ACIP Meeting Day 2

27 June 2025

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[Martin Kulldorff]

[0:20:28]
Good morning, everybody, and welcome back to the June 2025 ACIP meeting.

Welcome and Roll Call

Today is June 26th, 2025, and we're going to start with a roll call, so do you want to administer that?
[Unknown]
Sure.
[Robert Malone]
So we just wanted our members to quickly introduce themselves.
[Martin Kulldorff]

[0:21:01]
So I am Martin Kulldorff.
[Joseph Hebelin]
Joseph Hebelin.
[Robert Malone]
Robert Bloom. James Pagano.
[Martin Kulldorff]
Retef Levy. And we have two members remotely, I believe.
[Vicky Pebsworth]
Vicky Pebsworth.
[Cody Meissner]
Good morning. This is Cody Meissner.
[Martin Kulldorff]
And we have a slight change in the agenda.

Agenda Change: RSV Discussion and Vote

We did not finish the discussions of the RSV yesterday, and we are going to, I believe, today, we will do just a five-minute presentation on that, and then we'll leave that for the next meeting and the rest of that.

[0:22:09]
So back to the RSV, we have two votes to be made, but we didn't finish the discussion yesterday. So I just want to stress that most of the presentations yesterday was mainly about the maternal vaccination, as well as the already approved DSRVMAP monoclonal antibody. The thing that we are voting on is not neither of those two products. We are voting on a second alternative monoclonal antibody, so it's not a vaccine, it's a monoclonal antibody called Klesrovimab. But I want to give the members here opportunities to ask questions about the presentations yesterday and have a discussion about this, so please, Dr. Levy.

Discussion on RSV Monoclonal Antibody Safety Data

[Retef Levy]

[0:23:03]
So good morning, everybody. First let me thank again for the very detailed presentation yesterday about the RSV products. I think it's very, I think there's a consensus that RSV is a serious illness that poses risks to babies, especially young babies in their early stages of life, and particularly to vulnerable babies that have either some comorbidities and underlying conditions or early preterm birth. So I think that we are all hopeful that these therapies are going to allow us to provide them better care and hopefully prevent serious hospitalizations and deaths. That said, I think that we now have two products, one that is already approved and one that

[0:24:05]
we are about to approve, and I took the opportunity to look through what the clinical trials that were conducted on all of these products suggest, and I would like to share what I, share data that I found and would be very happy to hear the reactions of our colleagues at the CDC about what do they make out of that data in terms of safety concerns. So the main phase three trial of, that was conducted on healthy children on the previous product, the nirsamivab, it was the Melody trial, and it was conducted in a ratio of two to one for the immunized children and babies. The number of deaths in that trial were five in the immunized children and zero in the placebo arm.

[0:25:07]
That was against placebo death in the trial, and the serious adverse events were balanced, but I think it's important to note that that includes a RSV hospitalization, so that includes also the benefits that we are expecting to get from the product, which means assuming that serious adverse events often involves hospitalization, that there is something else that is compensating for the hopeful benefit, and particularly there was some, at least some imbalance in the nervous system, serious adverse events. Now, when I look on the other trial, the Medly trial, which was for babies that were early preterm and babies with comorbidities, again at the ratio of two to one, but this time not against placebo, but against the palivizimab, which is an existing treatment, the imbalance of the deaths continues with five to one.

[0:26:15]
Again, the serious adverse events are balanced, and again, there is an imbalance in the nervous system, serious adverse events, as well as in gastroenteritis cases, and interestingly, two of the babies that died in the Melody trial were from gastroenteritis, and these are healthy babies, which is, based on my discussions with doctors, it's a pretty rare event. And then there is a third trial that is now, has been run in Europe, the Harmony trial in three countries, France, UK, and Germany, that doesn't have any deaths in either one of the arms. Again, it's against placebo, not against placebo, against lack of treatment, so it's an open-label one. Actually, the serious adverse events rates are higher in the immunized, and again, there is a serious imbalance on the nervous system, serious adverse events.

[0:27:11]
By the way, I just want to recall my question yesterday about the more refined quantification of the benefits in terms of number of hospital days, ICU days, and so forth. It turns out that the protocols of all of these three trials do suggest that the vendors have to report on those metrics, and the only thing that I found is an early reporting from the Melody trial that actually suggests that the immunized baby stayed longer in the hospital once they were hospitalized, which could raise the concern of potentially disease, immunization-enhanced disease. Now, if I look on the clinical trials of the product we are supposed to vote on today, this is the CLEF-ROMIVAB, again, a trial of two-to-one with healthy children.

[0:28:08]
There's, again, imbalance on the deaths, seven to three, against the serious adverse events are balanced despite of the fact that they capture also RSV hospitalizations. The nervous system serious adverse events is 25 to four, and the gastroenteritis seems to be 30 to 10, again, imbalanced. And another important point that I think we should think about is that this product is giving a 105 milligram dose. The previous product that was already approved is given either in 50 milligram or two doses of 50, which is 100 milligrams, so it raises the questions about dose relationship here. And it seems that there's also an ongoing trial on the current product, again, with unhealthy children with comorbidities, where the only reporting that I saw so far is from Merck, but it does report on eight to four deaths in the, again, more in the immunized arm.

[0:29:17]
So, when I look on all of this, I would like to hear maybe from our colleagues at the CDC, should we not be concerned that maybe there are some safety, potential safety signals? Now, these are small numbers, so clearly, you cannot establish a safety signal based on that, but should we be concerned? And when I considered the post-marketing analysis we've seen yesterday, which was, by the way, well done, very, very nice analysis, but focused on very specific adverse events and on a very short period of time after the immunization, and does not consider death. So, I just want to ask both my colleagues in the committee, but also the CDC colleagues here, should we perhaps be concerned that there are side-by-side to the benefits, alongside the benefits, we also have some things that you should be concerned about.
[Martin Kulldorff]

[0:30:15]
So, thank you. Sorry for taking a long time. Thank you for those comments.

CDC and Merck Response to Safety Concerns

Is anybody from the CDC who would like to respond?
[Danielle Mulya]
No, I'm not getting cut off. It's just that now I drink this, and it's a lot. Yes, thank you.
[Vivian Dugan]
I think since these are questions related to the clinical trials, if Merck is on the line and would like to answer the questions about their data.
[Unknown]
We also have a hand in our room, in case you can't see it.
[Robert Malone]

[0:31:00]
You might be muted.
[Anushua Sinha]
Hi, can you guys hear me? I think, this is Merck, can you hear me?
[Vivian Dugan]
Yes, we can hear you now.
[Anushua Sinha]
Good morning, this is Dr. Anushua Sinha. I'm speaking from Merck Research Labs, and thank you for the opportunity to address the question. As was mentioned earlier, clostrovimab is a passive immunization. It's a monoclonal antibody that was recently licensed by the US FDA and indicated for the prevention of RSV disease in infants as they're entering their first RSV season. The review by FDA was extensive and included both our safety and efficacy data. And as has been provided to the ACIP working group, during their deliberations in November last year, we've provided extensive materials concerning the topic under discussion.

[0:32:02]
It's important to note that throughout our clinical trial conduct, there was extensive analysis of these events. And importantly, none of these events were deemed by investigators to be associated with RSV or with the interventions given to the infants. Another important point is that there were no trends identified. I'm sorry, there's some background noise. Can you guys still hear me?
[Unknown]
We can hear you. For everyone else, please mute your microphone.
[Anushua Sinha]
Yeah, so I'll just roll back a little bit from when the background noise started. So importantly, each of these events was evaluated by the investigators, and none were deemed related to either RSV or the intervention administered to the child. No trends were identified in terms of cause, system organ class, clustering in terms of time.

[0:33:06]
That means there was no temporal trend either. And I do want to emphasize that the first trial mentioned, the Healthy Infant Trial, that's Protocol 4, also called CLEVR, was randomized 2 to 1. So when counting events, one must be aware of that 2 to 1 randomization. Thank you.
[Martin Kulldorff]
Thank you very much.

CDC Presentation on RSV Death Data

Okay, Brianna Barnes, please.
[Danielle Mulya]
Hi, could we pull up slide 53 from the ETR deck? This is Danielle Mulya from the Maternal Pediatric RSV work. We have a slide prepared for this question.
[Unknown]

[0:34:05]
Sorry, are you able to hear me? Yes, we're pulling it up.
[Danielle Mulya]
Thank you. I guess I will say sort of while it's being pulled up. So we did evaluate deaths as a potential harm for clostridomab. As Dr. Sinha mentioned, these were measured in the 365 days post-immunization of the clostridomab pivotal phase 2b3 trial. They were balanced between groups, between the clostridomab and the placebo arm, because if you note, the study design was 2 to 1 to the intervention. So while there were 7 events in the clostridomab arm and 3 events in the placebo arm, this is what we would expect if we randomized 2 to 1.

[0:35:01]
There was no pattern observed in cause or timing of death related to the intervention. And I actually think we can turn it to FDA to comment more on their safety review of this product.

FDA CDER Comment on Safety Review

[Tracy Beth Hogue]
I didn't know if you wanted me to comment as the ex-officio. But so I did want to mention that this product was approved by CDER. And so I, as ex-officio, I actually, I work in CBER. And so I would like to take, be able to take the opportunity to get a comment from CDER, rather than comment on their behalf about the review, if that would be acceptable.
[Martin Kulldorff]
Is there anybody from CDER, FDA CDER, on the call?
[Amy Hodewanek]
Again, answer. Hi. Hello. Can you hear me?
[Martin Kulldorff]
Yes.
[Amy Hodewanek]
Hi, this is Amy Hodewanek from the Division of Antivirals in CDER. I don't have much to add beyond Merck's summary, but I will say that we did review all of these narratives very carefully.

[0:36:06]
And we did not observe any trends or clusterings and causes of death, and nothing that seemed suggestive of a drug-related cause of death in any of these cases. And similarly, as has been pointed out, this is a monoclonal antibody. And generally, this class is well tolerated with limited toxicity.
[Martin Kulldorff]
Thank you so much, Dr. Limay.
[Retef Levy]
Thank you for the responses.

Further Discussion on Safety Trends Across Trials

I think I acknowledge the two-to-one ratio of the tribe. But I think that one trend I would like to ask you about is that you have here five, sorry, four trials. In all of them, the numbers of the deaths are going in one direction. So, wouldn't that be some kind of a trend that we need to think about?

[0:37:03]
Because I understand also, and I think we agree, these trials are very small. They are not powered to actually detect a lot of signals unless they are very, very strong. But when you look on four different trials and you see the same patterns or similar patterns, doesn't it tell us something of two very similar products, right? So, I'm just curious to hear your thoughts about this. Thank you.
[Martin Kulldorff]
So, if there's no response from FDA, CDER. So, these four trials…
[Amy Hodewanek]
Hello, this is…
[Martin Kulldorff]
Please go ahead.
[Amy Hodewanek]
This is Amy again from CDER. I wasn't sure if that was directed to us necessarily or to the company directly. But, you know, yes, it does…the numerical numbers go the wrong direction in these studies.

[0:38:02]
But if you look at the percentages here, I mean, it's 0.3 versus 0.2 percent. I mean, we would not consider that to really be a difference in the death rate between the two arms. These are very small numbers. And so, we did not find that to be any sort of meaningful trend or difference between arms. And again, we put a lot of weight in our review of the narratives for these cases and looking at potential biological plausibility in terms of the causes of death and the receipt of clozrovimab.
[Martin Kulldorff]
So, this is Martin Kulldorff. So, I have a comment. So, in these four trials, I think three of them are for the neosibimab, which has already been recommended by ACIP in a previous meeting, which we are not making a vote on. There, there was actually more of an imbalance, and I think it's critically important to monitor that as we move forward about the mortality and other adverse, potential adverse reactions to neosibimab.

[0:39:02]
But we're not voting on that product right now. So, we're voting on clozrovimab, and excuse me for not always pronouncing these things correctly. And I think for that, the mortality was actually quite balanced, as we can show on the slide here. So, it could be potentially that this new product that was just recently approved by FDA, it could even be that it is superior to the neosibimab that's all been recommended. But we don't know that. So, that's something that would have to be looked at, and it's important, I think, to look at as we go through this next season of these products.
[Retef Levy]
Dr. Levine? Yeah, I just want to clarify that my understanding is correct. So, is there an ongoing trial now for clozrovimab that the current reporting is eight deaths versus four between the immunized and the non-immunized, the ones that get the standard care?

[0:40:06]
Is that a fair understanding on my part?
[Amy Hodewanek]
This is Amy from CDER again. I would defer to Merck to provide an update on ongoing or recently completed trials. Thank you.
[Martin Kulldorff]
This question is directed to Merck. If you can respond, please.
[Anushua Sinha]

[0:41:06]
Hello, this is Merck again. Can you hear me?
[Martin Kulldorff]
Yes, thank you.
[Anushua Sinha]
It's Dr. Sinha from Merck Research Labs. Indeed, in addition to the Healthy Infants Study Protocol 4, also known as CLEVR that you're looking at on the slide here, we have an ongoing trial in at-risk infants. That's Protocol 7. It also goes by SMART. And in that study, infants are randomized one-to-one to receive either clozrovimab or palovizumab. We did an interim analysis to support our FDA licensure. And in that interim analysis, as you've noted, there were eight deaths in the clozrovimab arm and four in the placebo, sorry, excuse me, palovizumab arm. Each of those deaths was extensively analyzed and was under review by our independent external data monitoring committee.

