximately 4.5% of the U.S. population. The VSD has an annual birth cohort of approximately 115,000 live births.

[5:43:01]
Data is organized using a common data model with standardized coding systems. The map on the right shows currently participating VSD healthcare organizations. There are 13 VSD sites that provide clinical, methodological, and data expertise. 11 of the 13 sites provide data for the project. Sites that do not provide data are denoted with an asterisk. Next slide, please. The prenatal RSV vaccine was recommended for use by ACIP in September of 2023 for use between 32 through 36 weeks gestation with seasonal administration from September through January.

Prenatal RSV Vaccine Recommendation and Clinical Trial Findings

The phase 3 RSV pre-F clinical trial identified non-significant imbalances among vaccinated women compared to placebo recipients in preterm birth and gestational hypertension and pre-eclampsia. Next slide, please. Prenatal RSV pre-F vaccine safety outcomes we evaluated in this study are acute outcomes occurring within 42 days of vaccination, preterm birth, small for gestational age at birth, stillbirth, and hypertensive disorders of pregnancy, which we evaluated as a combined outcome, as well as the individual outcomes of gestational hypertension, pre-eclampsia, eclampsia, and HELP syndrome.

Safety Outcomes Evaluated

[5:44:18]
Next slide, please. We used a target trial emulation design to compare vaccinated and unvaccinated persons at each gestational week.

Target Trial Emulation Design

This study design attempts to recreate a randomized experiment from observational data. For the eligibility criteria, we included pregnant women 16 through 49 years of age with gestational age 32 through less than 37 weeks during September 22nd, 2023 through either January 31st, 2024 or February 29th, 2024 for two sites that continued vaccinating through February. The treatments we compared were RSV pre-F vaccination during pregnancy to no RSV pre-F vaccination during pregnancy.

[5:45:00]
Pregnant persons exposed to RSV pre-F vaccine were matched one-to-one on VSD site and propensity to be vaccinated to unvaccinated pregnant persons during the same gestational week. All participants were followed for outcomes from the index date through two weeks after the pregnancy end date. Unvaccinated matches were assigned an index date equal to the gestational day of vaccine for their vaccinated match. The match pair was censored if the unvaccinated person was later vaccinated. Next slide, please.

Risk Ratio Estimation

We…back one. Next slide. We estimated risk ratios with 95% confidence intervals using a log binomial model with robust variants with adjustment for nulliparity for the pregnancy and infant outcomes. For small for gestational age at birth, match sets were excluded if the infant weight was not available for either infant in the match pair. For hypertensive disorders of pregnancy, the match set was excluded if disease onset was before or on the index day for either included pregnant woman.

[5:46:06]
Next slide, please. This slide…

Balance Plot of Covariates

This slide shows a balance plot of covariates included in the propensity score before and after matching. In the figure, the x-axis shows the standardized mean difference, or SMD, and the y-axis shows the covariate included in the propensity score. Blue circles are the standardized mean differences for the entire population before matching. Red circles show the standardized mean difference after matching. This includes only the match pairs. Unmatched persons are excluded. The balance plot shows that characteristics of the included pregnant women are similar after matching. Next slide. This table shows the age group, race, ethnicity, receipt of one or more other vaccines during pregnancy, and nulliparity of the matched cohort.

Characteristics of Matched Cohort

There are 13,966 matched pairs included in this analysis. Of note, the matched cohort is not unique in vigils, as some initial unvaccinated persons were ultimately vaccinated and subsequently rematched as vaccinated.

[5:47:08]
While the characteristics are similar, RSV-vaccinated women tended to be older than their unvaccinated matches. The vaccinated group had a higher percentage of Asian patients and lower percentage of Black and Hispanic patients compared to their unvaccinated matches. 98.5% of the vaccinated group had received at least one other vaccine during pregnancy compared with 81% of the RSV-unvaccinated group. There was a higher percentage of nulliparous women in the RSV-vaccinated group compared with the unvaccinated group. Next slide, please. This slide and the next show results for the risk of acute outcomes among pregnant women receiving RSV-pre-F vaccine and their unvaccinated matches.

Risk of Acute Outcomes (1-6 and 1-21 Days)

The table lists the outcome, the risk intervals evaluated, either 1 through 6 days or 1 through 21 days on this slide, the number of events and events per 10,000 persons, and the risk ratio with 95% confidence intervals.

[5:48:01]
If an outcome we evaluated is not included in this figure, it is because there were no events in either group for these outcomes. There were no significant differences between the RSV-vaccinated group and their unvaccinated matches. Next slide.

Risk of Acute Outcomes (1-42 Days)

This slide shows results for the 1 through 42-day risk interval for acute safety outcomes among pregnant women receiving RSV-pre-F vaccine and their unvaccinated matches. Again, the table lists the outcome, the number of events and events per 10,000 persons, and the risk ratio with 95% confidence intervals. Again, if an outcome we evaluated is not included in this figure, it is because there were no events in either group. There were no significant differences between groups for these outcomes. Next slide, please.

Risk of Preterm Birth

The next few slides show similar tables. Each slide focuses on a specific outcome. Each table shows the number of matched pairs included, the number of events for both the RSV-vaccinated and unvaccinated women, and the adjusted risk ratio.

[5:49:01]
This slide shows preterm birth risk among pregnant women receiving RSV-pre-F vaccine and unvaccinated matches. The adjusted risk ratio for preterm birth is 0.90 with confidence interval including 1. There is no association between RSV-pre-F vaccination and preterm birth risk. Next slide, please.

Risk of Small for Gestational Age at Birth

This slide shows small for gestational age at birth risk among infants born to RSV-pre-F vaccinated women or their unvaccinated matches. There is no association between RSV-pre-F vaccination and small for gestational age at birth risk. Next slide, please. This slide shows the stillbirth risk in RSV-vaccinated pregnant women or their unvaccinated pregnant matches.

Risk of Stillbirth

Again, there is no association between RSV-pre-F vaccine and stillbirth risk. Next slide, please.

Risk for Hypertensive Disorders of Pregnancy

This slide shows the risk for hypertensive disorders of pregnancy among pregnant women receiving RSV-pre-F vaccine and their unvaccinated matches.

[5:50:03]
The adjusted risk ratio for any hypertensive disorder of pregnancy is 1.09 with confidence interval 1.03 to 1.15. The adjusted risk ratios for the individual hypertensive disorders of pregnancy were statistically significant for preeclampsia and gestational hypertension. There is an association between the RSV-pre-F vaccine and any hypertensive disorder of pregnancy, preeclampsia, and gestational hypertension. Next slide, please.

Severity of Hypertensive Disorders of Pregnancy

Only individuals with a diagnosed hypertensive disorder of pregnancy are included on this slide. This slide evaluates the rates of cesarean delivery, hypertensive disorder of pregnancy admissions following the birth hospitalization, and lengths that stay longer than three days for the birth hospitalization for both the infant and mother stratified by the type of delivery and shown by RSV vaccination status.

[5:51:00]
There are 2,344 RSV-pre-F vaccinated women and 2,056 unvaccinated women included. The columns show the severity indicator and the number and percent of each group who had that severity indicator. There are similar rates of cesarean delivery and hypertensive disorder of pregnancy admissions following the birth hospitalization in both groups. The percent with the length of stay over three days was slightly higher in the RSV-pre-F group compared with the unvaccinated group, except for infants following cesarean delivery. These results suggest similar severity for hypertensive disorders of pregnancy in both the vaccinated and unvaccinated groups. Next slide, please.

Serious Adverse Events in Phase Three Trial

This slide shows results for serious adverse events in the phase three clinical trial of the RSV-pre-F vaccine-administered pregnant persons. There are more cases of gestational hypertension and preeclampsia among RSV-pre-F vaccine recipients than among placebo recipients, although these associations were not statistically significant.

[5:52:04]
Next slide. Similarly, the results of a retrospective observational cohort study of patients who delivered at 32 and 07 weeks gestation or later at two New York City hospitals from September 22nd, 2023 to January 31st, 2024, found a significant association between the RSV-pre-F vaccine and hypertensive disorders of pregnancy in a time-dependent coxical variant regression model.

Retrospective Observational Cohort Study Findings

This association was not significant in an unadjusted or adjusted multivariable logistic regression model. In stratified analyses by site and insurance status, the association between hypertensive disorders of pregnancy and RSV remained among those with private insurance and at one of the two included sites. Next slide, please.

Conclusion of Prenatal RSV Vaccine Safety

In conclusion, RSV-pre-F vaccine is not associated with increased risk for acute safety outcomes, preterm birth, small for gestational age at birth, or stillbirth.

[5:53:02]
RSV-pre-F vaccine is associated with a small but statistically increased risk for hypertensive disorders of pregnancy. These findings are consistent with those of the phase three trial and a large observational study. This finding is limited by potential residual confounding or outcome misclassification. Importantly, the severity of hypertensive disorders of pregnancy was similar between those that received the RSV-pre-F vaccine and their unvaccinated matches based on rates of cesarean delivery, admissions following birth hospitalization, and length of stay. Results of the 2024-25 season analysis are pending and will be important for further understanding of prenatal RSV vaccine safety. Next slide. Thank you for your time.

Acknowledgment

I look forward to answering any questions you may have.

Safety of Nirsevimab in Infants (Dr. Matt Daly)

[Dr. Martin Kulldorff]
Thank you for that. And I think before questions, I think we should continue with a presentation by Dr. Matt Daly, which is also about safety.
[Eric Weintraub]

[5:54:05]
Thank you. Can you hear me?
[Dr. Martin Kulldorff]
Yes.
[Eric Weintraub]
Great. So, I'm Matt Daly. I'm going to be presenting on monitoring the safety of nircivumab in infants birth through less than eight months of age. These are preliminary results from the vaccine safety data link for the 2024-2025 season. Next slide. I have no conflicts of interest. I'm presenting on behalf of the vaccine safety data link. Next slide. Next slide.