[0:42:04]
As noted, with the Healthy Infant Trial Protocol 4 that we reviewed earlier, there was no death that was deemed associated with a study intervention. There was no clustering in terms of causality, system organ class, or time of event, that is to say temporality. And as noted by other speakers, these events are rare, and the study is ongoing. This was an interim analysis. Thank you.
[Martin Kulldorff]
Thank you for that.

Dr. Meissner's Comments on RSV Safety and Efficacy

I would also like to know if Dr. Meissner have any comments on this or thoughts. Dr. Meissner has been a member of the working group on RSV and continue to be.
[Cody Meissner]
Thank you, Dr. Kulldorf. These are all issues that were extensively discussed in our work group, which included over 60 members.

[0:43:14]
We went through the details very, very carefully. And I think I appreciate Dr. Retsev's careful review of the records, but the work group is comfortable with the results from the different Clastrovimab trials. I will say that studies in high-risk infants, including preterm infants, that's a very fragile group, and unexpected deaths unfortunately occur in both groups.

[0:44:07]
I don't believe there was any evidence, as has been stated, that there was an imbalance or any pattern associated with adverse events, serious adverse events among the Clastrovimab recipients. I think that the work group was very comfortable making the recommendation that they did.
[Martin Kulldorff]
Thank you so much for that.

Acknowledging the RSV Working Group and Committee Members

And I also want to take this opportunity to, one, really thanks the work group who's been, and that's not just Dr. Meissner, many other people in the work group has worked very, very hard on this. I would also really like to thank my fellow members of this committee, because in the presentation yesterday, it was mostly about the maternal vaccine and the NeoCivimab, which has already been recommended by a previous ACIP meeting.

[0:45:14]
But the members of this working group has sort of gone beyond that information that was presented yesterday to also look in very great detail at the Clastrovimab, which is the thing that we are voting on today, and that was just recently approved by FDA two weeks ago. So, I really want to commend my fellow members of this committee for stepping in and do, and really examining this very, very thoroughly.

Open Floor for Ex Officio Members and Liaisons

And also, if there's any other ex officio members or liaisons to this committee who wants to comment, can you please do so by raising your hand, and then we can have you also comment.
[Robert Malone]

[0:46:13]
Dr. Malone. I'd just like to say that there's been very, very active discussion and consideration within the committee, just for the record, concerning this product. It has been very actively debated internally, and I'm satisfied that given the short period of time we have to address this, that I'm comfortable that we have sufficient information, and the committee itself has rigorously, to the best of its ability, considered these various aspects and has had an opportunity, despite the short time frame,

[0:47:06]
to investigate and discuss and also be briefed on the underlying issues in science. Over. Thank you. Are there any requests for comments from?
[Martin Kulldorff]
Okay, so we have one. Robert Hopkins, please.

Public Comment on RSV from National Foundation for Infectious Diseases

[Neil Patel]
Good morning. This is Dr. Robert Hopkins from the National Foundation for Infectious Diseases. RSV is the leading cause of infant hospitalizations in the U.S. The scientific evidence and data clearly support the use of maternal RSV vaccines during pregnancy, as well as monoclonal antibodies to help protect infants born to mothers who are not vaccinated during pregnancy.

[0:48:03]
NFID urges ACIP to ensure that any changes made to RSV recommendations are evidence-based. We remain committed to protecting infants from serious RSV-related outcomes. Thank you.
[Martin Kulldorff]
Thank you so much. So, I think we are ready to proceed to Dr. Levine.
[Retef Levy]
Yeah, one sentence.

Dr. Levy's Personal Perspective on RSV Vaccination

I'm a scientist, but I'm also a father of six kids, six children, and I think it's also important to put yourself in the shoes of a parent. So, I'm trying – one of the things that makes me kind of beyond the science, the data, I was asking myself, what if I would be just a young parent for a baby? And I had the amazing opportunity to be in that situation six times. And I know all the information. How would I think about this dilemma? And I think if I had a baby that was born early or had, God forbid, some underlying conditions, knowing the threat that RSV can pose to a baby like that, I would probably use these products to protect my child from this disease, because it could actually cause deaths to the baby.

[0:49:27]
On the other hand, if I was the father – and luckily, I was the father of a healthy child that was born on time – knowing all of this, I would be concerned to use that. And I think that – I understand that we're trying to reduce the burden of hospitalizations, and these are all very important metrics. But I think we also need to ask ourselves, what a parent would say given this data?

[0:50:00]
And I think that most parents that have a healthy baby would be concerned to use a new product against the disease that has turned out in the past to be quite tricky against immunization and vaccination. I think they would be concerned. And as a father, I can feel that I would be concerned.
[Martin Kulldorff]
I just wanted to share that. Thank you. Thank you for that. And we have Dr. Pepsworth, who is a member of the committee.

Dr. Pebsworth's Questions on Safety Data and Co-administration

[Vicky Pebsworth]
Hi. You know, I would like to see again the safety and effectiveness outcomes data that are broken out by infant health status, especially gestational age. So, I would just like to understand the difference between the health outcomes of, you know, very sick infants and healthy children. The other comment I have is, do we have data on effectiveness and particularly safety when this product is given within the context of the current schedule?

[0:51:13]
Because depending on when the product is given, it could also be given with several vaccines, including hepatitis B, rotavirus, DTaP, Hib, pneumococcal, polio, COVID, and flu. So, do we have information on simultaneous administration with these other products as it relates to safety outcomes? Thank you.
[Martin Kulldorff]
That's a very important question.

Response to Questions on Safety Data and Co-administration

And I think the working group have looked at that. Could you address that, Dr. Meissner?
[Cody Meissner]
Yes, I'd be delighted to address that, Dr. Caldor. First of all, this, and it's a question of how far we want to go in this discussion.

[0:52:01]
But remember, approximately 80% of the children who are hospitalized for RSV, which is approximately 2% to 3% of the birth cohort, are perfectly healthy children who don't have prematurity, who do not have congenital heart disease, chronic lung disease. These are infants who almost invariably become symptomatic with their RSV infection. Approximately a third of RSV-infected children have lower respiratory tract infections, which necessitates visits to their pediatrician's office or to the emergency department, even if they're not admitted. So, we cannot identify who among those 80% are the children who are going to experience severe lower respiratory tract disease.

[0:53:06]
Clearly, there are factors. People are looking at that aggressively. But we cannot identify who is most likely to benefit from administration of clostrofimab or nircefimab. The second point is death is very rare in the United States among infants due to RSV. There are probably fewer than 100 deaths a year in the United States due to RSV in very young children. Those are primarily occurring in children who have other comorbidities, which I just mentioned. As people have noted, it would be nice if we could use death as an endpoint, but there aren't many deaths, so it's not possible to do that.

[0:54:04]
So, the best primary endpoint that can be established is hospitalization rates. We can also look at rates of ICU admission. But the data is consistently demonstrating that these vaccines, and they're really not a vaccine as we know. I think that's why there's confusion. These are monoclonal antibodies that are passively administered. They're not a vaccine. It's not an antigen, which stimulates the host's immune response. We haven't talked about maternal vaccination. If a woman decides that she does not want to receive an RSV vaccine during gestation, between 32 and 36 weeks at the time of the year when it's most beneficial, then the alternative is to administer a monoclonal antibody to the infant at birth.

[0:55:16]
My response to RETSEP is that, Dr. Oliva, if I were your pediatrician, I would strongly recommend that your wife either receive the RSV vaccine or a monoclonal antibody at birth. There are various issues that go into that decision-making process, but one or the other should be administered or at least be available to every woman while she is pregnant. And I think that we've come so far in the last few years in making these products available.

[0:56:03]
And again, it's really a result of the extraordinary investigations that Barney Graham has conducted largely under NIH support and his colleague, Jason McClellan, that we've gotten to this point with the monoclonal antibodies and the vaccines. These are truly remarkable products. They are safe and they're effective. And I don't think there's any further data that needs to be presented. These, I think we're in a position, the work group has spent an enormous amount of time, the FDA has spent an enormous effort looking at safety and efficacy, and it is simply not an issue here. Over.
[Martin Kulldorff]

[0:57:01]
Thank you. Dr. Meisner, can you also address the question by Dr. Petzworth about concomitant administration of the monoclonal antibodies at the same day as one of the vaccines in the shuttle schedule? Because I think the work group did look at that.
[Cody Meissner]
Yes, and I will go. Remember, there are there are three monoclonal antibodies. Pellivizumab was the first generation monoclonal antibody that became available, I think, was in 1999. And then clasrovimab and nircevimab are second generation or antibodies. They contain certain the YTE mutation. There are three amino acid substitutions in the FC fragment that prolong the half-life of these monoclonal antibodies so that a single dose is protective throughout the RSV season. With pellivizumab, that was not the case.

[0:58:02]
A dose had to be administered every month for five months to cover those infants during the RSV season. We've advanced far beyond that. And we have a great deal of experience with pellivizumab administration because it's given over a five-month period. And there's absolutely no interference with any of the standard routinely recommended childhood vaccines. So, I'm very comfortable reassuring people that that is not an issue.
[Martin Kulldorff]
Is that? Yes, thank you so much. Thank you so much.

Public Comment on RSV from American College of Physicians

We have a comment or question by Jason Goldman. Dr. Goldman, please.
[Jason Goldman]
Thank you. Jason Goldman, American College of Physicians, speaking as an individual. Dr. Meisner said much of what I was going to bring up, so thank you for those eloquent comments.

[0:59:01]
I just want to reflect that as physicians who actually take care of patients, the medical doctors, the clinicians, we see the effects of disease and if they are untreated and not prevented. And certainly, those who are healthy get sick. And that is not a sole criteria for saying something does not work, that it is only given to those who are at risk. Because we do not know our risk until we actually experience the disease. So, healthy children do get RSV, do get sick, and some end up hospitalized or even die. So, it is important to approve this very important intervention, which is not a vaccine, but is passive immunity. And as a father of two children, I wish they had this when they were born. This is a tremendous advance for medical science. And I urge the committee to approve and pass this resolution so that we can continue to protect our children and keep them healthy.
[Martin Kulldorff]

[1:00:05]
Thank you. Thank you, Dr. Goldman.

CDC Response on Co-administration Safety Data

And we have Dr. Sarah Meier from the CDC.
[Vivian Dugan]
Hello. Yes, I wanted to return to Dr. Pemsworth's question about co-administration. We do have real-world evidence from the vaccine safety data link that Dr. Daley presented yesterday. A very high proportion of those infants had received simultaneous vaccination with another vaccine. And I'll turn it over to Dr. Daley to go through those details from our real-world data.
[Robert Malone]
Thank you, Dr. Malone. This is for Dr. Meissner.
[Vivian Dugan]
Oh, sorry. I was trying to tag Dr. Daley if he would like to add more details.
[Robert Malone]
Oh, okay. Sorry.
[Martin Kulldorff]
My fault. Thank you.
[Matt Daley]
So, this is Matt Daley. Can you hear me okay, Dr. Koldner?
[Martin Kulldorff]
Yes.
[Matt Daley]
So, the nursivumab safety evidence that we presented yesterday was in 74,000 infants exposed to nursivumab.

[1:01:04]
And so, that's roughly 20 times the size of the original clinical trial or more. And that's in routine practice. And so, as I summarized in the slides yesterday, 20% of the neonate cohort received same-day hepatitis B and 84% of that older age group received simultaneous same-day vaccination with routine vaccines. And so, essentially, the safety evidence that I presented yesterday, in particular for that group who were 37 days to less than eight months of age, does represent safety with simultaneous vaccination. Over.
[Robert Malone]
Thank you. Dr. Malone.

Discussion on Potential Age Shifting of RSV Disease

One of the concerns that I've heard raised by colleagues in the medical community, primary care providers, is that with these products, we may be merely delaying the potential for disease in this population to the following year.

[1:02:06]
So, year two of birth rather than year one. Dr. Meissner shared with me a current understanding of the pathophysiology. I'm asking Dr. Meissner, can you address this issue of the terminal micro airways and the implications for this product and state of development of the child? Over.
[Cody Meissner]
Yes. Thank you, Dr. Malone. Just very succinctly, um, the most severe RSV disease we see is in children in the first 90 days of life. Those are the children most likely to be hospitalized. And the reason that they're at increased risk is because they're bronchioles. That is the little air tubes that conduct air into the alveoli, the small pockets in the lung where, where carbon dioxide and oxygen are exchanged, become inflamed with an RSV, lower respiratory tract infection.