Nirsevimab Overview

To provide a little bit of nircivumab overview, as we've heard, it's a long-acting monoclonal antibody for the prevention of RSV disease. It's recommended for infants birth through less than eight months of age if no RSV vaccine was given during pregnancy. It's also recommended for select high-risk infants age eight through 19 months of age.

[5:55:01]
It has demonstrated high efficacy in phase three clinical trial and high effectiveness post-licensure, which we heard today. There was a severe shortage of nircivumab during the 2023-2024 season. Despite that, uptake has been quite high within the VSD during the 2023-2024 season. Seventy-two percent received either nircivumab or vaccine during pregnancy. Next slide. In terms of the safety database for nircivumab, it's primarily derived from three randomized clinical trials.

Safety Database from Clinical Trials

These clinical trials included healthy infants as well as more high-risk infants, and there were 3,184 who received nircivumab. Again, this is combining results across three trials. 1,284 who received placebo, the reason being that there was a two-to-one randomization of nircivumab to placebo. And then 304 who received palivizumab, which is another monoclonal antibody targeted at RSV.

[5:56:05]
Adverse events were generally balanced among infants who received nircivumab versus the comparator.

Importance of Post-Licensure Safety Data

There were some adverse events of special interest. Seven nircivumab-exposed infants had rashes that were primarily papular or maculopapular. Importantly, there were no cases of anaphylaxis, no serious hypersensitivity-type reactions reported, and no immune-complex diseases reported. Next slide, please. In the context of the safety data from the clinical trials, it is still important to perform additional post-licensure safety data, including an assessment of rare adverse events, and then also when nircivumab is given during routine care in a general patient population. So, the objective of our study was to investigate the safety of nircivumab by examining pre-specified adverse events among nircivumab recipients in the Vaccine Safety Datalink.

Study Objective

I would note that nircivumab is a passive immunization, yet the CDC and ACIP requested that the VSD evaluate its safety.

[5:57:06]
Next slide, please. The Vaccine Safety Datalink we've heard about a couple times today.

Vaccine Safety Datalink (VSD) Characteristics

I'll just highlight a couple points here. It's observational. It uses EHR data. The cohort size, as Dr. De Silva said, has an annual birth cohort of 115,000. It has the following data characteristics. We use electronic health record data, but we also have access to claims and immunization information system data, and then diagnosis codes, vaccines, and medications. These data come from inpatient, emergency department, and outpatient settings. One additional characteristic of the VSD that distinguishes us from some of the other vaccine safety systems is the ability to rapidly perform manual medical record review. While diagnosis codes have a high degree of accuracy, they're not 100% accurate. There can, for example, be a diagnosis code for seizure, and then on manual medical record review, that was found to be a ruled out seizure.

[5:58:04]
It was something else. Or in the case of an adult who has a diagnosis code for Guillain-Barré syndrome on review of the medical record, at times that could have been Guillain-Barré syndrome two years ago, which is not relevant to the vaccine given today, at least in the context of safety. And then I would also say that VSD applies a range of analytic methods to address confounding, including self-control designs. Next slide, please. This figure shows VSD sites in 2025.

VSD Sites

Next slide.

Safety Evaluation in 2023-2024 Season

We also evaluated the safety of nircivumab in the VSD during the 2023-2024 season. These results have been shared previously with the ACIP RSV work group. In that study, 36,719 received nircivumab. We had pre-specified adverse events that were monitored through a self-controlled risk interval analysis, and then all analyses were stratified by age group.

[5:59:08]
In this first season of nircivumab use, there was no elevated risk of seizures, ITP, drug reactions, fever, or sepsis. And then there were also no cases of anaphylaxis. There were cases of non-anaphylactic allergic reactions that were primarily urticaria or hives, often on the same day as nircivumab. This is not an unexpected finding given the finding of rashes from the nircivumab clinical trial.

Methods Overview for 2024-2025 Season

Next slide, please. Next slide, please. So, to provide a methods overview, and again, now I'm going to be summarizing the safety results for nircivumab for the 2024-2025 season. We used all VSD data contributing sites. The population was all infants, zero days through less than eight months of life who received nircivumab between October 1st of 2024 and February 1st of 2025.

[6:00:05]
With respect to same-day vaccines, this study included all nircivumab-exposed infants, regardless of whether they received vaccines on the same day as nircivumab. We also required health insurance enrollment through the control window. What I mean by this is that the infants needed to have health insurance with their VSD site through the end of their control window so that we could assess both the receipt of nircivumab and then whether they had adverse events through the control window. We primarily used a self-controlled risk interval design, and then we excluded infants born to someone who received RSV vaccine during pregnancy. Next slide, please.

Use of Self-Controlled Designs

I did want to provide a little bit more information about the use of self-controlled designs in safety studies. The self-controlled risk interval is a form of self-controlled case series. Self-controlled case series designs are commonly used in vaccine safety studies. The rationale for using self-controlled designs is as follows.

[6:01:01]
The exposed to a vaccine, or in this case to nircivumab, often differ in important characteristics from the unexposed, and these characteristics may not be measured in electronic health record data and can confound safety assessments.

Rationale for Self-Controlled Designs

To provide an example, if there is a new vaccine and early adopters of that new vaccine are quite healthy, then if we compared them to the unvaccinated, it would bias towards not seeing a safety finding if there was a safety finding there because of the difference between the vaccinated and the unvaccinated. Self-controlled designs are within individual designs. They control for measured and unmeasured confounders that do not vary over time, for example, a prevalent chronic condition. So, in self-controlled designs, there is an exposure, in this case nircivumab, and then we look in a risk window immediately following nircivumab or vaccine exposure compared to a later time in that same individual. So, with respect to a prevalent condition, if there's an adult who has type 1 diabetes and then receives a vaccine and then has a risk in a control window, they have type 1 diabetes in their risk window and in their control window.

[6:02:06]
That is controlled for implicitly with a self-controlled design. Next slide, please. I also want to discuss age effects because this is an important consideration in how we designed this study.

Age Effects and Separate Analyses

Diagnoses in the first month of life are often related to pregnancy, delivery, newborn-specific conditions. Healthcare utilization is different in the first month of life, and then there can be lags in health insurance enrollment. And then one other consideration, with the exception of the birth dose of hepatitis B vaccine, the earliest that all other vaccines recommended can be given is 38 days of age. So, for all of these reasons, we performed separate safety analyses for the newborns, which here we're defining as 0 days through 37 days of age, and then infants out of the newborn period, which here we're defining as 38 days through 8 months of age. Next slide, please.

Adverse Events Monitored

[6:03:00]
In terms of the adverse events that we monitored, the adverse events were pre-specified, and they were chosen based on biologic plausibility, clinical trial data, as well as expert opinion, including feedback that we received from the ACIP RSV workgroup. The adverse events were primarily identified based on ICD-10 diagnosis codes. We also used platelet counts for one of the outcomes. Next slide, please. Here are the outcomes for the nircivumab safety surveillance study. The first column shows the adverse event. The next column shows the study design. We examined seizures, immunothrombocytopenia, or ITP, drug reaction, fever, and sepsis.

Study Design for Adverse Events

These were self-controlled risk interval designs. And then anaphylaxis and non-anaphylactic serious allergic reactions, in which the counts were monitored, and then also have plans to study autoimmune and immune complex disease. However, those type of outcomes in newborns and infants are rare and may have a long latency, and so the plan is to examine these as a case control study at the end of surveillance.

[6:04:06]
Next slide, please.

Risk and Control Windows

So let me walk you through this slide. Here are the risk and control windows for each of the adverse events in the self-controlled risk interval. The first column is the adverse event. I would highlight that each row is a separate analysis, as I explained, and then age at nircivumab administration, and then risk window in days, and this refers to days after receipt of nircivumab, and then a control window, and then the setting in which we identified these cases. Next slide.

Exposure-Dependent Events

There are also conditions that we call exposure-dependent events, including anaphylaxis and non-anaphylactic allergic reaction. One way to think about this is that there's not essentially a baseline rate of anaphylaxis. You need an exposure to something, such as a medication or a bee sting or a peanut product. So for these, we monitor cases in a risk window and then manually review those cases.

[6:05:00]
So in the case of anaphylaxis, the risk window was 0 to 2 days after nircivumab administration, and then in the case of non-anaphylactic allergic reactions, we looked 0 through 7 days. Next slide, please.

Additional Information on Outcomes

This provides some additional information about the outcomes that we used for the nircivumab safety surveillance study. The first column is the adverse event. The next column is the ICD-10 codes that we used, and then the last column provides some additional information. So I'd just highlight that for immune thrombocytopenia, or ITP, we required both ICD-10 codes and platelets less than 50,000. Next slide, please.

Analytic Methods (SCRI)

This slide has some additional information about our analytic methods. This is the last methods slide. Again, this is for the self-controlled risk interval analysis, or SCRI. For each pre-specified outcome, we identified cases that occurred within either the risk or the control window. There were two observations per individual, one per control window and one per risk window, and then informative cases have an outcome in one window but not the other, and then the cohort must have at least one outcome in each window to estimate an effect, and then our models, as I explained before, were stratified by age group.

[6:06:14]
Next slide.

Results for 2024-2025 Season

Next, we'll review results, and again, as I would highlight, these are from the 24-25 season, so we identified 117,427 children, this is neonates and infants, zero days old through less than eight months of age. We then applied our enrollment criteria, 43,532 received nircivimab, we excluded 1,663 who also received RSV vaccine during pregnancy. This does not necessarily represent an administration error because there are some specific circumstances when an infant who was exposed to RSV vaccine during pregnancy would still be eligible for nircivimab, and then we stratified by age.