[1:03:15]
That, uh, inflammation is enough to completely occlude their airways because they're so narrow in diameter in a very young child, particularly a preterm child. By the time a child reaches the second year of life and beyond those airways are larger. And so a small amount of inflammation in, um, the airway in a child in the second, third, fourth, fifth, uh, year of life is much less likely to result in the same degree of respiratory distress that a newborn might experience.

[1:04:03]
So really the monoclonal antibody for healthy children is given to prevent the infection from occurring at the highest risk period. That is the first 90 days. Now, one of the questions that's been asked and I believe has been answered is that these monoclonal antibodies still enable a child to be infected, but the child does not get lower respiratory tract infection. And so the child builds up immunity against RSV and that may very well protect him or her in the second year of life. And, um, even if it does shift the RSV infection, if there is age shifting to the second year of life, it's not as problematic because again, the airways are larger in diameter and can tolerate a small degree of inflammation that occludes the lumen of the airway.
[Martin Kulldorff]

[1:05:12]
Over. Thank you very much. And I think we're going to proceed, uh, to the voting.

Proposed Vote on Clostrovimab Recommendation

So the draft vote is, uh, uh, ACIP recommends, uh, and there's actually two of them. The first one is ACIP recommends infants ages less than eight months born during or entering their first RSV season who are not protected by maternal vaccination, receive one dose of clastrovimab. And I want to just clarify that this is not in addition to, uh, the, uh, uh, the neosemimab, which has already been recommended. So it's basically that the child will receive either, uh, either the clastrovimab or nesrevimab or the mother would have received the vaccination during pregnancy.

[1:06:01]
So there's one of these three should be done. It's not in addition to that. It's an instead of, uh, do we have a motion for this, uh, uh, Dr. Malone?

Motion and Vote on Clostrovimab Recommendation

[Robert Malone]
I move for approval of this, uh, draft recommendation language. Over. Thank you.
[Martin Kulldorff]
And do we have a second? Yes, I second. Okay. We have a second. So let's vote then. And, uh, why don't we start with, uh, Dr. Malone. I vote yes. Dr. Hebron? I vote yes. Dr. Pagano? Yes. Dr. Levy? I vote no.
[Retef Levy]
I just want to clarify that, um, my objection is based on the fact that I don't feel this is, uh, ready to be administered to all healthy babies. I think we should take a more precautionary approach to this. Um, but I respect the discussion and my, the opinions of my colleagues.

[1:07:03]
I, I vote no. Thank you.
[Martin Kulldorff]
Thank you. Uh, Dr. Meissner? Yes. Dr. Petchworth?
[Vicky Pebsworth]
I vote no.
[Martin Kulldorff]
And, um, um, as, um, I, I'm already going to vote yes. So we have, uh, uh, five votes for yes and two votes for no.

Proposed Vote on Vaccines for Children Resolution for RSV

Um, um, and we also have a second draft vote, which is, and this was presented yesterday at the meeting, approve the updated vaccines for children resolution for prevention of RSV.

Discussion on VFC Resolution and Equity

Uh, so, um, we'll do the same order. Dr. Malone?
[Robert Malone]
Hmm. Uh, um, I wasn't aware that we were going to have this vote.
[Martin Kulldorff]
It is essentially the same vote. It's just making sure that this product is available in the vaccine for children's program.

[1:08:01]
That is my understanding. Is that correct?
[Robert Malone]
Yeah. So can, can I hear the actual language that I would be voting on?
[Pedro Folagatti]
We'll need to pull up the, the resolution language. I think if, um, we can go to slide.
[Cody Meissner]
Dr. Kulldorf, can I make a comment?
[Martin Kulldorff]
Please do.
[Cody Meissner]
Um, and, and I, and I appreciate, uh, Dr. Malone's questions. This is extremely important that VFC cover this product. It is very important to ensure equity, uh, in our country so that all children have access to these monoclonal antibodies.

[1:09:07]
It would not be right because these are expensive products that, uh, only well-insured, uh, children or in families that are well-insured have access, uh, to this product. Um, I think, I think we've, we've all discussed the fact that this is, uh, an effective, uh, product and I would strongly encourage everyone, uh, to make it available to all children. Yeah.
[Robert Malone]
Uh, Cody, um, I, I just, uh, was surprised because this language was not in our briefing document for, uh, um, uh, approved language for voting, but I saw on the prior screen that was just displayed, um, the, uh, I know, uh, my, my confusion is resolved because the issue here is, uh, just the nuance of similar approval, but specifically for the VFC program, if I'm understanding correctly.

[1:10:08]
Is that the case?
[Unknown]
I, I can clarify.
[Pedro Folagatti]
So typically after a, a vote occurs, um, on the recommended, uh, product, then there is a resolution by the committee to add that to the formulary for the VFC program.
[Robert Malone]
Thank you for the clarification. Uh, Malone votes yes. We'll hold on a little bit. Uh, Dr. Daskalakis.
[Unknown]
Uh, totally just a point of order. I'm not sure if we necessarily have a motion to approve and a second on this vote yet. So you may want to do that as well. Okay. Malone, uh. One other comment is also about 50 percent of American children get their vaccines, um, and immunizations through VFC.
[Robert Malone]
Yeah.
[Unknown]
So, um, that's the background.
[Robert Malone]
Yeah, yeah. Thank you.

Motion and Vote on VFC Resolution for RSV

Yeah. Uh, Malone, Malone moves. Okay. I second.
[Martin Kulldorff]

[1:11:00]
Uh, while voting, can you please state your name, uh, whether you have conflict of interest, and then you vote. Malone votes yes. And do you have a conflict of interest?
[Joseph Hebelin]
No conflict of interest. Thank you. Dr. Hibblen. Dr. Hibblen first appreciates the clarification. Secondly, I vote yes. Third, I have no conflicts of interest. Dr. Pagano. I vote yes and no complications, no contradictions. And you have a name?
[Martin Kulldorff]
James Pagano. Dr. Lela. Reza Flevi.
[Retef Levy]
I don't have any conflicts of, uh, conflicts of interest. I, I think that we need to ensure access. So, whatever kids need to actually use that product, of course, I think we need to make sure that they get it. So, yes.
[Martin Kulldorff]
Dr. Meissner.
[Cody Meissner]
Coding Light. Meissner, uh, votes yes, and I have no conflicts.
[Martin Kulldorff]
Dr. Papsworth.
[Karen Reed]

[1:12:00]
Sorry.
[Vicky Pebsworth]
Sorry. I vote, uh, yes, and I believe that I am required to read a statement. I don't know, um, whether I have a conflict or not, but, um, it says as required under the ACIP policies and procedures. I'm also disclosing that I own shares in the healthcare sector fund that includes holdings relative, relevant to the ACIP, including vaccine manufacturers. However, the amount of that shareholding, it's under the Office of Government Ethics Regulatory de minimis amount. I understand that I, therefore, can fully participate in the ACIP meeting.
[Martin Kulldorff]
Thank you. Can you state your name?
[Vicky Pebsworth]
Vicky Papsworth.
[Martin Kulldorff]
Thank you. My name is Martin Kulldorff. I have no conflict of interest, and I vote yes.

[1:13:02]
So, we have a vote of seven to zero on this.

Acknowledging the Working Group and Committee's Work

So, thank you, and again, I really want to stress, uh, thank you very much for the working group, for the enormously thorough work you've done. Thank you for the CDC staff, and especially thank you for my fellow members of this group who, at very short, uh, notice, have really emerged yourself into this issue, uh, of, uh, cluster roadmap, uh, and, uh, it was only approved by FDA, uh, I think 16 days ago. So, uh, uh, there was a very short time to, uh, to very quickly, uh, uh, get all the information that was needed, uh, both, uh, presentations yesterday, but also a lot of information in addition to this. So, thank you so much.

Call for Continued Post-Market Safety Surveillance

[Cody Meissner]
Dr. Kulldorff, can I make one comment?

[1:14:02]
I would just like to recognize the contributions of Jefferson Jones, who has led, uh, the, uh, work group throughout this procedure, and has just, uh, done an exemplary job.
[Martin Kulldorff]
Over. Uh, thank you, and I should also stress that, uh, the votes indicate that the recommendations are approved. So, thank you very much. So, I, I just want to, um, encourage, um, our CDC colleagues to, um, we have post-marketing, uh, data now.
[Retef Levy]
I think we should hopefully see, um, soon analysis on, uh, regarding deaths and, uh, and more broad kind of analysis on broader set of, uh, potential adverse events. Again, I think we want to make sure that alongside the benefits, we understand the risks, um, regardless of the decisions of whether to use it or not. We need to have transparency about what it, what is the trade-off here, and I think that the analysis yesterday was very, very well done, but limited to certain, uh, periods of time and certain, uh, specific adverse events.

[1:15:11]
I think we need to hopefully expand that. Thank you.
[Martin Kulldorff]
Uh, thank you, and, uh, post-market safety surveillance is incredibly important, uh, for all vaccines. This is not a vaccine, it's a monoclonal antibody. Uh, it's equally important for, uh, to do the post-market surveillance, safety surveillance for, for not only the, uh, the Cas Rovimab, but also to continue the, uh, uh, safety surveillance for Nersimimab, uh, that has already been recommended previously. So, thank you so much. I appreciate that, um, and, uh, uh, we will now continue to the next item, which is, uh, influenza vaccines, um, and the first, uh, presentation, the introduction is by Dr. Lyle Peterson at CDC.

Transition to Influenza Vaccines Session

[1:16:05]
So, thank you.

Introduction to Influenza Session

[Vivian Dugan]
Okay, so, um.
[Martin Kulldorff]
Oh, sorry. I think the introduction is, uh, I got the name wrong, but the introduction is by Vivian Dugan. I'm very sorry. My apologies.
[Vivian Dugan]
No problem. Good morning, everyone. I'm, uh, Dr. Vivian Dugan. I am the director of the Influenza Division here at CDC. Um, just briefly to review our.
[Martin Kulldorff]
Can you put the microphone a little bit closer?
[Vivian Dugan]
Sure. Thank you. No problem. How's that? Is that better? Okay. Great. So, thank you. Okay. Yes. Thanks. So, good morning, everyone. I'm Dr. Vivian Dugan. I'm the director of the Influenza Division at CDC. I'll give a brief review of the presentations in the influenza session. So, we are going to have five presentations. The first is a presentation on flu block in older children and adolescents, immunogenicity, and safety presented by Dr. Pedro Folagatti from Sanofi Pastor.

[1:17:05]
Next slide, please. And then I will give, uh, presentations on the next two topics. That's estimates of influenza burden and burden averted through vaccination, and then a brief 2024-2025 season update and the proposed seasonal influenza vaccine recommendations for the 25-26 U.S. influenza season. Then we'll have a presentation regarding thimerosal and vaccines by Lynn Redwood, RN, MSN, and finally, proposed recommendations regarding thimerosal and vaccines by Dr. Martin Kaldorf. Thank you, and back over to the chair for the next presentation.
[Martin Kulldorff]
Uh, so, we now have a presentation by Dr. Pedro Folagatti, please.

Presentation on FluBlock in Older Children and Adolescents

[1:18:09]
Good morning. Can you hear me okay? Yes.
[Pedro Folagatti]
Okay. So, good morning. I'm Dr. Pedro Folagatti. I'm a global clinical development director at Sanofi, and today, I'm joined by my colleague, Dr. Tinus Meret, North America Medical Head for Influenza and COVID Vaccines. I will be presenting today the results of our phase immunobridging non-inferiority trial of the quadrivalent recombinant influenza vaccine, which is licensed as FluBlock in older children and adolescents compared to adults. Next slide, please. For full disclosure of my conflicts of interest, I am a full-time employee of Sanofi, and I do hold shares in the company. Next slide, please. So, I would like to start by giving some background to the technology behind FluBlock. Recombinant proteins have been established as a proven approach to vaccine development against infectious diseases since the late 80s and have a track record of safety and effectiveness across different pathogens, including hepatitis B, HPV, zoster, COVID-19, and influenza.

[1:19:19]
In the context of influenza vaccines, this technology offers some key advantages. The use of recombinant technology ensures the sequence integrity of flu antigens, consistent with FDA-selected strains for seasonal vaccines. The manufacturing process is independent of egg supply and does not require culture or handling of live influenza viruses. There is no egg adaptation of the flu virus in this process. And finally, the recombinant influenza vaccine does not go through an inactivation step, preserving the native hemagglutinin conformation of the wild-type virus, which is best suited for optimal protective immune responses.

[1:20:05]
Next slide, please. Before I share the results of our pediatric study, I would like to highlight some of the key established clinical evidence we have for FluBlock. In a phase 3 randomized control efficacy trial in adults age 50 years and above, we demonstrated 30 to 43% enhanced protection against virologically confirmed symptomatic influenza disease when compared to a U.S. licensed standard dose inactivated influenza vaccine during a predominantly age 3 and 2 mismatched season. In a phase 3 immunobridging study conducted in adults age 18 to 49 years old, comparing FluBlock with the same U.S. licensed standard dose inactivated vaccine showed non-inferior immune responses to 3 out of 4 strains. The trivalent formulation was first licensed in 2013, followed by approval of the quadrivalent version in 2016 for those age 18 years old and above.