[6:07:00]
There were some kids who, when we established this cohort, had received nircivimab at the very end of last season, the 23-24 season, and so were included in that safety analysis, so those also were excluded. So, from this study flow, we had 9,855 neonates zero to 37 days of age exposed to nircivimab who contributed to the safety analysis, and then 28,054 infants in the 38 days to less than eight months of age at the time of nircivimab administration who contributed to the safety analysis. Next slide, please.

Nirsevimab Administration Patterns

I'm going to provide a couple figures that provide context for the safety results that follow in this graph. We're looking at number of doses on the y-axis and then age in weeks on nircivimab administration date on the x-axis, and as you can see, the administration patterns were quite heterogeneous, and by that I mean any given week of age up until eight months, infants

[6:08:00]
could have been exposed to nircivimab, but there is clustering of nircivimab in that first week of life, and then at two weeks, which corresponds to a two-week well-child check, and then at two months, four months, and six months of age. Next slide. This slide is focused just on the neonate cohort, days zero through 37 days of age, and then we also show here whether or not hepatitis B vaccine was given on the same day as nircivimab.

Neonate Cohort and Same-Day Vaccines

So, as you can see, for those babies who received nircivimab on day zero, their birthday, they most often received it on the same day as hep B vaccine. For those babies who received nircivimab on day one, most received nircivimab alone, although there were some who also received hep B on the same day, and then after that, for the most part, nircivimab was given not on the same day as hepatitis B vaccine. Next slide.

Simultaneous or Same-Day Receipt of Vaccines

[6:09:01]
A little more information about simultaneous or same-day receipt of vaccines. To summarize, among the neonates, the zero to 37-day-olds who received nircivimab, 20 received nircivimab on the same day as hepatitis B vaccine. And then among the infants, 38 days through less than eight months of age who received nircivimab, 84% received on the same day as vaccines. The most common combination was nircivimab plus hepatitis B, rotavirus, DTP, Hib, pneumococcal, and polio vaccines. Next slide.

Safety Results (Seizures, ITP, Drug Reactions, Sepsis, Fever)

This is the first of the safety results slides, so I'm going to walk you through it one by one, and then the format for some subsequent slides is similar. First column is the adverse event. The next column is the age group. I'll highlight again that each row represents a separate safety analysis. And then the N, the risk window, the control window, the number of cases in the risk window, the number of cases in the control window, and then the relative risk. There was no significant increase of seizures in the 24-25 season.

[6:10:01]
There also was no significant increase in seizures in the 23-24 season. However, because there was a numeric imbalance here, we performed a rapid medical record review, and what I can summarize from that is several of these cases were not seizures, but were diagnosed with something else, and seizures were ruled out. There were also several cases of a known genetic cause for seizure, and a seizure in a child who had a preexisting epilepsy. So, just to summarize, no significant increased risk of seizures in 23-24 or 24-25, and upon medical record review, some of these were not cases. Others were a known genetic seizure disorder. Next slide, please.

ITP Results

With respect to ITP, there was a single case in the risk window in that older age group. Otherwise, no cases. Next slide, please. With respect to drug reactions, there were zero cases in the risk window.

Drug Reaction Results

[6:11:01]
Zero cases in the control window, both for the younger age group and for the older age group. Next slide, please. With respect to sepsis and fever, walking through by column, this is just in the 0-37 days risk window control window, there were four cases in the risk window, nine in the control window for a relative risk of 0.44. This was only examined for the newborn cohort.

Sepsis and Fever Results

It wasn't examined for the other children because, as any parent would tell you, a one-week-old is very different from a six-month-old, and that also includes fever in a well-appearing six-month-old, which does not necessitate a workup for serious bacterial illness, which is quite rare at that age, versus fever in a newborn. In addition, we did perform additional exploratory analysis to assess whether nircivumab, again, just in this age group, could cause fever, which then led to a sepsis workup, such as blood culture, spinal fluid culture, or both.

[6:12:01]
There was a numerical imbalance detected in cultures in risk versus control windows, so we did a manual medical record review of a sample of these charts, and those charts showed no consistent pattern of concern. Those neonates typically had reasons other than fever for cultures being done. So, just to summarize, no increased risk of sepsis and fever, which was our primary analysis. Next slide, please.

Exposure-Dependent Events (Anaphylaxis, Allergic Reactions)

In terms of these exposure-dependent events, as I've mentioned, something like anaphylaxis, you need an exposure, so we just look in the risk window. For anaphylaxis, zero to 37 days, zero cases in that older age group, no cases. Other non-anaphylactic serious allergic reactions, there were 14 cases in the youngest age group, and then four in that older age group. These were primarily diagnosis codes for urticaria, or high, that occurred on the same day as nircivumab. Next slide, please.

[6:13:01]
Next slide, please.

Summary of Nirsevimab Safety

So, to provide a summary, among a population of 74,000 infants and neonates, and this is combining results across two seasons of neonates and infants exposed to nircivumab, there was no increased risk of seizures, ITP, drug reaction, fever, and sepsis, there were no cases of anaphylaxis, there were a small number of cases of non-anaphylactic allergic reactions in both years, and those were primarily coded as urticaria or hives, but without a more serious hypersensitivity reaction in those same children. So, this really should provide some reassuring data regarding the safety profile of nircivumab when used in routine clinical practice. Additional data extraction is needed for late-season nircivumab use, and so we should view these results as preliminary. Next slide. And then our nircivumab safety surveillance continues.

Continued Nirsevimab Safety Surveillance

[6:14:03]
We had three planned assessments after the 23-24 season, which, again, results were shared with the ACIP RSV workgroup, the preliminary assessment of the 24-25 season, which is what I'm presenting here today, and then an end-of-surveillance assessment, which will be cumulative with data extraction through July of 2025. We will manually review any records of anaphylaxis cases and then any other outcomes of concern. And then we had planned a case-control study of autoimmune and immune complex disease. However, it appears that there are too few cases to study in this group of outcomes at present, and just to provide a little bit more information about that, these are conditions such as myocarditis, pericarditis, arteritis, lupus, diabetes mellitus, glomerulonephritis, hemolytic anemia. There were only two cases in 24-25. Those appeared to be isoimmunization, which is basically what happens when maternal blood type is different from infant blood type, and that is what's causing hemolysis.

[6:15:05]
So, of course, that couldn't be nircivumab-associated because that happened prior to the time of nircivumab receipt. So, essentially, no cases of autoimmune or immune complex disease for the 24-25 season. So, we can't perform a case-control without any cases, but that should provide reassuring results regarding the risk of autoimmune and immune complex disease. Next slide. I'd be happy to take any questions.

Acknowledgment

Thank you very much.

Acknowledgment of Presentations

[Dr. Martin Kulldorff]
Thank you, Dr. Daly. These two presentations, these very thorough presentations illustrates how important CDC's vaccine safety data link is to monitor the safety of these products.

Public Comment Announcement

We will have questions, but there is one agenda item that we cannot move, and that is the public comment. So, we will do the public comments at 4.15, and that is in 10 minutes.

[6:16:00]
So, we will give you a 10-minute break and then reconvene here at 4.15, and then we will resume the questions for these two presentations at 5 o'clock after the public comments.

Break Announcement

Thank you.

[6:25:05]
So, it's 4.15, so I ask you to please take your seats.

Reconvene and Change in Plan

Can we – we're going to continue now, so please have a seat. So, there's a little bit of a change in plan here. Before we do the public comment, there's a rule that we have to present the draft votes, and before we present the draft votes, there's a rule we have to see here the updates and summary of the evidence to recommendation.

Presentation of Draft Votes and ETR Summary

[6:26:09]
We will postpone the vote until tomorrow, so that will not happen today, but what we will do now is we will hear from Dr. McNeil and Dr. Peacock, and then we'll present the draft vote, and we will have then the public comments after that. And I've asked Dr. McNeil to do that as quickly as possible, and if there are any questions on his presentation, we will also do those tomorrow.
[Ben Spader]
Thank you, and I'll do my best to run as quickly as possible, and I would – I do want to make sure that all this information is available to be weighed for the vote, so noting you all have the material, and there'll be opportunities to review further leading up to the vote.

ETR Summary for Clostrovimab

So, I will try to go quickly. The policy question under consideration for today, should a CLOS-ROBO-MAB be recommended for all infants less than eight months of age during or entering the first R3 season?

[6:27:11]
ACIP utilizes evidence to recommendation framework to structure evidence into a set of domains, both for the workgroup and the committee to consider when making immunization recommendation. Today, I will present evidence for each domain listed on the slide. The equity domain was presented in April, and in the interest of time, I will not cover it today. However, slides and a recording are available on the CDC website. The first domain is public health problem.

Public Health Problem Domain

The evidence presented in this domain is intended to inform the question, is RSV-associated disease among infants less than eight months of age a public – of public health importance? The burden of RSV in children is high. In the absence of RSV preventer products, CDC estimates in the United States, RSV leads to 2 million medical encounters, 58 to 80,000 hospitalizations, and 100 to 300 deaths in children under five years of age.

[6:28:08]
In the absence of RSV preventer products, most infants are infected in their first year of life. And among young infants, 2 to 3 percent will be hospitalized to the RSV. Highest hospitalization rates occur in the first year of life, and the risk declines as children get older. Approximately 80 percent of infants hospitalized for RSV have no underlying medical conditions. Therefore, all young children are considered at risk for severe RSV disease. When asked, is RSV associated among – is RSV disease among infants under eight months of age a public health concern, the work group unanimously voted yes. The second domain is benefits and harms.

Benefits and Harms Domain

Data in this domain should inform three questions. How substantial are the desirable anticipated benefits? How substantial are the anticipated undesirable effects?

[6:29:01]
And do the desirable effects outweigh the undesirable effects? To assess the benefits and harms of immunization with – to assess the benefits and harms of receipt of Clostromab, we conducted a great analysis, an approach to evaluate the certainty of the effects for both beneficial and harmful outcomes. To define the scope of the great assessment, the policy question was reframed as a PICO question.

GRADE Analysis

The population is – of interest is all infants under eight months of age who are born during or during their first RSV season. The intervention is Clostromab. The comparison is no immunization. The potential beneficial outcomes included in the great assessment were RSV associated medical attendant lower respiratory tract infection, RSV associated LTRI and hospitalization, RSV associated LTR and ICU admission, all caused medically attended LTRI, all caused LTR associated hospitalization.

[6:30:07]
The potential harmful outcome evaluated was serious adverse events.

Certainty Assessment

As a short refresher, a certainty assessment reflects our confidence that the true effect lies close to the estimated effect. Here are the outcomes, their importance, and the data sources used for grade. There was one study that met the inclusion type criteria for the PICO question and was used to evaluate all the outcomes. This was Merck's phase 2b3 double-blinded randomized placebo-controlled trial.

Beneficial Outcomes Efficacy and Certainty

The full grade benefits can be found in the slides posted online from the ACI meeting, but I'll review high-level results. For beneficial outcomes, we assessed efficacy estimates from the trial through 150 days along with certainty estimates.

[6:31:03]
I'll follow up on the critical outcomes, which are boxed in red. For RSV associated medical attended LTRI, the efficacy was 50% at 60%. In the certainty assessment, there was concern for indirectness because the trial excluded infants who were placebo eligible and took place during a season with disrupted RSV circulation due to COVID-19. These concerns were deemed not serious, but they were noted for all the outcomes. This concern, the concern noted for all outcomes was judged to not be serious. For RSV associated LTRI with hospitalization, the efficacy was 91%. For RSV associated LTR with ICU admission, the efficacy was estimated to be 100%.

Harms (Serious Adverse Events)

For harms, we evaluated the relative risk of serious adverse events in the trial through 360 days.

[6:32:05]
The estimated relative risk had a 95 confidence interval that ranged from .77 to 1.2, so included one. This suggests that serious adverse events occurred at a similar rate in clostrobromab in the placebo groups. However, there was a serious concern for imprecision in this estimate.

Summary of GRADE Findings

This slide summarizes great findings in the final evidence certainty ratings. Clostrobromab was found to be effective in preventing RSV associated medically attended LRTR and RSV associated hospitalization with high certainty. It was effective in preventing ICU admissions due to RSV associated LTR, LRI with moderate certainty, ineffective in preventing all-cause medically attended LRTI with moderate certainty, moderately effective in preventing all-cause hospitalization with LTRI with high certainty.

[6:33:02]
Finally, there was no observed increase in serious adverse events in the clostrobromab group compared to the placebo. I'll now discuss additional information relevant to the benefits of clostrobromab that were not included in GRADE.

Additional Information Relevant to Benefits

Participants were followed through 180 days for two outcomes, RSV associated medically attended LRTR and RSV associated LRTI with hospitalization. While the efficacy appeared to be sustained through 180 days, based both on the point estimates and the 95% confidence intervals, very few cases were added either to the clostrobromab or placebo arms during 151 to 180 days. This was likely due to low RSV circulation during that time period. In addition to clostrobromab trial outcomes included in GRADE, there are other potential benefits of clostrobromab that are important to highlight.

[6:34:02]
If recommended by CDC, clostrobromab would be the second approved recommended long-lasting monoclonal antibody for prevention of severe RSV disease in infants. Having multiple products available with different binding sites will be beneficial in the event that resistant mutations emerge to either product. If one product experiences a supply disruption, this was experienced, as was experienced during the 23-24 season, the availability of the other product can help prevent shortages. Market competition may also help in creating favorable pricing. In addition to serious adverse events, the clinical trials also evaluated solicited adverse events.

Solicited Adverse Events

These are expected short-term reactions like injection site or systemic symptoms reported within the first five days after immunization. The overall rate of injection site and systemic reactions was very similar between groups, 29.9% in clostrobromab arm and 30.9% in the placebo arm.

[6:35:07]
These events were mostly mild grade one or moderate grade two. No grade four events were reported.

Rates of Fever

Rates of fever within the first five days after immunization were also evaluated and are shown in this rate. The rates were comparable between the groups, 3.7% in the clostrobromab arm, 4% in the placebo arm. These data suggest that fever is not increased with clostrobromab use compared to the placebo.

Workgroup Interpretation of Benefits and Harms

Based on the data I presented in this domain, the workgroup felt that clostrobromab was an efficacious long-lasting monoclonal antibody that can prevent severe RSV disease in young infants for the duration of their first RSV season. Clostrobromab is to be the second long-lasting monoclonal antibody prevention product and having two products will mitigate the risk of manufacturing shortages and loss of efficacy due to mutations in the binding site.

[6:36:04]
Clostrobromab has a favorable safety profile with no observed increase in serious adverse events or local or systemic solicited adverse events including fever, but it was noted that rare serious adverse events were unlikely to be detected in this trial due to size. The vast majority of the workgroup felt that the desirable anticipated effects of clostrobromab were large and the undesirable anticipated effects were minimal to small. When polled on the question, do the desirable effects outweigh the undesirable effects, the workgroup unanimously polled that the data favored clostrobromab.

Values Domain

The next domain is values. Data presented in this domain should help the committee answer two questions. First, do parents and caregivers feel that desirable effects of clostrobromab are large relative to undesirable? And second, is there important uncertainty about our variability and how much parents and caregivers value the prevention of severe RSV disease?

Survey Data on Risk Perceptions and Parent Preferences

[6:37:10]
To help inform the ETR values, we looked at a survey data on risk perceptions among pregnant women. This nationwide online survey was conducted in December 2022 to January 2023 among women who were either pregnant or within 12 months postpartum. Thirty-one percent of respondents reported knowing a baby who had been hospitalized for RSV. Forty percent believed that their own baby would become moderately or severely ill if infected. And 69 percent worried their baby would need to be hospitalized if infected with RSV. In an April to May cascadious study conducted of parent preferences for RSV products, among respondents age 18 to 49 with children, parents were asked which product they would prefer if both were available, safe, and effective. Thirty-seven preferred the maternal RSV vaccine.

[6:38:03]
Twelve percent preferred the infant monoclonal antibody. Three percent preferred neither. The largest share, 48 percent, had no preference. These findings indicate no clear parental preference between paternal vaccination of long-lasting monoclonal antibodies, suggesting that either option may be acceptable to parents. This slide shows preliminary data from the National Immunization Survey as of February of this year.

Preliminary Data from National Immunization Survey

Women aged 18 to 49 years with an infant under eight months of age were asked about RSV immunization for their infants. Respondents reported that 50 percent of infants were protected by long-lasting monoclonal antibody, represented in teal. An additional 7 percent reported that they definitely intended to receive a long-lasting monoclonal antibody for their infant, represented in gray.

Workgroup Interpretation of Values

The work group felt that parents and caregivers probably felt the desirable effects of clostrobomab were large relative to the undesirable effects.

[6:39:03]
When asked whether there was important uncertainty about our variability and how much parents and caregivers value the prevention of severe RSV disease, the majority of the work group felt that there was probably not important uncertainty or variability.

Acceptability Domain

I will now present data on acceptability. This domain asked whether clostrobomab is acceptable to key stakeholders, which generally refers to providers or provider and professional organizations.

Survey of Pediatricians

In a survey of 200 U.S. pediatricians conducted in October 2024, about three-quarters of pediatricians reported their practice had offered a long-lasting monoclonal antibody. Over 90 percent of pediatricians agreed or strongly agreed that long-lasting monoclonal antibody is effective for, is safe for infants, is effective against severe RSV disease. They felt confident discussing and recommending the immunization, and they felt comfortable co-administering this immunization with one or more vaccines in a single visit.

Endorsements by Professional Organizations

[6:40:11]
RSV prevention through long-lasting monoclonal antibodies has been endorsed or recommended by national provider and professional organizations, including but not limited to the American Academy of Pediatrics, the American Academy of Family Physicians, and the National Foundation for Infectious Diseases. The work group felt that immunization with clostrobomab is acceptable to key stakeholders.

Workgroup Interpretation of Acceptability

The next domain is feasibility.

Feasibility Domain

Data presented here will inform whether clostrobomab is a feasible intervention to implement among all infants less than eight months of age born during earning the first RSV season. The VFC program is a federally funded program that provides immunizations at no cost to children who might not otherwise be anticipated to be vaccinated due to inability to pay.

VFC Program and Implementation Considerations

[6:41:03]
If ACIP votes to include clostrobomab in VFC, it would consider the second monoclonal and it would become the second monoclonal antibody to be added to the program. There are several implementation pros and cons to consider. Clostrobomab is a single-dose product administered regardless of the infant's weight, which can simplify delivery. Stocking clostrobomab may be challenging for providers who also need to stock nercevumab for high-risk children age eight through 19 months entering their second season. Some providers may prefer to stock only one RSV monoclonal.

Challenges Reported by Pediatricians

In a 2024 survey of pediatricians regarding challenges they experienced or anticipated experiencing when offering long-lasting monoclonal antibody, three most commonly reported challenges after apparent caregiving concerns around safety were, first, challenges knowing maternal RSV vaccination status to determine infant eligibility, which was reported by 34% of all pediatricians.

[6:42:04]
Second, financial burden in purchasing the product. And third, challenges with reimbursement from private healthcare insurance. The majority of the work group felt that clostrobomab is or probably is feasible to implement.

Workgroup Interpretation of Feasibility

Resource Use Domain

The next domain is resource use. Here I will present data intended to help the committee address whether clostrobomab is a reasonable and efficient allocation of resources. A cost-effectiveness model was conducted by the University of Michigan and CDC.