[1:21:10]
And the label has now been updated and approved by the FDA to include children from 9 years of age and older based on the data we're presenting today. There were 38 million doses distributed until last year, with updated figures now amounting to over 43 million doses of FluBlock distributed across the globe as of 31st of January 2025. The vaccine has an established safety profile, is well tolerated, with no safety signals identified to date. Next slide, please. So, the study we're presenting today was conducted in the context of our pediatric study and investigational plans for FluBlock that were discussed and agreed with the FDA and international regulatory authorities.

[1:22:00]
I will now provide an overview of the trial design. So, this was a phase 3, multi-center, open-label, and non-randomized immune region study conducted in 36 sites across Spain, Poland, Czech Republic, and the United States. Up to 1,334 healthy children, adolescents, and adults age 9 through 49 years old were planned to be enrolled in the trial. All participants received a single dose of FluBlock. Our primary objective was to demonstrate the non-inferiority of immune responses in the 9 to 17 years old group compared to the immune responses in adults where vaccine efficacy had already been established from previous studies. Immune responses were assessed based on hemagglutination inhibition, antibody titers, and seroconversion rates at four weeks after vaccine administration. And the key secondary objective was to describe the safety profile of FluBlock by age group.

[1:23:04]
Next slide, please. So, this figure on the left represents an outline of the participant's journey in the study. They came for their vaccination visit on day one where a blood sample was drawn at baseline, then had a follow-up safety phone call at day nine, and attended the clinic again at day 29 for a safety review and a second blood draw. Participants were then followed up for six months after the study intervention. Solicited or predefined and actively monitored local injection sites and systemic adverse events were collected for seven days with unsolicited events and magically attended adverse events being collected for 28 days. Serious adverse events and adverse events of special interest were collected throughout the study period. There were two key exclusion criteria that I would like to highlight, and these were the receipt of any other vaccine in the four weeks before or after enrollment, except for COVID vaccines which were allowed at least two weeks before or after the study intervention, and the receipt of any influenza vaccines in the six months preceding enrollment.

[1:24:23]
The last point I would like to cover on the clinical trial design refers to our statistical considerations. Our trial success was based on both geometric mean titer ratios and seroconversion rates at day 29 for each of the four influenza strains. The study was designed with a standard overall 80% power to demonstrate non-inferiority of the immune responses based on eight non-inferiority tests. The statistical criteria to demonstrate non-inferiority for geometric mean titer ratios was that the lower bound of the 95% confidence interval was greater than 0.667, and the lower bound of the 95% confidence interval for the difference in seroconversion rates between the groups had to be greater than minus 10%.

[1:25:18]
Next slide, please. So, here's the participants flow diagram from the 1,334 initially planned. We enrolled 1,308 participants from the 27th of October 2022 to the 1st of May 2023, with 641 participants vaccinated in the 9 to 17 years old group, and 658 participants vaccinated in the 18 to 49 years old group. Of those, 626 children and adolescents and 634 adults provided a pre and a post blood sample for the primary endpoint.

[1:26:03]
Overall, we had high retention rates in this study, which were comparable between the two groups. Next slide, please. Regarding the trial demographics, we had more females than males in this study. The mean age was 13 years in the 9 to 17 years old age group, and 34 years in the 18 to 49 years old group. Volunteers were mostly white, with black or African American participants representing almost 19% of the total enrolled population, and 87% were of non-Hispanic or Latino ethnicity. Next slide, please. Now, I would like to take you through the primary endpoint antibody data. So, again, the objective here is to compare antibody responses at four weeks after vaccine administration between the two age groups.

[1:27:05]
Here on this graph, we have the day 29 geometric mean titers on the y-axis, and the four different influenza strains contained in the vaccine are displayed on the x-axis. The antibody responses for the 9 to 17 years old group are represented in light purple, and the antibody responses in the 18 to 49 years old group is in dark color. The table at the top of the graph is showing the day 29 GMT ratios, with their respective 95% confidence intervals for each of the four strains. The data shows that the antibody responses were comparable between the two age groups, with children and adolescents having relatively higher responses post-vaccine administration compared to adults. This is clearly observed in the ratio of the GMTs, where the lower bounds of the confidence interval is well above the non-inferiority margin of 0.667 for all strains, ranging from 1.09 for BM Agatha to 2.76 for H3N2.

[1:28:16]
Non-inferiority was therefore met for all strains on day 29 GMT ratios. Next slide, please. Now we will look at the seroconversion rates. Seroconversion was defined here by having at least a fourfold increase in antibody titers for those with an HAI titer equal to or greater than 10 at baseline, or a titer of at least 40 in those who were seronegative at baseline. The table here shows the difference in seroconversion rates between the two age groups and their respective 95% confidence interval for each of the four influenza strains.

[1:29:01]
The differences in the percentage of participants with demonstrated seroconversion after vaccine administration between the two groups range from minus 0.59% for H3N2 to 14.3% for BM Agatha. As you can see from the middle column on the table, the lower bounds of the confidence interval was well above the non-inferiority margin of minus 10% for all four strains. Taken together, these data showed that the primary objective of non-inferiority of the immune responses was met for all strains for both day 29 GMT ratios and seroconversion rates. Next slide, please. Moving on to our secondary objective of this study, we had 10 participants, which represents less than 1% of the total enrolled population reporting at least one serious adverse event and 5.1% of participants reporting at least one medically attended adverse event.

[1:30:11]
None of them were determined to be related to this study vaccine by an investigator or the sponsor. No deaths or adverse events of special interest were reported in the trial and there were no substantial differences in the safety profiles between the two age groups. Next slide, please. This slide shows the summary of expected reactions within the first seven days. The data for the 19 to 17 years old group is presented again in light purple and the data for the adults in dark color. The y-axis represents the percentage of participants presenting at least one solicited event and we have data being displayed here for any severity grade and for grade three solicited reactions.

[1:31:03]
As you can see from the graph, we had slightly fewer children and adolescents reporting any solicited adverse event compared to adults. Grade three solicited events overall were reported for 6.5% of children and adolescents and for 4.5% in the 18 to 49 years old group. A similar pattern is observed when we break it down by local injection sites and systemic reactions overall. In this trial, we observed that most of the expected reactions within the first seven days were mild or moderate in nature, had an onset within the first three days of vaccine administration and resolved spontaneously within one to three days. Next slide, please. So here is a summary of the local injection site reactions reported in the study.

[1:32:02]
The x-axis shows the proportion of participants reporting at least one event for each particular reaction. We have mild events shown in green, moderate events in yellow and grade three events in red. As expected, injection site pain was the most frequently reported local adverse reaction in 34.3% of those in the 9 to 17 years old group compared to 40.2% of those in the 18 to 49 years old group. Injection site bruising, swelling, induration and erythema were occasionally reported with no significant differences between the groups. The vast majority of local adverse reactions were mild or moderate in nature. Next slide, please. When we look at the expected systemic reactions, myalgia, malaise and headache were the most frequently reported systemic adverse reactions and these were reported in less than a quarter of participants in both age groups.

[1:33:12]
And less than 3% of children and adolescents reported a febrile episode following vaccine administration. No differences in the profile of solicited systemic reactions were observed between children and adolescents compared to adults. And again, most events were mild or moderate and self-limiting in nature. Next slide, please. Regarding the series adverse events that were reported during the study, seven participants in the 18 to 49 years old age group reported.
[Martin Kulldorff]
Sorry, can you still hear me? We can hear you now. We lost you for a few seconds.

[1:34:02]
Okay, I'll start the slide again if that's okay. Please do.
[Pedro Folagatti]
Regarding the series adverse events that were reported during the study, seven participants in the 18 to 49 years old age group reported nine SAEs and three participants reported four SAEs in the nine to 17 years old age group. None of the events were determined to be related to flu block by either sponsor or investigators based on their assessment of underlying diseases, concomitant therapy, and risk factors. Next slide, please. So, to conclude, flu block elicited robust HAI immune responses in both groups. The primary objective of non-inferiority of immune responses in older children and adolescents compared to adults was met for all four strains on both GMTs and serial conversion rates. The safety profile was comparable between groups, the vaccine was well-tolerated, and no safety concerns were identified.

[1:35:04]
Next slide. This study was funded and sponsored by Sanofi. Next slide, please. Thank you for your attention.

Presentation on 2024-2025 Influenza Burden and Prevented Burden

[Martin Kulldorff]
Thank you for that presentation. Before we do questions and comments, I think we should continue with the next presentation by Dr. Vivian Dugan. Please.
[Vivian Dugan]
Thank you very much. This next presentation will focus on the severity, disease burden, and prevented burden of the 2024-2025 influenza season. As a reminder, these slides are publicly available online at the CDC ACIP meeting website. Next slide, please. The 2024-2025 influenza season in the United States captured really the attention of many media outlets and headlines. You likely have seen reports describing the influenza season as one of the worst in recent history. However, using data to assess the seasonal severity and estimate the disease burden are really essential in providing context to each influenza season, which can be unique and often is.

[1:36:07]
Next slide, please. To evaluate the severity of influenza for the 2024-2025 season, we used three surveillance indicators across all age groups. The graph on the left is the percent of influenza-like illness, which had two peak weeks that were classified as high severity. The middle graph is the rate of influenza hospitalization across all ages, which also had two peak weeks that were classified as high severity. And then the graph on the right is the percent of influenza deaths, which had five peak weeks classified as high severity. So, as shown in these three graphs, the 2024-2025 season for influenza was classified overall as high severity season across all ages and across all indicators. Next slide, please. Looking at influenza severity for this season across all ages and by all age groups, we can compare the 2024-2025 season to that of past seasons.

[1:37:00]
So, when we do that, this season was the first high severity season overall and by age groups since the 2017-2018 season. That's the orange bars at the bottom compared to the 2017-2018 orange bars across the middle. Next slide, please. So, next I'm going to describe our methods for estimating influenza disease burden to understand the population impact, to identify risk groups, and to really describe the impact on health systems. Next slide, please. Data-driven burden estimates for seasonal influenza viruses are necessary because we do not know the exact number of influenza illnesses, hospitalizations, or deaths that occur each year for several reasons. U.S. states are not required to report individual seasonal influenza cases or hospitalizations for people of any age. However, states are only required to report deaths for children younger than 18 years. Surveillance systems and healthcare settings cannot capture all influenza virus infections.

[1:38:01]
In fact, many people who become sick with influenza may not seek medical care, and even those who do seek care may not be tested. People may seek medical care later in their illness when influenza can no longer be detected from respiratory specimens. And influenza symptoms are nonspecific, so individuals can be misdiagnosed with a different respiratory illness. So, for these reasons, public health officials rely on influenza burden estimation and severity assessment from real-world data to understand the population impact, to identify risk groups, to describe the impact on health systems, to inform policy decisions and communication messages, and to inform economic burden and cost-benefit studies. Next slide, please. Influenza disease burden is described by clinical diseases ranging in severity from symptomatic illnesses to medically attended illnesses, hospitalizations, and deaths. Estimations are routinely completed for five age groups shown there on the left, zero to four years, five to 17 years, 18 to 49 years, 50 to 64 years, and 65 years and older.

[1:39:04]
In the United States, we estimate the influenza disease burden during the season and annually at the conclusion of each season. These estimates rely on multiple data sources, and estimates are not considered final until approximately two years following the conclusion of the season, as that is when all the necessary data for that season becomes available. Next slide, please. To estimate the disease burden for influenza, we use a multiplier modeling approach. In step one, shown there in the middle of the slide, the influenza-associated hospitalization rate from a routine sentinel surveillance system for patients hospitalized with laboratory-confirmed influenza is multiplied by an adjustment factor for testing practices, and then multiplied by the population. This adjustment factor uses survey data on the probability of one being tested for flu, and then also the sensitivity of the test diagnostic being used. In step two, deaths are calculated by multiplying the hospitalizations by a ratio of death to hospitalization, and then multiplied by the population.

[1:40:04]
In step three, the symptomatic illnesses are obtained by multiplying the hospitalizations by a ratio of the number of cases for every hospitalization. And finally, in step four, the number of outpatient medical visits is calculated by multiplying the number of symptomatic illnesses by the probability of seeking medical care when ill, and that's obtained from a telephone survey of healthcare-seeking behavior during an influenza-like illness. Estimates presented today will not include deaths. Our death estimates will be available once data collection for hospitalization outcomes is complete, likely towards the end of September of 2025. Next slide, please. So, this is our preliminary 2024-2025 influenza disease burden estimates for symptomatic illnesses, medical visits, and hospitalizations by age groups. The greatest number of symptomatic illnesses and medical visits were among those 18 to 49 years, but age 65 years and older had the highest number of hospitalizations.