Cost-Effectiveness Model

The model is built off of methods and inputs that were selected to model the cost-effectiveness of nercevumab. The model cost-effectiveness of clostrobomab, to model the cost-effectiveness of clostrobomab, investigators updated key inputs including effectiveness, its waning trajectory, and anticipated cost for dose. On this slide, you can see the results of the modeled base case scenario for an annual birth cohort in which 50% of infants are immunized with clostrobomab compared to an annual birth cohort in which only polizumab is used among eligible high-risk infants.

Modeled Base Case Scenario Results

[6:43:15]
In this scenario, it is approximated that the following events will be adverted. 120,000 outpatient visits, 43,500 emergency department visits, 20,000 hospitalizations, 4,500 ITU admissions, 20 deaths, and almost 3,500 quality-adjusted life years that would be gained.

Incremental Cost-Effectiveness Ratios

Examining the incremental cost-effectiveness ratios or how much this costs to prevent a single outcome, in this model is estimated to cost roughly 3,000topreventoneoutpatientvisit,88,200 to prevent one emergency department visit, 17,500topreventonehospitalization,and80,000 to prevent one ICU admission.

[6:44:06]
And finally, $104,500 per quality-adjusted life year gained.

Sensitivity Analyses and Cost-Effectiveness

I also want to highlight that we did extensive sensitivity analyses looking at a broad range of inputs, which is described on this slide. Overall, the clostrobomab is cost-effective under standard U.S. thresholds in the range of 100,000to150,000 per quality. However, ICRs depend heavily on model inputs for inpatient costs, quality of life losses, and clostrobomab costs. The majority of the workgroup felt that clostrobomab use among all events under eight months of age born during or entering the first RSV season is or probably is a reasonable and efficient allocation of resources at an average cost of $458 per dose.

Workgroup Interpretation of Resource Use

Summary of Workgroup Discussions and Interpretation

[6:45:12]
I will now summarize the workgroup discussions, considerations, and interpretation of the data. The workgroup felt the phase 2b, 3 trial of clostrobomab demonstrated a high efficacy for prevention of severe RSV through 150 days. The workgroup noted that serious adverse events appeared balanced between clostrobomab and placebo arms. At the same time, they acknowledged that rare events are unlikely to be detected in a trial this size. The workgroup discussion also highlighted the following. Although clostrobomab has demonstrated a shorter half-life than nursevimab, the efficacy of clostrobomab against severe RSV appeared sustained through 150 days.

[6:46:07]
Differences in trial endpoints made direct comparisons between the two products challenging. A head-to-head trial would be needed to directly assess comparative efficacy. The workgroup highlighted the benefits of multiple long-lasting monoclonal antibody products in multiple manufacturers. This diversification offers key advantages. If RSV develops resistance to one product or if there is a supply chain issue, another option remains available. It may also encourage price competition, potentially lowering costs over time. Finally, RSV is the leading cause of hospitalization in infants, and this burden can be reduced through immunization. However, to have meaningful public health impact, timely administration is essential. For infants born outside of the RSV season, high uptake prior to season onset is critical. For infants born during the RSV season, administration should be within the first week of life, ideally during birth hospitalization.

[6:47:08]
When asked, what is the balance between desirable and undesirable effects?

Balance Between Desirable and Undesirable Effects

The workgroup concluded that the desirable consequences clearly outweigh the undesirable consequences. And in the final poll, when asked, should Clostrobabab be recommended for all infants less than eight months of age born during or entering their first RSV season, the workgroup unanimously supported recommending the intervention.

Final Poll on Recommendation

Acknowledgments

I would like to, again, thank the many, many collaborators who contributed to this presentation, including both experts at CDC and external experts. Kayessa, Chair, would you like to move on to the clinical considerations?

Clinical Considerations for Clostrovimab

[6:48:03]
Okay. You key up the next presentation, please. Next, I will discuss the proposed clinical considerations for Clostrobabab. As a reminder, Clostrobabab was approved by the FDA earlier this month. The following slides refer to proposed clinical considerations for Clostrobabab if recommended by ACIP. I will discuss the workgroup considerations and interpretations of uptake, safety, effectiveness, and impact studies, and then review clinical considerations, including Clostrobabab.

Workgroup Considerations and Interpretation

Recommendations compared with Nirsababab and Clostrobabab storage, handling, and administration.

[6:49:01]
To summarize the effectiveness, uptake, and impact data, Nirsababab was effective against RSV-associated ED encounters, hospitalization, and critical illness among infants in their first RSV season. Paternal vaccination was effective against RSV-associated ED encounters and hospitalizations. An estimated 50% of infants were either born to vaccinated mother or received Nirsababab. Compared with prior RSV immunization introduction, RSV-associated hospitalization rates were reduced by 30 to 40% among eligible infants, and by half among infants age zero to two months. The workgroup noted the impact of RSV immunizations to decrease severe RSV disease in infants during the 24-25 RSV season in the RSV net and VSN networks is clear. Increasing uptake is important in order to further reduce burden of RSV disease.

[6:50:02]
Higher impact has been seen in other countries that have attained higher uptake of these immunizations. It is important to maximize availability of RSV immunizations, including providing infant RSV antibody during the birth hospitalization. The increase in birthing hospital enrollment in the VFC program is important, and challenges remain, and we want to continue to increase that, continue to increase enrollment. To summarize the FAERS database, post-marketing, adverse event reporting, and error reporting with Nirsababab.

FAERS Database and Adverse Event Reporting

During the reporting period since approval in March 31, 2025, the most frequently reported adverse events involved patients who developed RSV infections despite prior receipt of Nirsababab, and included signs, symptoms, or complications of these infections.

[6:51:01]
No product safety labeling updates have been made since serious hypersensitivity reactions with Nirsababab were added on February 23, 2024. No additional safety signals have been identified at this time. Errors involving incorrect nirsevimab dose and incorrect product continue to be reported. FDA will continue routine pharmacovigilance of nirsevimab. Earlier, VSD nirsevimab safety study is presented.

VSD Nirsevimab Safety Study Summary

It included almost 40,000 infants that received nirsevimab during the 24-25 season and used a self-controlled risk interval study methodology. No increased risk observed for seizures, immune, thritis, thrombopedia, drug reaction, sepsis or fever were observed. No cases of anaphylaxis and 18 cases of allergic reaction were reported, primarily hives. The workgroup found that FAERS and VSD safety data are reassuring and emphasize that continued monitoring of safety is important.

Workgroup Interpretation of Safety Data

[6:52:08]
To summarize the VSD maternal vaccine study, the study matched a cohort of 14,000 pairs of vaccinated and unvaccinated pregnant women.

VSD Maternal Vaccine Study Summary

No increased risk was observed for most outcomes. An association of maternal R3 vaccine and hypertensive disorders of pregnancy overall and preeclampsia was found. The severity of HDP was similar among vaccinated and unvaccinated. VSD noted that there was potential residual confounding. For example, including parity of the propensity matching and outcome misclassification due to the difficulty in determining the timing of when HDP first occurs and the lack of chart review. The workgroup felt that overall study findings were reassuring, including the lack of association of preterm birth and vaccination.

Workgroup Interpretation of Maternal Vaccine Study

[6:53:07]
The workgroup continues to feel that benefits of maternal R3 vaccination clearly outweigh the potential risks. The workgroup was split on importance of the association of vaccination and hypertensive disorders of pregnancy. Some were not concerned about this association since the effect was small and there was no increased severity in vaccinated versus unvaccinated women with hypertensive disorders of pregnancy and no overall association of vaccination with preterm birth. The American College of Obstetricians and Gynecologists was in agreement with this opinion.

Clostrovimab Product Information

Clostrobomab is a long-lasting monoclonal antibody manufactured by Merck. It is a type of passive immunization.

[6:54:00]
It is administered as a single dose of 105 milligrams in a .7 milliliter syringe with the same dose recommended for all infants born during or entering their first RSV season, regardless of weight. Transitioning now to clinical considerations, the recommendations for clostrobomab intercevumab are to be the same for use in infants younger than eight months born during or entering their first RSV season.

Proposed Clinical Considerations (Recommendations)

There is no preferential recommendation for use of clostrobomab versus intercevumab. However, only clostrobomab is recommended for children ages 8 through 19 months who are at increased risk of severe RSV disease in entering their second RSV season. This is because clostrobomab has not been, not yet been approved for this age group or indication. Infants eligible to receive intercevumab when entering their second RSV season could have received intercevumab or clostrobomab for their first RSV season.

[6:55:01]
There is no effectiveness or safety concerns for using clostrobomab for an infant's first RSV season and intercevumab for their second RSV season. For the proposed use of RSV antibody immunizations in infants, meaning either intercevumab or clostrobomab, these recommendations are largely unchanged from current intercevumab recommendations.

Proposed Use of RSV Antibody Immunizations in Infants

One dose is recommended for infants younger than eight months of age during or entering their first RSV season. The mother, meaning the administration window is during October through March in most of the continental United States. If the mother did not receive RSV vaccine during pregnancy, the mother's RSV vaccination status is unknown or the infant was born less than 14 days after maternal RSV vaccination. RSV antibody may be considered for infants born to vaccinated mothers when infants are

[6:56:01]
in their first RSV season and born to mothers who may not mount an adequate immune response to vaccination, born to mothers who have conditions associated with reduced transplacental antibody transfer, for infants who have procedures leading to loss of maternal antibodies, or for infants with substantially increased risk for severe RSV disease. Today's focus has been on infant RSV antibodies.