[1:41:01]
Next slide, please. When comparing this 2024-2025 season to past seasons, all three burden outcomes presented here are higher than any past season during, using this methodology. These estimates are still preliminary and could change as data specific to the 2024-2025 season become complete, but the influenza disease burden on the population during the season was high. Next slide, please. We also estimate the vaccine-prevented influenza disease burden. This quantifies the benefit of influenza vaccination in preventing burden outcomes, informing communication messages around influenza vaccination, and it also identifies where improvement in influenza vaccine uptake and vaccine effectiveness could result in more public health benefits. Next slide, please. So, similar to the disease burden models, the influenza vaccine-prevented disease burden models utilize additional data to produce estimates. Several components of the disease burden models, including the number of illnesses, medical visits, and hospitalizations for each age group are used in conjunction with information on vaccine coverage and vaccine effectiveness in these models.

[1:42:09]
Additionally, we use both vaccine effectiveness against outpatient medical visits, and that's to estimate prevented illnesses and medical visits, and also vaccine effectiveness against hospitalization to estimate prevented hospitalizations. And when sufficient data are available for death, we also apply that. Next slide, please. So, to estimate the prevented disease burden, we rely on both the disease burden model reviewed earlier and a compartmental model that incorporates information on vaccine coverage and vaccine effectiveness. To calculate the prevented disease burden, we first apply vaccine coverage and vaccine effectiveness data from the season to the disease burden estimates. This is to estimate the risk of these outcomes to the susceptible population. We then model those risks in a hypothetical population without vaccination. And so, the difference between the observed disease burden estimates from this season and the estimated burden in the absence of vaccination is the prevented burden.

[1:43:06]
Next slide, please. These are the preliminary 2024-2025 prevented disease burden estimates for symptomatic illnesses, medical visits, and hospitalizations by age group. The most symptomatic illnesses were prevented among those aged 18 to 49 years. The most prevented medically attended illnesses were among those aged 18 to 49 years and 50 to 64 years. And the largest benefit of influenza vaccination was observed in the prevention of hospitalizations among those aged 65 years and older. Next slide, please. This slide shows the vaccine prevented disease burden for symptomatic illnesses, medical visits, and hospitalizations by season and the burden of each of these outcomes, which effectively shows the full burden of each influenza by season. When comparing the 2024-2025 season to past seasons, all three of the prevented burden outcomes presented here are higher than any past season using this methodology.

[1:44:06]
These estimates are still preliminary, and again, they may change as data specific to the 2024-2025 season become available. But despite the data being preliminary, these estimates demonstrate the benefits of influenza vaccination in the prevention of illness, medically attended visits, and hospitalizations. And a dashboard with past seasons estimates of disease burden prevented by vaccination is available on CDC's flu burden prevention website, and that link is on that slide. Next slide, please. So, in conclusion, influenza causes significant impacts on healthcare settings and disease burden in the population each season. The 2024-2025 influenza season was classified as having high severity for all ages and by age groups. This is the first high severity season across these groups since the 2017-2018 influenza season. Additionally, the estimated influenza disease burden was the highest in the United States in roughly the last 15 years.

[1:45:05]
Further, influenza vaccines prevented an estimated 240,000 hospitalizations, with most in adults age 65 years or older. Both uptake of the influenza vaccine and the effectiveness in the population likely contributed to preventing the disease from being even more severe. Next slide. And then I'd like to end and thank everyone from CDC and the influenza division and across the agency that supported this work. Over.
[Martin Kulldorff]
Thank you very much.

Proposed Seasonal Influenza Vaccine Recommendations for 2025-2026

Do you want to state the proposed recommendations for 2025-26? And after that, we can do questions and comments. Sure. We can keep going.
[Vivian Dugan]
Okay. Thank you very much. This next presentation is the 2024-2025 influenza seasonal update and the seasonal influenza vaccination recommendations for the 2025-2026 influenza season, so the upcoming season.

[1:46:09]
As a reminder, again, these slides are all publicly available at the CDC ACIP website. Next slide, please. So, this talk is going to have two parts. First, I'm going to provide a 2024-2025 influenza seasonal summary, focusing on the severity of the season in terms of hospitalizations and pediatric deaths. Then I'll review the proposed updates to the seasonal influenza vaccine recommendations for the upcoming 2025-2026 influenza season, and this includes three recent FDA approvals. The influenza vaccine composition for the 2025-2026 season, approval of Flumist, which is the intranasal trivalent live attenuated influenza vaccine for self or caregiver administration, and then the change in age indication for FluVox, a recombinant influenza vaccine from age 18 years and older to nine years and older.

[1:47:00]
Next slide, please. First, I'll review some aspects of the 2024-2025 season. Next slide, please. So, the 2024-2025 season in the U.S. was, again, a high severity season overall that I just mentioned, and also for all age groups, and again, it's the first high severity season since the 2017-2018 season in the U.S. Influenza viruses were the predominant circulating virus type, but influenza B viruses all co-circulated, but at much lower levels. To give you an idea of that breakdown, over 98,000 specimens tested by public health labs. Influenza viruses were represented at over 94%, with influenza A viruses being represented at about 6%. We also saw co-circulation of both influenza A, H1N1, PDM09, and H3N2 viruses. And so, overall, there was a fairly even split of H1N1, PDM09, about 47 to 52%, and then H3N2 as well across the country.

[1:48:02]
Next slide, please. Oh, sorry. Keep going back one. Got ahead of myself there. Thank you. Okay. So, two of the notable indices of severity for this season were influenza-associated hospitalizations and influenza-associated pediatric deaths. With regards to hospitalizations, the 2024-2025 season saw the highest cumulative influenza-associated hospitalization rates since the 2010-2011 season, and that was a cumulative hospitalization rate from October 1 of 2024 through April 30 of 2025, and that was at 128.1 hospitalizations per 100,000 populations. So, for comparison, the cumulative rate for the 2017-2018 season was 102.9 per 100,000, and that's the most recent prior severe season. I'll cover that a little bit more in the next slides. A second feature, again, of the season is the number of influenza-associated pediatric deaths. As of June 14 of this year, 250 influenza-associated pediatric deaths have been reported this season. This is the highest number of pediatric deaths reported in any non-pandemic influenza season since the condition became reportable in 2004.

[1:49:06]
Next slide, please. This slide provides a little more detail concerning influenza-associated hospitalizations. These data are from FluServNet, which tracks laboratory confirmed influenza-associated hospitalizations reported from select counties in 14 U.S. states. These areas include and account for about 9 percent of the U.S. population. As mentioned previously, the cumulative hospitalization rate reached 128.1 per 100,000 in comparison to that 102.9 for the 2017-2018 season. The chart on the right shows the cumulative hospitalization rates by season for seasons from 2010 and 11 through 2024-2025. The one exception that's not listed there is the 2020 and 2021 season. That is not depicted. That was because that season coincided with the early COVID-19 pandemic, and so historically low influenza activity across the U.S. Among the seasons depicted, the rate for the 2024-25 season has surpassed all seasons since 2010-2011.

[1:50:09]
In the chart on the lower left, you can see the cumulative rate for the 2024-25 season broken down by age group. Hospitalization rates were highest among those aged 65 years and older at a rate of 403.4 per 100,000. For the lowest group, those aged 5 through 17 years, the rate was 39.8 per 100,000. Notably, about 16 percent of these patients required intensive care unit admission, and 6 percent required invasive mechanical ventilation. Next slide, please. Next, I'll provide a brief summary of influenza-associated pediatric mortality for the 2024-25 season. An instance of pediatric influenza-associated mortality is defined as a death in a person under 18 years of age which occurred in the setting of a clinically compatible illness with an influenza-positive laboratory test and for which there was no period of complete recovery between illness and death.

[1:51:09]
Influenza- has been nationally notifiable since 2004. So, for the 2024-2025 season thus far, as of June 14th of this year, 250 influenza-associated pediatric deaths have been reported to CDC. All age groups were affected with 0 to 5 months old accounting for 6 percent of deaths, 6 to 23 months for 14 percent of deaths, 2 to 4 years for 18 percent, 5 to 11 years for 36 percent, and then 12 to 17 years for 26 percent. Next slide, please. To summarize additional characteristics of this population, among 250 influenza-associated pediatric deaths reported for the 2024-25 season as of June 14th, 42 percent had no known high-risk underlying medical condition, and 42 percent had a bacterial co-infection of a sterile site.

[1:52:04]
Notably, 89 percent of those eligible for influenza vaccination were not fully vaccinated. This is a higher proportion than the 82 percent of pediatric deaths observed for the 2023-24 season. Again, this 250 deaths reported as of June 14th are the highest number of pediatric deaths reported in any non-pandemic influenza season since influenza-associated pediatric deaths became reportable in 2004. Next slide, please. Next, we'll move into the proposed updates for the seasonal influenza vaccination recommendations for the upcoming 2025-2026 season. Next slide, please. Few changes are proposed to the recommendations for the 2025-26 season. Annual influenza vaccination remains recommended for those age six months and older who do not have contraindications. As previously, no preferential recommendations are made with the exception that high-dose inactivated recombinant and adjuvanted inactivated influenza vaccines are preferentially recommended for persons age 65 years and older when available.

[1:53:08]
Also, all recipients should receive an age-appropriate influenza vaccine. That is one that is approved by FDA for their age, with the exception that solid organ transplant recipients age 18 through 64 years who are receiving immunosuppressive medication regimens may receive either high-dose or adjuvanted inactivated influenza vaccine. That's without preference over other appropriate inactivated or recombinant influenza vaccines. Recommendations concerning timing, vaccine selection, and contraindications and precautions remain the same as previously. Next slide, please. There are three updates for the 2025-26 influenza season, all of which reflect recent FDA approvals. The first is the influenza vaccine composition for the 2025-26 season. The second is the approval of Flumist, the intranasal trivalent live attenuated influenza vaccine for self or caregiver administration. This is presented to ACIP in April of 2025.

[1:54:02]
The third is the change in the approved age indication for Flublok, the trivalent recombinant influenza vaccine from 18 years and older to nine years and older, and the committee heard these data at the beginning of the session. Next slide. With regard to the U.S. influenza vaccine composition for the 2025-26 upcoming season, as was the case this past season, all influenza vaccines marketed in the United States for the 2025-26 season will be trivalent vaccines. That is, they will contain antigens derived from three different influenza viruses, one influenza A H1N1 PDM09 virus, one influenza A H3N2 virus, and one influenza B virus. The U.S. influenza vaccine composition for the 2025-26 season includes an update to the influenza A H3N2 component. FDA has recommended for the A H1N1 component in A Victoria 4897 2022 H1N1 PDM09-like virus for egg-based vaccines, or a Wisconsin 67 2022 H1N1 PDM09-like virus for cell-based and recombinant vaccines.

[1:55:05]
This is the same as last season. For the H3N2 component, an A Croatia 10136RV 2023 H3N2-like virus for egg-based vaccines, or an A District of Columbia 27 2023 H3N2-like virus for cell-based and recombinant vaccines. This is an updated strain. And for the influenza B component, an influenza B Austria 1359417 2021 B Victoria lineage-like virus. This is the same as last season. Next slide, please. Next, FluMist for self or caregiver administration was approved by FDA in September 2024 and was presented to ACIP in April of 2025. It is anticipated to be available for the 2025-26 influenza season. Consumers will be able to order FluMist for delivery for eligible recipients. Screening for eligibility will be performed by an online pharmacy based on ACIP criteria.

[1:56:02]
For recipients who are approved for self-administration, vaccine will be shipped to the address provided by the person ordering. As previously, FluMist is approved for people 2 through 49 years of age. Within this age range, for those who are deemed eligible for delivery, self-administration is approved for persons age 18 through 49 years. For recipients age 2 through 17 years, the vaccine may be administered by a caregiver 18 years of age or older. LAIV-3 will continue to be available for administration by healthcare providers as previously. No changes have been made to recommendations regarding appropriate populations, contraindications, or precautions. Next slide. Lastly, the third update concerns FluBlock. FluBlock received an additional approval by the FDA for ages 9 through 17 years in March of 2025. Previously, FluBlock was approved for ages 18 years and older, so this approval, so with this new approval, the new age indication is 9 years and older. This information has been updated in the table of available U.S. influenza vaccines for 2025-2026 season.

[1:57:07]
Next slide, please. And then finally, these three changes reflect the updates for the 2025-2026 upcoming season. I just want to thank all of the people at CDC, subject matter experts, staff, and public health partners who contributed to the generation and synthesis of these very important data. Over.
[Martin Kulldorff]
Thank you very much for those presentations.

Questions and Comments on Influenza Presentations

And we will now go to questions and comments.
[Joseph Hebelin]
Then we'll start with the voting members of the committee. Please, Dr. Hibblen.

Discussion on Psychiatric Adverse Events in FluBlock Trial

This is Joe Hibblen. I have a brief comment and a question with regards to Dr. Foligati's presentation. And this regards the slide reporting the 13 significant adverse events reported in the study.