Two Immunization Options

However, there are two immunization options to prevent severe RSV in infants. Most infants will not need both maternal vaccination and RSV antibody. Pregnant women with their healthcare provider should choose one of the options. Maternal RSV vaccine is recommended during September through January, and infant RSV antibodies are recommended during October through March. Optimal timing for infant RSV antibody administration is shortly before season for those babies who are already born before October.

[6:57:08]
In jurisdictions with differing RSV seasonality, providers should follow state, local, or territorial guidance on the timing of administration.

Administration Errors

Errors have been reported of giving RSV immunization products to the wrong population. The only RSV immunization to be administered to infants is an RSV antibody. The RSV vaccines, including Abrisbo, Arexi, and mResV should not be given to children. Only Abrisbo should be given to a pregnant woman. Arexi and mResV should not be given to pregnant women. Older adults can receive any of the three approved RSV vaccines. RSV antibodies should not be given to pregnant women or older adults.

Clostrovimab or Nirsevimab and Palivizumab

[6:58:02]
Regarding Clostrobamab or Nercevamab and Pulisimab, if Clostrobamab or Nercevamab is given to an infant or a child, then Pulisimab would not be recommended for the same RSV season. Clostrobamab administration will be the same as for Nercevamab.

Clostrovimab Administration

It will be given as an intramuscular injection to the vastus lateralis muscle of the anterior lateral thigh. The gluteal muscle should not be used. Simultaneous administration of infant RSV antibodies with vaccines is acceptable. Clostrobamab storage and handling recommendations are to store the product at refrigerator temperatures.

Clostrovimab Storage and Handling

Use within 48 hours of removing from the refrigerator. Clostrobamab should not be frozen, should not be shaken, and should be protected from light. The proposed recommendation to report suspected adverse events after Clostrobamab mirror those for Nercevamab.

Proposed Recommendation to Report Adverse Events

[6:59:05]
If RSV antibodies administered alone, please report suspected adverse events to MedWatch. If RSV antibodies administered simultaneously with any vaccine, please report suspected adverse events to the vaccine adverse event reporting system. Additional reporting to MedWatch is not necessary.

Acknowledgment

Thank you.
[Dr. Martin Kulldorff]
Thank you. And the next thing is to propose recommendations.

Proposed Recommendations

Yes, please. So, we are saving questions for probably tomorrow.
[Ben Spader]

[7:00:00]
The first proposed, sorry, Dr. Zadeh, you joked me. Okay. The first proposed recommendation, ACIP recommends infants aged less than eight months born during or entering their first RSV season who are not protected by maternal vaccination receive one dose of Clostrobamab.

First Proposed Recommendation (Clostrovimab)

Proposed Recommendation for VFC Resolution

[Dr. Georgina Peacock]
The proposed recommendation for the VFC resolution is to approve the updated Vaccines for Children VFC resolution for the prevention of RSV.
[Dr. Martin Kulldorff]
And do you have the text of that proposed resolution?

Text of Proposed Resolution

[Dr. Georgina Peacock]
I do. There's a slide set that I need to go through that shows updates to the VFC resolution update.

[7:01:00]
Is that after this? Okay.

Updated VFC Resolution Update

So, I'm going to now go through the updated VFC resolution update. And so, what you'll see first is that the changes to the currently approved VFC resolution language are going to be shown in orange font and the existing language is shown in black font. So, the purpose of the resolution is to update the resolution to include an additional RSV long-acting monoclonal antibody. The first component of the resolution addresses RSV maternal vaccine and there are no changes to eligible groups. There are no changes to the recommended schedule and intervals.

[7:02:00]
However, the individual product name was replaced with a product group name because now there are two products available. There are no changes to the dosage, contraindications or precautions. The second component of the resolution has been retitled to refer to a product group name rather than an individual product name. The eligible groups are unchanged. The list of children at increased risk for severe RSV disease is unchanged. For the recommended schedule and intervals, information about nircivumab is unchanged. However, a new row has been added to the table to reflect the quezirovimab, the newly licensed RSV long-acting monoclonal antibody. As previously discussed and noted in this table, the product is not indicated for the second RSV season.

[7:03:09]
Table notes have been added to the table of reference alternative products providing the definition of long-acting monoclonal antibody and to provide a link to the published information with additional details about the timing of administration. The language below the table has been updated to replace the individual product name with the product group name. There's no changes to the dosage contraindications or precautions. And the final slide notes that ACIP recommendations published within six months following the resolution are incorporated by reference into the resolution other than for the eligible groups. Thank you.
[Dr. Martin Kulldorff]
Thank you very much.

Acknowledgment

[7:04:04]
And again, we will leave questions for later. And I think we can now go on to the public comments.

Public Comments

And I would like to apologize for the delay. Thank you for patiently waiting.

Public Comment Period Begins

We have 10 persons who will comment. And you have three minutes each. And the first person to comment is Kim McRosenberg.

Kim McRosenberg (Children's Health Defense)

Please go ahead. Do we have Kim McRosenberg on the line?

[7:05:00]
If you're speaking, you're on mute.

Kim McRosenberg Comment (Audio Restored)

[Dr. Naomi Joseph]
Yes, I apologize. I was on mute. Thank you very much. I appreciate the opportunity to address you this afternoon. I am general counsel at Children's Health Defense, a nonprofit dedicated to safeguarding children's health. And I'm here to address a critical issue, the misuse of ACIP's best practices guidelines by many states, including large states like California and New York, to recklessly restrict medical exemptions for school vaccine requirements where a treating physician has identified a risk. ACIP guidelines define contraindications and precautions broadly as conditions that increase risk of serious adverse reactions or compromise vaccine efficacy. ACIP has acknowledged these guidelines are not exhaustive and cannot define all reasons a child may need a medical exemption. Yet many states and schools are overriding treating physicians' clinical judgment, limiting exemptions to only those based on reasons explicitly listed in the non-exclusive tables, or going even further, accepting only anaphylaxis as a valid exemption, ignoring other serious risks or reasons that a vaccine might need to be deferred.

[7:06:04]
With many new members in place, the ACIP must now act to prevent continued harm. I urge you to amend the best practices guidelines or issue clear public statement on your website affirming that CDC is not authorized to give medical advice about what an individual child may need to stay safe, that the guidelines are not exhaustive and cannot define every reason for a medical exemption, and only treating physicians using CDC guidance, other evidence, patient and family history, their clinical judgment, and any other information relevant to an individual child's health should determine if an exemption is warranted. Without your action, misapplication of the ACIP guidelines will continue to have devastating consequences. One of the many examples is the case of Sarah Doe, a 16-year-old from New York, with acquired von Willebrand's disease, autoimmune hypersensitivity, unexplained periodic paralysis, and uncontrollable anaphylactic rash, a history of severe vaccine reactions. Six licensed physicians certified that a third hepatitis B dose could endanger her life, yet her school district rejected these exemptions, demanding anaphylaxis within 15 minutes of her last dose as the sole criteria.

[7:07:11]
She desperately wanted to attend school and even tried to get vaccinated at a walk-in clinic after she was denied medical accommodation and kicked out of school. But even that clinic physician found her ineligible because of her condition. Still, the school and state maintain that she cannot be accommodated from taking that third dose of hepatitis B vaccine because her conditions are not listed by ACIP as clear contraindications. She's not alone. CHD and the attorneys with whom we work get calls like this every week. Children not only are being deprived of federally protected disability rights, but some have been badly injured after they were forced to take vaccines against medical advice so they could attend school. And physicians are harmed by this narrow reading, as some of these states are using the ACIP guidance educadual to threaten doctor's licenses if states do not think a recommended exemption meets criteria.

[7:08:00]
Clarification of the guidelines will protect children and ensure physician autonomy. Your timely action is needed this summer to safeguard vulnerable students. Thank you for your time and consideration.

Chrissy Giuliano (Big Cities Health Coalition)

[Dr. Martin Kulldorff]
Thank you very much. The next comment is from Chrissy Giuliano.
[Ashley Halberner]
Good afternoon. Thank you for the opportunity to provide public comment today. My name is Chrissy Giuliano, Executive Director of the Big Cities Health Coalition, which is made up of leaders from 35 of the country's largest metropolitan health departments. We are disappointed in Secretary Kennedy's recent decision to dismiss without cause all 17 prior ACIP members. Among them was my colleague and BCHC board member, Dr. Mashika Roberts, Health Commissioner for the City of Columbus, who is scheduled to join the committee in July. Local health departments play an important role in vaccination.

[7:09:00]
So many people in communities across the country go to their health departments, not just for vaccines, but to get their questions answered and concerns addressed by people they know and trust. Our members and their colleagues across the country take this responsibility seriously, and they do it every day. In the same way that residents look to public health leaders for vaccine advice and guidance, they look to ACIP for vaccine recommendations. But with all due respect to the new committee members, there is genuine worry about whether that will remain the case. For more than 60 years, ACIP has provided independent, science-based, nonpartisan, and objective vaccine recommendations. Clinicians, health departments, and families across the country rely on these recommendations. At a time when trust in public health is already low, the sudden dismissal of an entire committee will only cause additional confusion and distrust. Vaccines are one of public health's greatest accomplishments.

[7:10:02]
They prevent disease and save lives. Before widespread vaccination, nearly one in five American children died before their fifth birthday. The most common cause was infectious diseases that are now preventable. For a time, because of advances in vaccine science and immunization rates, diseases like measles and polio were eliminated in this country. But as we've seen with measles over the past few months, vaccine-preventable diseases are making a comeback, and some children have already died as a result. ACIP recommendations are critically important. They ensure that vaccinations are covered by most insurance plans and that children without insurance coverage can still receive them. The Big Cities Health Coalition is deeply concerned that many routine vaccines may soon become inaccessible or unaffordable for millions of Americans if ACIP makes changes based on ideology rather than science.