[1:58:06]
As a psychiatrist, I am highly sensitive to emergent reports of suicidal ideation and intentional overdoses. And it would, it struck me that of all the possible significant side effects, there's a disproportionate number of reports of major depression, suicidal ideation, in both the 18 to 49 group and the 7, 9 to 17 age group. And I congratulate Sonofil and Dr. Foligati for being alert and reporting psychiatric side effects because, after all, the brain is connected to the head. Not only physically, but also by the immune system. And that we should be exquisitely sensitive to looking at and reporting significant side effects such as suicidal ideation and major depression.

[1:59:11]
I clearly understand that this is not a randomized placebo-controlled trial. And we cannot assess the differences. I do not know as well how it was determined that these are unrelated. I don't know if there was a predisposing evaluation of psychiatric symptoms before the trial and after the trial. And perhaps this is a new emerging field of questions in immunology and vaccines and treatments. I want to be, I want to congratulate Sonofil and Dr. Foligati for identifying these and describing them. And my question is to whether or not the company has any interest or any plans to prospectively evaluate psychiatric conditions, especially suicidal ideation, an overdose, which I think would be a significant side effect worse than getting the flu.

[2:00:24]
Do you have any plans to evaluate these significant adverse events? Thank you.
[Martin Kulldorff]
Who would like to comment? Dr. Duggan?
[Vivian Dugan]
I would defer to Seneby, who hopefully is on the line.
[Martin Kulldorff]
Dr. Foligati?
[Pedro Folagatti]
Thank you for your question. So, the first thing I would like to point out is that these events were classified as unrelated to vaccination.

[2:01:04]
All of these participants with suicidal ideation, they had a past medical history of mental health disorders. We did not specifically screen for mental health illnesses as part of the eligibility criteria in this study. For the vast majority of these events, the investigators identified clear alternative triggers. And all of the SAEs that were observed in this study, we expect them to fall within the expected background rates for the respected age groups. Currently, we don't have any plans other than our standard post-marketing surveillance on safety events.
[Joseph Hebelin]
Thank you for your answer. What concerns me then is to whether or not there was a worsening of suicidal ideation in these patients, or whether it must be that you enrolled patients with suicidal ideation into the trial.

[2:02:15]
Either it preexisted or it was worsening. And so, without a prescreening, I'm not certain how you can be certain of these events being unrelated to the vaccine. Thank you.
[Robert Malone]
Thank you.

Discussion on FluBlock Technology and Microneutralization Data

Next is Dr. Malone. Thank you, Dr. Kulldorff. I just start off by mentioning that I will have the privilege of working with the current influenza subgroup in the future. Look forward to that. I would like to highlight a couple of things in particular relating to the two products that have been mentioned today.

[2:03:07]
Regarding the FluBlock product, this is truly an innovative technology. It involves the use of insect cells to rapidly manufacture the product. This is a cell-based influenza vaccine that represents really a great example of innovative biotechnology, in my opinion. This technology offers key advantages relative to historic influenza vaccine products, in that egg and other cell-based products require adaptation of influenza strains and their antigens to the cell culture or egg culture environment. So you end up with a vaccine product that is, in some cases, potentially clinically significantly different from the actual circulating antigen.

[2:04:07]
Whereas with the FluBlock technology, with baculovirus technology in general, they're able to go straight from sequence to manufactured protein in a much shorter time frame without the need for adaptation. This is a key advantage. The other product that's been highlighted here, this cold-adapted live attenuated influenza vaccine product that MedImmune has prosecuted now for years against great challenges because it doesn't fit into the kind of standard paradigm for influenza, offers significant advantages historically, particularly in the pediatric population for protection. And, of course, it has the huge advantage of being needle-free. And in this case, that advantage is now being extended down to the level that it was originally intended to, that this can be provided at a much greater access and administration by less skilled personnel.

[2:05:17]
So both of these, I think, I just want to congratulate both manufacturers for their commitment to innovation, appropriate innovation, safe innovation, and a well-designed non-inferiority trial. I have a specific question, and the intention here is to highlight a characteristic and address a concern that may be circulating in certain communities. I request Sanofi to address whether or not there are any fetal-derived products used in the manufacturing of Flublok, over.
[Martin Kulldorff]

[2:06:03]
Dr. Fulekati, please.
[Pedro Folagatti]
I would like to defer the question to my colleagues on doubling. Hi. I'm Tinas Murray, Medical Head for Flu and COVID in North America. So there are none of those products.
[Robert Malone]
Thank you. That's a key issue for certain communities in the United States that have religious concerns. And so I wanted to highlight that this product is free of human fetal tissue-derived material. I was wondering, noting that the HAI assay is the accepted correlative protection for influenza historically, but there has been longstanding interest in microneutralization data.

[2:07:03]
Do we have microneutralization data perhaps as an exploratory endpoint in the Flublok product that could be briefly described?
[Pedro Folagatti]
Thank you for your question. For this specific study, we did have a seroneutralization subset. So we had approximately 400 participants who were randomized into this seroneutralization subset, and we obtained results for approximately 363 of them. So 185 in the 9 to 17 years old and approximately 178 in the 18 to 49 years old. And the overall conclusion is that we do see a substantial increase in the seroneutralization responses for both age groups. So again, we didn't observe any differences in the older children and adolescents compared to the adult responses.
[Robert Malone]

[2:08:05]
Again, I congratulate and thank Sanofi for their commitment to influenza vaccination immunology and for sharing those microneutralization data. My next question has to do, is directed more towards the CDC.

Discussion on Influenza Burden Estimation Methods

Historically, there has been an issue about influenza-like illness and a lumping of multiple upper respiratory infections in the projections for burden of disease and reporting on that. My understanding is that the approach that you're currently using for estimating burden of disease does require an actual influenza diagnostic assay and that this is not a lumped measure that would represent aggregate of viral URIs but rather specific to influenza.

[2:09:06]
Can you confirm that?
[Vivian Dugan]
Thank you, Dr. Mullen, for that question. Yes, these estimates are all based off of laboratory-confirmed influenza for burden.
[Robert Malone]
And that was Dr. Duggan who responded to that question, so.

Discussion on Pediatric Deaths and Number Needed to Treat

Second, the 250 pediatric deaths, which is, let's acknowledge is a modest number, fortunately, do we have a number needed to treat regarding the endpoint of death in pediatric cohort?
[Martin Kulldorff]
May I please state the name before?
[Vivian Dugan]
Sorry, thank you. Vivian Duggan, Influenza Division. An endpoint for treatment for pediatric death, I would have to defer to my colleagues in the SME space if they could raise a hand to weigh in on that, please.
[Unknown]

[2:10:01]
There, yeah.
[Karen Reed]
Hi, this is Karen Reed. I'm an epidemiologist in the Influenza Division. We have previously done that calculation. I don't have it handy, but in recent years, we have not. But we can work on that and get back to you.
[Robert Malone]
My understanding is the committee would very much appreciate having reports of a number needed to treat for major endpoints for these vaccine products going forward. The last point has to do with this paradoxical disappearance of influenza during 2020, 2021, and then this, what, there's the appearance of a trend of increasing pressure from influenza severity in the subsequent years. There's multiple ways, multiple hypotheses for why one might see a trend.

Discussion on Paradoxical Disappearance of Influenza During COVID-19 Pandemic

Let's hope that's not the case. Does the CDC have hypotheses that they can share regarding the paradoxical sudden decrease in burden of influenza disease during the first two years of the pandemic?

[2:11:20]
Over.
[Vivian Dugan]
This is Vivian Duggan from CDC. I can start that answer and then defer to my colleagues in the subject matter experts space to expand. But to start, I think the COVID-19 pandemic changed a lot of general behaviors of people overall. And so there was a lot less direct contact, people moving about, people traveling. So that really decreased not just influenza activity and transmission, but a lot of the seasonal respiratory diseases that we tend to see in the viral space each year prior to COVID-19 emerging. So it's hard to rule out and tease out one specific factor that would be responsible for that. But then I can, has everything moved forward and influenza viruses returned back to circulation along with RSV and other respiratory viruses.

[2:12:09]
Really, we saw, you know, this kind of co-circulation of all of these different respiratory viruses. And we plan for all of those each year to track and just keep an eye on and analyze the data from RSV, influenza. You heard RSV yesterday, SARS-CoV-2 and other viruses. So that we're really understanding the trends and some of the dynamics. But they all really remain quite unpredictable. You probably know as a virologist, if you've seen one influenza season, you've seen one influenza season. They can be very unique and unpredictable. The rapid change and the multiple co-circulation of different types, subtypes, and different clades and subclades is often, you know, keeping us on our toes. But any experts from the SME space want to chime in?
[Karen Reed]
I thought you answered it well. Nothing else to add.
[Martin Kulldorff]
Can you state your name?
[Karen Reed]

[2:13:00]
Sorry. This is Carrie Reed again.
[Robert Malone]
Was there a comment? If not, I have one final. Shall I proceed?
[Unknown]
Karen Reed wanted to say something or not? Okay. Okay. I think she was just identifying herself and then said she had no comment. Sorry about that.
[Martin Kulldorff]
Okay. I'm sorry. So please go ahead. Sorry for the confusion here. Go ahead, Dr. Malone.
[Robert Malone]
So last to CDC.

Discussion on Potential Broad-Based Anergy and Increased Severity

Some members of the scientific community have concern that they're coming out of the COVID pandemic, exposure to the virus, exposure to various countermeasures. There may be a pattern of broad-based energy of some type that might contribute to increased severity of influenza disease.

[2:14:07]
I infer this is probably too early, but I encourage that the agency would be sensitive to that hypothesis and provide us the data so that we can that would either support or refute that hypothesis that there is some more broadly population-based process going on, which might lead to more severe upper respiratory virus clinical pressure. Over. Did that make sense? I hope.
[Unknown]
Who would like to respond to that? Okay, Dr. Dasglasses, please. Thank you so much. And thanks for that question.

[2:15:00]
So I'll start by just thanking influenza division and Dr. Dugan for a great presentation and for that great question. So I think from the perspective of the systems that CDC has to monitor influenza, that may end up being a better question for folks that are doing more pathogenesis-based research. So potentially thinking about maybe if NIH potentially has an idea around that as well. Thank you.
[Martin Kulldorff]
Thank you.

Further Questions and Comments on Influenza Presentations

We'll move forward to Dr. Cody Meissner.
[Cody Meissner]
Thank you very much, Dr. Kulldorff. And I would also want to acknowledge the very helpful presentation by Dr. Dugan and Dr. Foligati. I have questions and comments from both of you, if I may. I'd like to start with Dr. Foligati since he was first in his discussion about flu block. First question I have is, why did you select nine years of age as the lower end of age population for your comparative study with the 18 to 49-year-old?

[2:16:16]
And because I would hope that you could go lower than nine years. I assume it was because at less than nine years, two doses of the vaccine is recommended for children in that category. And I'm just going to list my questions and you can take your pick as to what you would like to address. Um, secondly, so the FDA has approved this vaccine based not on an efficacy trial, but on a seroconversion trial, which is the standard for influenza vaccines.

[2:17:00]
But the question I have regarding that is, was there any impact from the baseline serologic status in children starting at nine years of age on their response to flu block? Number two, number three, there was a better immune response consistently among the nine to 17-year-old subjects than among the older individuals, except for Yamagata B, which is fine because B Yamagata is no longer in any of the vaccines. And which also made me wonder why you presented data using a tetravalent vaccine that included B Yamagata along with a trivalent. And do you think there's any reason that there would be a difference in the immune response between those?

[2:18:05]
Um, the next question, did you look at cellular immunity? We don't know really what the role of T cells play in influenza, but was there any effort to look at that? And then, um, the final question I have is people would, I think, be very interested in a comparative trial between a high-dose influenza vaccine or cell-based influenza vaccine, such as flu block and some of the standard egg-based vaccines. And, um, can you anticipate any comparative trial that we might, uh, we might see in the future? So, I'll stop there. It's probably an unfair number of questions, but I also have a comment for Dr. Duggan.

[2:19:05]
So, I'll stop at this point. Dr. Kulldorff, thank you.
[Martin Kulldorff]
Uh, thank you. Please, Dr. Fallegati. Thank you very much for your questions.
[Pedro Folagatti]
These are really good ones. So, I'll start with the first one. So, why have we chosen the nine years and above? So, you're absolutely correct in your interpretation. So, the recommendation that we have is for a single-dose vaccine administration from children aged nine years and above. The assumption we have is that by that time, um, children from nine years of age and older, they're expected to have similar immune responses to adults. So, that's why, in this study, we, um, uh, stopped at nine years and above. Um, with regards to your second question, so we did have a subgroup analysis where we looked into, um, the influence of baseline serostatus and also whether the, um, uh, if some participants had received an influenza vaccine in the previous season and the overall conclusions remained the same, uh, regardless of, uh, serostatus or, um, previous vaccination in the, in the preceding year.

[2:20:19]
Um, uh, regarding specifically about the fact that, yes, uh, we did observe bad immune responses in children. They also had, uh, higher baseline, uh, titers. But when you look at the fold increase, so their ability in amounting in immune responses compared to adults, the fold rise is, uh, uh, highly comparable. Um, and then the other question I had was whether we've looked into cellular immunity. No, we have not looked into cellular immunity in this trial.
[Cody Meissner]
And the last question of, about a, uh, a head-to-head comparative trial with, uh, Flublok and, and some of the other vaccines.

[2:21:01]
Yes, thank you. Thank you for that question, Dr. Meisner.
[Pedro Folagatti]
Um, we have got data on hand of comparative, uh, uh, comparison of Flublok versus standard dose vaccine, most notably, uh, cluster randomized study that came out of Kaiser Permanente. Um, and we're happy to share that data and all other data we have, um, with you.
[Cody Meissner]
It has been presented to this group before, the Kaiser data. Okay, thank you. And can you, can you comment on the results or briefly? Yes, there, there was a relative vaccine efficacy in favor of, uh, of Flublok versus standard dose. And that was a serologic study, not, uh, efficacy? No, it was an efficacy study. Okay. Um, thank you. I will have to look for that reference. We're happy to share that with you following this meeting. Oh, thank you. And, uh, in terms of the immune response to a trivalent versus a tetravalent vaccine, they should be similar.

[2:22:09]
Yes. Okay. Um, Dr. Duggan, I, I really appreciate the data that you presented. It was wonderful. I want to make one comment. Um, a lot of times people, what I hear is that people don't want to get the influenza vaccine because it's not as effective as other vaccines that we're accustomed, uh, to living with, such as, uh, the measles vaccine, which offers excellent protection. And, um, I think the point that, that you made that's so important is that even though efficacy may be considerably less from the current generation of influenza vaccines, the fact that probably 10 to 15% of the American population, that is, um, between 30 and 40,000, 30 and 40

[2:23:07]
million Americans, um, develop influenza illness, even if the vaccine has limited efficacy relative to other vaccines, because the number of people who get infected is so large that, um, even a, a relatively small benefit has an enormous impact on the public health of our country. And so you may want to kind of comment on that. And then the, but the question I have for you is, can you tell us, have you collected data on what percent of influenza vaccines this year were administered at home, uh, by individuals over 18 years of age with flu mists? How well has that, has that been accepted? Just thinking about, uh, going forward. Thank you very much.
[Vivian Dugan]

[2:24:01]
Thank you very much, Dr. Meyers. I really appreciate, uh, your, your questions. I think for the, your first comment, just to add that, um, based on our estimates, there would have been approximately 1 million hospitalizations without the vaccine this, this season, 2024, 2025. So really, um, underscores the importance of, of vaccination overall for influenza burden. Um, as far as, uh, the, uh, self-administration for, for flu mists LAIV, that is coming for the 2025, 2026 season. So it is not yet available. Um, but they, it is expected to be available. I'm not sure if there's anyone from, uh, AstraZeneca on the line that might want to provide any details there.
[Martin Kulldorff]
Uh, it doesn't seem so. So, uh, uh, we are running a little bit behind time, but I want to make sure that if there are any members of the, uh, voting members of the committee who has not spoken yet, if you have questions or comments, please talk to me live.

[2:25:10]
So, uh, thank you again.

Discussion on Assessing Vaccine Efficacy and Burden Aversion

Thank you for the presentation and the extensive analysis.
[Retef Levy]
Um, I, the first thing I would like to say is that it would just to anchor the sentiment of, uh, conducting clinical trials to compare the effectiveness, the efficacy of different vaccines. I think it's important to continue to do that. Um, I do have a question, um, that has to do with the, what burden of, uh, what burden of influenza is being averted by, by vaccination and which is also related to how do we assess the vaccine efficacy year to year? Um, I, I, I just want to point out that, um, you know, it's, it's, it's a rather challenging task. Um, so I want to ask the, uh, colleagues on the CDC, um, whether in addition to the existing approaches, do, are we using any negative controls approaches to understand potential, um, um, impact of healthy vaccine effect?

[2:26:10]
Um, and the second thing is that when I looked on your model to assess the aversion, um, or what would be the burden without, uh, without, uh, vaccination, it seems that it's, it's going, it's monotone in the observed number of hospitalizations. Um, and I think if that's the case, I think that there is some potential concern here because, um, if I look on the overall, if I consider the burden on hospitalizations is a function of the overall potential burden and the efficacy of the vaccine. So if the burden, the observed burden is going up, it could be for two reasons, maybe both. One is that the initial burden, the base burden is higher and, or that the vaccine is maybe not as effective on that particular season.

[2:27:00]
And we know that that could vary. So I, I wonder how, I want, it would be good to, um, get your thoughts about how do you think about those, those kind of concerns and, and, and what can we do to get more precise answers? Thank you.
[Vivian Dugan]
Thank you. Vivian Dugan, Influenza Division, CDC. Um, I'm probably going to defer to a lot of my experts, uh, who run these models, um, on the line, but I can say that, um, you know, overall we do look at our models and we do test and stress test them and look at other ways of, ways to improve them, um, overall and new data types to try and again, give us more clarity, more granularity overall. Um, but in thinking about, of course, what goes into overall burden, there's certainly merit that there are many factors that will play a role on the effectiveness of the vaccine, uptake of the vaccine, attitudes towards the vaccine, the timing of the season, the co-circulating viruses, the predominant virus, um, the antigenic relatedness of the vaccine to what's circulating. So there's a lot of, of activity to think about overall. So with that, um, but I'll ask, uh, our modelers on the line to, to chime in, please.
[Karen Reed]

[2:28:06]
Yeah. Hello, Dr. Carrie, Carrie Reed from the Influenza Division again. Um, and thanks for your question. So yes, that is correct. That, uh, there's three components as, as was mentioned into the, the models, uh, to estimate, uh, preventive burden, the burden that's observed during that season, which varies from season to season, uh, vaccine coverage during that season, and then the effectiveness of the vaccine as measured during that season from the vaccine effectiveness studies that are conducted that year. And so it's, it's true that in years where the burden is higher because there's more flu circulating in the population that season, uh, even the same effectiveness of the vaccine, uh, may have a bigger impact in terms of the total number of averted outcomes because there's a greater incidence in the population, a greater risk of, uh, influenza to the general population.
[Retef Levy]
Yes, I, I guess I just want to point out that there is some endogeneity here, right?

[2:29:02]
Like we should recognize that potentially the, the burden that we see is the function of the efficacy of the vaccine. So I think maybe my, my suggestion that maybe, uh, we, we should try and put some effort to think about what else we can do to try and get these, these models more precise, because I, I'm concerned that some of these estimates might be coarse and, and, and, and maybe not precise enough to understand very important issues that we, we want to monitor over time is, is how efficacy, what is the efficacy of these vaccines and how do we get better in, in, in dealing with a very serious illness.
[Vivian Dugan]
Thank you.
[Martin Kulldorff]
Thank you so much. We are going, we are running behind time.

Public Comment on Financial Burden of Influenza

So we're going to have just one more question and that's from Dr. Jason Goldman. Uh, so, and, and please, thank you so much.

[2:30:00]
Thank you, Jason Goldman, American College of Physicians, observation and question.
[Jason Goldman]
First, just want to point out 250,000 pediatric deaths is not a small number, especially if it's your own child dying from a vaccine preventable illness. But number two, as far as the impact of flu, it would be helpful to look at modeling studies on the financial burden of the infection and what is averted when you consider not only the cost of hospitalization, but the impact on the healthcare system, how many patients are seeking care in clinics and urgent care, how that is displacing the amount of available healthcare for those who are sick with other conditions that could have been seen if patients did not have to go to clinics, urgent cares, hospitals for flu, as well as the individual's loss of revenue, the loss of ability to care for those that they may be responsible for and caregivers giving a vaccine to those who are younger, who are

[2:31:04]
taking care of the elderly is also a consideration. So those economic modeling studies and financial impact would also be helpful because vaccinating for the flu not only decreases hospitalization and death, it also saves lives and also has a tremendous benefit to preventing a huge financial burden on the healthcare system to allow more patients to be seen and to be healthier, which is our goal. So I would appreciate that the committee take that into consideration as well.
[Martin Kulldorff]
Thank you. Thank you, Dr. Goldman. And Dr. Duggan, please.
[Vivian Dugan]
Sorry, Dr. Goldman, just to correct and hopefully I did not misspeak, but it's 250, 250 influenza-associated pediatric deaths this season, not larger than 250.
[Martin Kulldorff]
Thank you so much.

Break

It's now 10.15. Before the next presentation, we are going to take a 15-minute break.

[2:32:02]
So we will reconvene at 10.30. And I would like to thank all the presenters and the excellent discussions we've had. Thank you.

[2:49:05]
I hope you had a good 15-minute break.

Resuming Meeting and Presentation on Thimerosal in Vaccines

We are now continuing. And the next presenter is Lynn Redwood. So, please.
[Lynn Redwood]
Thank you, Martin. I just want to state that I'm presenting today as a private citizen, and I am not representing any federal agency. Next slide, please. The recognition that infants and children were being exposed to levels of mercury that exceeded EPA federal safety guidelines from vaccines was due to an act of Congress. The Food and Drug Administration's Modernization Act of 1997 mandated the FDA to compile a list of drugs and foods that contain intentionally introduced mercury compounds and provide an analysis of the types of mercury and the exposure levels.

[2:50:04]
What was most concerning was the identification of several pediatric vaccines that utilize multidose vials, including inactivated flu vaccines, DTAP, Hib, Hepatitis B, and other formulations along with immunoglobulin therapies such as Hepatitis B. Next slide. In July of 1999, a joint statement was issued by the Public Health Service and the American Academy of Pediatrics which called for the immediate reduction and elimination of mercury-based preservative, thimerosal, from infant vaccines based on the findings that infants and children who received these vaccines could be exposed to mercury in excess of federal safety guidelines. And because any potential risk of concern, the Public Health Service and AAP and vaccine manufacturers all agreed that thimerosal-containing vaccines should be removed as soon as possible.

[2:51:00]
Next slide. In October of 2001, the Institute of Medicine's Immunization Safety Review Committee Oops, wait a second. I think I've missed a slide there. Okay. Immunization Review Committee released a report on thimerosal-containing vaccines and neurodevelopmental disorders. The committee supported the prior decisions made by ASAP and the AAP to call for the removal of thimerosal from vaccines that are part of the recommended childhood immunization schedule. But they also noted that some vaccines that are not part of the recommended childhood immunization schedule still contain thimerosal as a preservative and could be given to some children. Those included DT, TT, influenza, pneumococcal vaccines, and other lingering concerns about an unknown quality of thimerosal-containing Hib, hepatitis B, and DTAP vaccines that were still on the shelf.

[2:52:00]
The committee recommended that the use of thimerosal-free DTAP, Hib, and Hep B vaccines, despite the fact that there might be remaining supplies of thimerosal-containing vaccines available, and that full consideration be given by appropriate professional societies and government agencies to removing thimerosal from vaccines administered to infants, children, or pregnant women in the United States. Unfortunately, these recommendations were not acknowledged or implemented. Next slide. The FDA assessed thimerosal use in vaccines in 1997 to 1999, and they were unable to locate any clinical studies formally evaluating the use of thimerosal before its initial marketing in the 1930s. FDA found one study published in 1931 where thimerosal was administered to individuals suffering from meningococcal meningitis. The study was not designed to specifically examine toxicity.

[2:53:01]
There was no clinical assessments, and there was no laboratory studies reported. In the paper, the authors acknowledged that the clinician who was treating the meningitis patients was not convinced of its efficacy, stating beneficial effects of the drug were not definitively proven. Industry scientists noted in 1930 that a wide range of toxicity and injury tests should be done, but there's no evidence that these studies were ever conducted. FDA grandfathered in thimerosal without formal submission of any animal safety data. Next slide. Thimerosal was first introduced as a preservative in vaccines in the 1930s after being developed and patented in 1927 and subsequently marketed by Eli Lilly under the trade name of mirthyolate in 1928. After a deadly incidence of bacterial contamination of vaccines in Australia where 12 children died from staphylococcal-contaminated diphtheria vaccine, the FDA developed regulations requiring that all multidose vaccines contained a preservative to prevent contamination.

[2:54:09]
Thimerosal is used during the manufacturing process and when packaging multidose vials to prevent bacterial and fungal contamination. And by the 1930s, thimerosal became widely used as a preservative in vaccines and other medical products. Next slide. Starting in the late 1920s, scientists began voicing concerns regarding the effectiveness of thimerosal and published several articles arguing thimerosal was ineffective. As a result, the FDA convened a panel of experts to evaluate the use of thimerosal and over the counter products. The panel reported that thimerosal was 35.3 times more toxic for embryonic chick heart tissue than for staphylococcus aureus. They also found evidence that thimerosal was no better than water in protecting mice from potential fatal streptococcal infections.