[7:11:00]
The stakes are simply too high to let that happen. We urge and expect the new members of this committee to do what ACIP has always done and what health department officials do every day. Follow the science, support the evidence, and make decisions that are in the best interest of the public's health. Thank you again for the opportunity to provide comment.

Mary Koslap-Petraco (Pediatric Nurse Practitioner)

[Dr. Martin Kulldorff]
Yes, thank you. The next presenter is Mary Koslap-Petraco. Please go ahead and welcome.
[Dr. Mary Koslap-Petraco]
Thank you. Good afternoon. I'm Dr. Mary Koslap-Petraco, pediatric nurse practitioner. I've been a PNP for over 30 years and I'm grateful for this opportunity. The scientific and medical community and public health communities are losing faith in the ACIP because of the bogus reasons that were used to dismiss the 17 members. These members have the expertise to design vaccine studies.

[7:12:02]
It is clear that the current members do not have this expertise. Bayer's data has clearly been misinterpreted by this committee. It only offers signals and does not cause causality. The vaccine safety data link is where the actual studies are conducted. And to say that children do not need COVID vaccines is a mistake. I have children in my own practice who have long COVID and were not vaccinated. The vaccine needs to be available for those who want it. Parents have been totally misled by the myths and disinformation that they are seeing on the Internet among other places. They lose faith in their primary care providers and do not seek their advice. I pride myself on answering the questions my patients' parents have. The real enemy here are the viruses and bacteria that are no longer familiar to parents because of the success of vaccines. If the vaccines become less available or used less because of confusion and fear caused by these unscientific changes and the rhetoric coming from DHHS will people will become very aware of the presence of these diseases because they will specifically see children die suffer and die.

[7:13:05]
I live on Long Island in New York and I've walked through old churchyards and I saw all row after row of tiny headstones of children who died before their fifth birthday. I saw older children's headstones as well. The causes of their deaths were noted on the stone. Measles polio tetanus diphtheria whooping cough. Do we really want to witness this again. I will leave it to all of you to explain to the parents why their children did not have access to lifesaving vaccines. My own mother had polio in 1923 and developed post-polio syndrome later in life. My sister's immune system was permanently damaged from measles which she had in 1959. I do not want other families to suffer as my family has. My own children and grandchildren all had these vaccines and they have grown up safe and healthy. I want all children to have the same opportunity to grow up safe and healthy and free from vaccine preventable diseases. I'm a VFC provider. Please continue to offer these vaccines so that all children have access to lifesaving vaccines.

[7:14:06]
Thank you for this opportunity.

Marcia Cohen-Sakai

[Dr. Martin Kulldorff]
Thank you for commenting Dr. Khosla Petrako. The next person is Marcia Cohen-Sakai.
[Marcia Cohen-Sakai]
Hello. First a question. Was it necessary to purge this panel of all 17 duly vetted experts. Was it because according to Dr. Macri ACIP is a kangaroo court that rubber stamps or was this purge unjustified and unthinkable. If Senator Cassidy is concerned about a lack of expertise and anti-vaccine bias among the newly appointed members how can I a lay person consider it reasonable for all 17 members whose expertise is indisputable to have been terminated.

[7:15:01]
This week the California Medical Association the American Medical Association and more than 100 national and state medical organizations submitted a letter to the HHS secretary demanding the immediate reinstatement of all 17 ACIP members. Their removal threatens public confidence in vaccines and risks the destruction of the success vaccines have made in controlling preventable diseases and saving lives. Over the years ACIP experts have provided evidence based vaccine recommendations for FDA approved vaccines through a transparent public process. They have been vetted and appointed through a transparent public process. Without them we are left with a vacuum filled with doubt and confusion that will likely lead to untold preventable illness disability and death among health care providers and patients of every age and vulnerability along with all the people they live with work with study with and care for.

[7:16:06]
ACIP recommendations determine insurance coverage decisions. So we need vaccine experts who will ensure widespread unhindered access to FDA approved vaccines like flu measles HPV RSV and COVID. Even as we speak the U.S. is beginning a summer wave of COVID and measles outbreaks are increasing globally. No child should die of measles or have their immune system shattered. No one should have their life devastated by acute or long COVID. The safe and effective vaccines we have help prevent such tragedies. The scientific evidence has been clear for a very long time. Our trusted vaccines have proven themselves to save lives and prevent severe disease disability and death. We need the expert recommendations of the ousted ACIP members to ensure the continuity and accessibility of vaccine protection in the United States.

[7:17:05]
Thank you.

Caroline Brown (Pediatrician)

[Dr. Martin Kulldorff]
Thank you for taking the time to speak to us. The next presenter or commenter comes from Caroline Brown. Please.
[Caroline Brown]
Sorry I'm meet with my nutrition practicing in North Carolina. I've cared for cared for children in this community for nearly two decades and I've seen what vaccine preventable diseases do to otherwise healthy kids. I've treated infants with blue faces gasping for breath from RSV and pertussis. Children in the ICU paralyzed brain damaged or missing limbs from illnesses we now have vaccines to prevent. When I trained in the early 2000s we routinely performed spinal taps on infants with fever to rule out meningitis.

[7:18:05]
But thanks to vaccines like Hib and pneumococcal most of those children were spared devastating outcomes. My older colleagues have countless stories from the 80s and 90s of children who weren't so lucky. Whose bodies were ravaged by these diseases and whose suffering still haunts those doctors decades later. Now 18 years into my own practice I watch with heartbreak as the public's trust in vaccines erodes. Ironically just yesterday the first confirmed case of measles was announced in my own state here in my own county. So I've spent the past 24 hours responding to panicked parents worrying about their young children. We must acknowledge that measles spread throughout our country is our reality today only because of the fear mongering and pseudoscience that has overtaken our country. Remember measles was completely eradicated from the United States 25 years ago and is back now because of declining vaccine rates fueled by misinformation that is not only allowed but amplified by voices of some of you sitting on this very committee.

[7:19:04]
The parents of the children I care for are frightened watching health policy shift from evidence to ideology and from science to self-interest. I understand skepticism. Medicine must earn public trust. But let me be clear. Vaccines are the most rigorously studied safest and most effective medical intervention of the 20th century. There is no legitimate scientific debate about the risk versus benefit of vaccines nor is there any link between vaccines and autism. Furthermore the fact that thimerosal is on the agenda for tomorrow's meeting is particularly concerning given that it was removed from virtually all routine pediatric vaccines in this country over 20 years ago. As American citizens pediatricians understand and respect the deep value our country places on individual freedom. We understand for politicians it's easiest to say let the people choose for themselves but the choice stops being personal when one family's decision to not vaccinate means another child they pass in the grocery store becomes infected with a potentially deadly disease.

[7:20:09]
As Dr. Paul Offit says there is no risk free choice. The danger isn't the vaccines it is the disease. Pediatricians are passionate about vaccines because we have witnessed the horrific suffering that can occur in their absence. But like a gardener who thinks no weeding is needed when they see no weeds without proper tending if herd immunity declines these diseases will crop back up and the damage will be devastating. Thank you.
[Dr. Martin Kulldorff]
Thank you for your comments.

Alexandra Jones-Packham (Medical Student)

The next comments are from Alexandra Jones-Packham. Please.
[Lexi Jones-Packham]
My name is Lexi Jones-Packham. I just graduated medical school and I'm starting my residency in internal medicine and pediatrics right now actually. In undergrad I majored in microbiology with a particular interest in immunology and vaccines.

[7:21:02]
I am also pregnant and will be due in the middle of respiratory season. It's a very exciting time for any new mom but as a new pediatrician as well I have some extra perspective on how dangerous respiratory season can be for newborns. In medical school I rotated for several weeks in the pediatric ICU during the winter and I saw so many bronchiolitis cases specifically from RSV and influenza. Unfortunately we don't have many effective treatments against these respiratory viruses so we just have to offer all the supportive care that we can while their body fights off the infection. As a doctor and as a future mother it is so hard to watch these babies struggle to survive these infections when we have vaccines and the RSV antibodies that are so effective at preventing these infections. I believe you heard the evidence today on the effectiveness of some of these vaccines and antibodies and anecdotally every patient that I saw during my time in the pediatric ICU with a respiratory infection had not been vaccinated against the pathogen that they were infected with whether because of parental choice or because they were too young to qualify for that vaccine yet.

[7:22:13]
Children who do receive these vaccines are much less likely to get severe disease from these infections. As a soon to be mother and as a pediatrician I will be electing to get the RSV flu and COVID vaccines during my pregnancy and will ensure that my child gets the flu and COVID vaccines as soon as they're eligible as well as antibodies if it's indicated for them. I want to make sure that all of my patients parents have the opportunity to discuss these vaccines with me as their pediatrician and especially to have these covered by insurance if they do choose to get them. Thank you for your time.
[Dr. Martin Kulldorff]
Thank you for those comments and the next presenter is Rosalie Bright.

Rosalie Bright (Initial Technical Difficulties)

Please go ahead.

[7:23:08]
We cannot hear are you on mute.

Diana Figueroa (Nurse)

So we're going to go on to the next comments from Diana Figueroa.
[Diana Figueroa]
Hello. Good afternoon. I want to say thank you for allowing me the time to speak today. My name is Diana Figueroa and I have been a nurse for 16 years as an LVN. I've specifically been a pediatric LVN for 14 of those years. I believe I can speak for many of my fellow LVNs and LPNs that the termination of the 17 ACIP members is a poor decision as these members have gone through a thorough vetting process and have now and shown how knowledgeable and intelligent they are in making vaccine decisions for our country using evidence-based science.

[7:24:04]
Our country and healthcare organizations have valued all the hard work and time that goes into the thoughtful decisions that the 17 ACIP members have made in the past until April of this year. The recent decisions made without the consultation of ACIP shows the danger that our country will be facing when the non-medically trained individuals and those who have not been vetted appropriately attempt to make decisions and recommendations that are not at the best interest of our country as a whole using evidence-based science but only making decisions based on their own opinions and for the 0.1 percent of people who do not agree with the ACIP's previous decisions. The current lack of transparency is very troubling. I also believe that this is that that decisions like shared clinical decision making is a major barrier preventing LVNs and LPNs like myself from providing requested vaccines to patients which then end up leading to delays in care. Our healthcare system is very overwhelmed with needs from our patients and as we believe that preventative care is essential to prevent costly hospital stays from chronic and non-chronic illnesses and providing immunizations as a preventative care measure.

[7:25:09]
There should never be barriers to providing a lifesaving vaccine for any communicable disease that can be prevented with an available vaccine in our country. I ask that the FDA and the CDC not create more barriers in providing valuable and important vaccines to our patients from our pregnant women to our newborn babies to our immunocompromised and our elderly who are all at high risk but also to our healthy individuals like myself who desire to be vaccinated to protect my friends and family around me as well as any patients I may encounter. We share the sentiments across many medical organizations to ask to reinstate the interminated ACIP members to full capacity within the ACIP so that they can continue the great work they have done in the past and remove the eight recently unvetted appointment appointed members but also to leave the current pediatric and adult vaccination recommendations as they are returning the COVID vaccine recommendations for our pediatric patients and our pregnant

[7:26:00]
individuals to the previous recommendations as it has proven to be successful in disease prevention. Thank you for your time.
[Dr. Martin Kulldorff]
Thank you for those comments and we'll move going on to Amy Hardin.

Amy Hardin (Pediatrician)

Please go ahead.
[Dr. Laura Morris]
Hi I'm Dr. Amy Hardin. I'm a pediatrician in Woodstock Georgia. I trained at Emory from 1990 to 1993 spending two thirds of my time at Grady Hospital and the rest right across the street at Eglinton from the CDC. Back then before we had Homozygous Influenza type B and pneumococcal vaccines we admitted 5 in 10 children every night under the age of 3 with fevers above 101 and nuclear sores. These children underwent full septic workups including blood cultures catheterized urine samples and then a spinal cap to check for life threatening infections like meningitis and sepsis. I remember examining gram stains in the micro lab and writing myself searching for the telltale bacteria which we were dreading to see.

[7:27:04]
Hib and Streptomyeloma. Before the Hib vaccine 1 in 200 kids under the age of 5 developed invasive Hib disease. These infections included sepsis epiglottitis cellulitis and meningitis and they didn't discriminate by income. Healthy and cherished children from all walks of life suddenly became critically ill. Many died others survived but were left with lifelong disabilities deafness cerebral palsy severe learning challenges and many of the kids I cared for with cerebral palsy in the first few decades of my career developed CP due to meningitis. Why do I sleep better on call now. Because these vaccines work. I have not seen a single case of Hib or pneumococcal meningitis or sepsis since 1999 thanks to vaccines against Hib and pneumococcus. Check out the graphs in the CDC pink book of post vaccine diseases. The slope of the precipitous drops of disease post vaccine entry are amazing. And how do I remember this date of 1999. It's because this is the last patient's funeral who I went to in 1999 who died of a vaccine preventable disease.

[7:28:05]
He was a lovely 2 year old little boy whose mom missed his 2 year old checkup because he was sick and then she got busy and forgot to reschedule. He died three months later from pneumococcal sepsis. There's nothing more tragic than the loss of a child from a vaccine preventable disease or a child sized poppin with a large fire truck on it. I'll remember that funeral forever. And to show just how well vaccines have worked and sent in my group of nine pediatricians only two of us have seen children die of vaccine preventable diseases. Because we're the two oldest dots back before work. But sadly now due to vaccine hesitancy and misinformation on the Internet we are seeing these infections again and again and with other terms such as muses from moving pop children are dying. My colleagues in Atlanta are again treating children with meningitis. What do these heartbreaking cases have in common. These children were unvaccinated usually scary misinformation on the Internet. You are now the decision makers in your new role on the ACIP to safeguard America's children.

[7:29:01]
They are your responsibility and mine too. Please don't let us go backwards. Don't make my job a more difficult one. Having to give parents in my practice horrible news when their children develop or both the horrible or preventable disease. We are too smart of a country to relive the tragedies we pediatricians have worked so hard to prevent. Vaccines are safe effective and save lives. Let us not forget this. Thank you.

Adriana Williams (US Citizen)

[Dr. Martin Kulldorff]
Thank you for those comments Dr. Hardin. And the next person is Adriana Williams.
[Adriana Williams]
Hello everyone. I'm US citizen Adriana Williams. Thank you all for being here and allowing me to speak today. I will start off by reminding us of the Hippocratic Oath which stated firmly that doctors will avoid harmful treatments for their patients. Yet it's been noticed that doctors CDC personnel and their colleagues have provided ever increasing access to harm for patients nationwide and even worldwide.

[7:30:02]
The vaccines in discussion today and tomorrow are of no good enough health benefit and are in no way safe enough for members of the public. There are much more safer and effective natural treatments and preventative. Therefore vaccines must be abolished immediately. Vaccines are known to be a bioweapon mechanism. Some don't even know it. Evidence shows that many are systemically medically harmed by all vaccines and the damage has been shown to be done cumulatively over time and in negative interaction with ingredients and adjuvants without bodily functions. You need to do due diligence to address this issue with more integrity than what we have seen. Therefore all vaccines should be abolished in its entirety till the broken system can be fixed. This is serious. VAERS data reports that over 8000 reports were filed and with over 70 deaths over 70 deaths following RSV vaccination.

[7:31:07]
Please do not ignore the evidence the data. It shows RSV vaccines are dangerous. RSV vaccines are harmful. For example look into VAERS report ID 2801021. A person passed away following an RSV vaccination. Sadly that is just one out of many. You look at most of any U.S. currency such as a dollar a coin a part of our legacy you'll see an emblem which transcribes e pluribus unum which translates to one out of many. If you listen to the Stop the Shocks community on X the ones out of many such as the vaccine injured they speak. They share what is happening in reality that people are dying and people are hurting and they want help and restitution from individuals such as yourselves having heroic potential. God bless us all and may you all stand for your duty of the Hippocratic oath to do no harm by not ignoring the data that shows you must stop all vaccines from being administered starting today and tomorrow with the vaccine with the RS vaccination votes.

[7:32:15]
Start with today and tomorrow and make your legacy one of a hero for present and future generations by beginning to save the one out of many from being harmed by vaccines. Please stop the shots recommend them to be stopped all of them. Now help the vaccine injured and thank you.
[Dr. Martin Kulldorff]
Thank you for sharing that with us.

Rosalie Bright (Audio Restored)

We're going to go back and see if Rosalie Bright is available now. I don't think that is the case unless you're on mute. Hello can you speak a little bit louder.

[7:33:00]
It's very very low sound. That's better. Thank you.
[Michelle Lege]
Thank you. Sorry about these problems. Hi I'm Dr. Rosalie Bright. I was a doctoral level epidemiologist at the Food and Drug Administration for most of my career. While there I witnessed many instances when staff and managers wanted to advocate for decisions that quote felt right although the data supported another decision. The importance of scientific data was sustained by the requirement that all of the internal and advisory experts with input needed to document their reasoning for the archived record. I learned from and became able to trust the input of experts in different disciplines who worked on the same regulatory decisions as I did. I believe most of the decisions produced by the system were valid and well-supported. Now that I'm retired my trust in decisions based on confidential data has been shaken in the past several months because of mass federal firings intimidation overruling of scientists by the political appointees and now radical changes to the tried and tested advisory committee system.

[7:34:05]
I can still read and analyze the public research literature to see if I agree with federal decisions. Being elderly I may lose that ability due to my own illness or censorship of publications and decisions. I won't be able to act in my best interest if the federal government restricts my access to treatment or other measures. Federal guidance is crucial because most people including healthcare professionals can't or won't read the scientific literature for themselves and rely on the guidance from FDA and CDC. My requests are one continue to consider long COVID incidents and severity when recommending COVID-19 vaccine schedules. Two recommend universal access to FDA approved COVID-19 vaccine three times per year. Three call for development of more effective COVID-19 vaccines. Four provide ACIP meeting materials to the public at the same time as to the ACIP members and allow at least a week to file responsive written comments.

[7:35:02]
Five provide summaries and discussion of public comments at the meetings. Six allow more and longer oral public comments at the meetings. Seven reinstate the 17 ACIP members that had been let go. Eight require ACIP members to show evidence of the ability to perform science-based assessments of reports and studies. Nine bar ACIP membership to those who refuse to follow established principles of clinical and human research ethics. People who conduct human research have generally been required to learn the applicable publicly available ethics guidelines before being allowed to begin their study. Anyone who says they support comparing a vaccine that has already been approved or similar to one that has been approved to an inert placebo is advocating for the violation of the basic ethic against withholding vaccines that are known to work. Such people have no business being on ACIP or in or leading any HHS organization. More details are in my written submission.

[7:36:00]
Thank you. Thank you.

Conclusion of Public Comment Period

[Dr. Martin Kulldorff]
And thank you for to all 10 members of the public for taking the time to speak to us and to give us your comments. So this concludes the public comment period. So again, thank you very much, all 10 of you.

Adjournment for the Day

We did not finish the agenda items for the RSV vaccines. But it is now 530. So it's time for to adjourn for today. And we will reconvene here tomorrow at 8 o'clock in the morning. So I'm looking forward very much to see all of you then and for new important scientific discussions.

Reminder of ACIP Purpose and Evidence-Based Medicine

[7:37:03]
And as the last word today, I was to remind everybody that the purpose of this committee and is to follow evidence based medicine. And that is what we will do. And that is the only way to restore integrity and trust in public health. So thank you very much, everybody.