[2:55:00]
The FDA issued a report of the panel's findings in the Federal Register in 1982 which concluded that thimerosal was not safe for over the counter topical use because of its potential for cell damage and that it was not effective as a topical antimicrobial because of its bacteriostatic action could be reversed. In response, the FDA reported in April of 22, 1998 in the Federal Register final rule making that it concluded the use of thimerosal and over the counter products is not generally recognized as safe or effective. Next slide. Thimerosal has not been shown to prevent all bacterial contamination in vaccines as evidenced by clusters of disease of group A streptococcus infections traced to multidose DPT vials that were contaminated after opening. Thimerosal was present in acceptable levels in unopened vials of the vaccine from the same lot.

[2:56:04]
The authors concluded that preservatives and multidose vials do not prevent short term bacterial contamination and the only feasible and cost effective preventative measure now is careful attention to sterile technique when administering vaccines for multidose vials. Next slide. A more current in vitro investigation into the cytotoxic effects and antimicrobial activity of thimerosal was published in 2023 that mirrors the previous research. The authors reported that thimerosal should be present in culture media at 100 micrograms per milliliter which is the concentration that was necessary to achieve effective antimicrobial activity but all tested cells lost viability at 4.6 micrograms per milliliter. They concluded that overall the study revealed thimerosal was 333 fold more toxic to human and animal cells as compared to bacterial and fungal cells.

[2:57:10]
Our results promote more study of thimerosal toxicity and its antimicrobial effectiveness to obtain more safe concentrations and biopharmaceuticals. Those were the conclusions of the authors in 2023. The research that resulted in thimerosal not being recognized as being generally accepted as safe and effective and over the counter products was published decades ago but today those concerns still exist. Next slide. In 1987 the commission of the European communities initiated a research project on 10 known or suspected spindle poisons. Thimerosal was found to cause significant interference with microtubule polymerization destabilizing the spindle machinery that ensures accurate chromosomal separation during cell division.

[2:58:00]
This mechanistic disruption suggests direct mutagenic potential via structural chromosomal abnormalities which is a known pathway to carcinogenesis and congenital defects. By affecting fundamental cellular structure at the molecular level thimerosal revealed strong mechanistic evidence for mutagenicity and developmental toxicity even before in vitro confirmation. Next slide. California's proposition 65 is a state law that requires California to identify chemicals known to cause cancer, birth defects or other reproductive harm and to ensure public warnings when people might be exposed to them. Thimerosal has been recognized as a prop 65 chemical since 1990. In 2003 a petition was filed on behalf of the Bayer corporation for reconsideration of the determination that mercury and mercury compounds as reproductive toxicants which included thimerosal in the listing.

[2:59:06]
The California EPA responded and this is a quote, the scientific evidence that thimerosal can cause reproductive toxicity is robust. Thimerosal disassociates in the body to ethylmercury. The evidence for its reproductive toxicity includes severe mental retardation or malformations in human offspring who were poisoned when their mothers were exposed to ethylmercury or thimerosal when pregnant. Studies in animals demonstrating developmental toxicity after exposure to either methylmercury and data showing interconversion to other forms of mercury that also clearly cause reproductive toxicity. Next slide. A study published in Pediatrics in 2000 measured blood levels in preterm and term infants after administration of the hepatitis B vaccine containing 12.5 micrograms of ethylmercury.

[3:00:01]
The investigation documented elevated post immunization concentrations relative to pre immunization levels and all neonates studied. Levels of blood mercury after exposure in low birth weight infants were 7.36 plus or minus 4.99 micrograms per liter. One infant was found to have developed a mercury level of 23.6 micrograms per liter thus meeting CDC's criteria as a case of chemical poisoning for mercury which the level for that is 10 micrograms per liter. The study subjects had measurable blood concentrations prior to immunizations indicating that risk assessment should also include background mercury levels from other sources. Next slide. Experts contend that there are windows of vulnerability which occur during neurological development and that specific types of developmental outcomes may have separate windows of vulnerability. These critical periods of development have not been established and they may be relatively short in duration.

[3:01:03]
The fact that thimerosal from vaccines has been documented to raise blood mercury levels over known thresholds where developmental effects have been documented to occur during the first few months of life means that particular windows of vulnerability may have been breached. Even minor neurological impairment can have profound societal effects when it's amortized across the entire population and lifespan. Next slide. A 2005 study funded by the National Institutes of Health compared brain mercury levels in infant macaques exposed to injected ethyl mercury thimerosal that was modeled after vaccine exposures and equal amounts of ingested methylmercury. In this study, ethylmercury more rapidly converted to inorganic mercury in the brains of the primates which resulted in increasing levels of inorganic mercury. In fact, the primates exposed to the ethylmercury retrained twice as much inorganic mercury in their brains compared to the primates exposed to methylmercury.

[3:02:05]
The relative concentration of monkeys with detectable levels of inorganic mercury were twice the amount as the methylmercury group, methylmercury treated monkeys, which inorganic levels and the ones where inorganic levels were detectable. Inorganic mercury is below detectable levels in eight out of 17 of the methylmercury treated monkeys. Why this is important is that once inorganic mercury compounds reach the brain tissue, they rapidly dealkylate into HG2+, excuse me, which is a toxic form of inorganic mercury that gets trapped in the neurons as it cannot penetrate back out through the blood-brain barrier. Next slide. A recent review outlined evidence from human case studies, animal models, and modeling assessments that estimated an inorganic mercury half-life in the human brain of at least five to 27 years.

[3:03:03]
The impact of mercury exposure to the developing brain interferes with neuronal proliferation, migration, neuronal differentiation, synaptogenesis, and tightly regulated apoptosis and other processes vital to the formation and functioning of the nervous system, which can result in lifelong impacts. Exposure during the first trimester of pregnancy may result in deficits or defects very different from those developed by someone who is exposed during the third trimester of pregnancy. And the authors also summed up that there may be, there may not be a safe level of mercury exposure, especially for an unborn child. Next slide. Thimerosal is 49.6 mercury by weight, and the standard concentration in flu vaccines is 0.01%, which equals 50 micrograms per 0.5 milliliter dose.

[3:04:02]
This equates to 100 micrograms per milliliter of thimerosal and 50 of mercury in the vaccine solution. EPA's toxicity characteristic leaching procedure is used to determine whether a substance is considered a hazardous waste based on its potential to leach toxic chemicals into groundwater. According to EPA's TCLP, the mercury threshold is 0.2 milligrams per liter or 200 parts per billion or 200 micrograms per liter. Flu vaccine concentration is approximately 50,000 micrograms per liter, which is 250 times greater than the TCLP limit. Therefore, thimerosal containing vaccines exceed the TCLP threshold by an orders of magnitude and are classified as D009 hazardous waste.

[3:05:03]
This slide is an image of information that's available online with regard to the appropriate disposal guidelines for the 2025 flu season. And I want to highlight the very last paragraph, which states all full or partially used multidose vials of seasonal flu vaccine should be disposed of as a federally hazardous waste. But I've not seen this information being distributed to clinicians who are administering flu vaccines or something that the general public is aware of. Next slide. I just wanted to point out the most susceptible populations with regard to exposure to mercury. Obviously, pregnant women and the developing fetus are the most vulnerable to mercury exposures, and this is followed by young children.

[3:06:00]
There was a landmark study published in 2003 by Stern that actually found that infants when born, when they tested cord blood to the maternal blood, had a much higher level, 1.7 times higher than the mother's blood at birth. The rapid neurodevelopment that takes place prenatally in the first years of life, along with immature detox pathways and the possibility for genetic susceptibility is why the Institute of Medicine in 2001 recommended that these sensitive populations not be exposed to mercury. And also, you'll see there that older adults can also be at risk, and there's been several studies that have come out over the last few years that have found elevated levels of mercury associated with cardiovascular disease. Next slide. In summary, mercury is the third most toxic element on Earth, only behind polonium and plutonium.

[3:07:01]
It has no physiological role in the human body. Thimerosal was grandfathered for use without adequate safety testing by the FDA, and it's not generally recognized as being safe or effective by the FDA over the counter division since 1998. There's also evidence that thimerosal is not an effective preservative at vaccine levels, and that thimerosal can cross the placenta and blood-brain barriers and converts to inorganic mercury in the brain at higher levels than methylmercury. Studies have identified infants with blood levels after exposure to thimerosal-containing vaccines that breach CDC guidelines for a case of mercury chemical poisoning. Hold on. Next slide, please. Thimerosal is recognized as a developmental and reproductive toxicant and is listed as a chemical on the California Proposition 65 list since 1990.

[3:08:02]
Unused doses of thimerosal-preserved flu shots must be disposed of as a hazardous waste. And tremendous progress has been made in removing thimerosal. But from data that I recently received, more than 60,000 pregnant women received thimerosal-containing flu vaccines through Medicaid in the 2019-2020 flu season. We currently have enough thimerosal-free vaccines to recommend that all pregnant women, infants, and children receive only thimerosal-free vaccines. After a critical appraisal of this issue almost 25 years ago, the prestigious Institute of Medicine made this same recommendation. Removing a known neurotoxin from being injected into our most vulnerable population is a good place to start with making America healthy again. Thank you. Also, I believe one of the FDA people are here that could possibly comment on what the availability is for thimerosal-free flu vaccines as well.

[3:09:08]
Thank you very much, and I'll be glad to answer any questions.

Discussion on Thimerosal in Vaccines

[Martin Kulldorff]
Thank you for that. I think I'm going to make the first comment. We know that mercury is a toxin. We cannot completely avoid exposure to mercury, but it's a cumulative issue. So we already have some exposure to mercury from other sources. So even if the amount available in the vaccine, maybe that amount is safe, but that's not the amount we're exposed to. We're exposed to mercury from other sources, so it's cumulative. And there is a need. And if we care about public health, we should try to minimize exposure to mercury. I know that FDA do not allow mercury, for example, in skin products.

[3:10:02]
If that's the only exposure you had, that would probably be safe. But we want to minimize the cumulative exposure. So the first argument for not having mercury in the vaccines is that it's a cumulative exposure. The second thing for seasonal influenza vaccines, there are alternatives. And in fact, most of the influenza vaccines given today do not contain mercury or thimerosal. They are in single dose. So it's very feasible, I think, very feasible to not use thimerosal containing vaccines for seasonal influenza. So we don't really need it. And the third thing is that I'm not an expert on marketing.

[3:11:00]
But if we put mercury in a product, people are not going to want to buy those products. If we put mercury in cereal, that's not a good idea, because a lot of people won't buy the cereal if we have mercury in it. So if we want to have confidence in vaccine and we want to promote people taking vaccines, we should remove this mercury-containing preservatives from the seasonal influenza. So those are my view on this matter. And I will now open up to other members of the committee to do comments or questions. Dr. Malone, please.
[Robert Malone]
Dr. Robert Malone, Director, National Institute for Disease Control and Prevention. One minor addition point is that we're speaking about seasonal influenza, which is recommended for redosing on an annual basis. So that would be for those unfortunate few receiving doses from a multidose vial, which I don't know the profile of who those people might be, but one could speculate there might be a bias towards underserved populations or populations that don't have access to the same level of financial resources because the cost of single dose is a little bit higher.

[3:12:26]
That means that we do have a risk of repeated exposure to this. So it's not just a one administration, but a potential chronic exposure through lifetime on an annual basis over. Thank you. Dr. Leroy?
[Retef Levy]
First, I would like to concur with the last two comments. I also think that we need to emphasize that there is somewhat an implicit trade-off that we either use mercury or we are taking a risk of contamination of fungal and bacterial contamination.

[3:13:03]
I think we should reject that trade-off. I think we should have integrity of the supply chain and handling of vaccines and drugs that we provide to patients. I think that there are technologies that should allow us to identify in real time a potential contamination, and we need to think seriously about how we either prevent them better or be able to detect them in real time and prevent them from getting to patients. So I think that's another aspect that is maybe not directly related to the issue, but I think I want to kind of highlight it.
[Martin Kulldorff]
Yeah, I think the single dose that are the ones that are mostly used today does not contain thimerosal, and there's no problem with contamination at all because it's a single dose. Any other questions or comments from the members of the committee?

[3:14:02]
Pardon? We have Jay? Okay, Dr. Meissner, please.
[Cody Meissner]
Thank you, Dr. Kulldorff. I'm not quite sure how to respond to this presentation. This is an old issue that has been addressed in the past, and there are many aspects, I think, that we could discuss, but we don't have time to go into it here. I guess one of the most important to remember is that thimerosal is metabolized into ethyl mercury and thiosalicylate. It's not metabolized into methylmercury, which is in fish and shellfish.

[3:15:05]
Ethylmercury is excreted much more quickly from the body. It is not associated with the high neurotoxicity that methylmercury is. And as many experts, vaccine experts have said, including Paul Offit, you know, all vaccines that are routinely recommended for young children in the United States are available in formulations that do not contain thimerosal as a preservative. This is also true for adolescents and adults, including pregnant women. So, of all the issues that I think ACIP needs to focus on, this is not a big issue.

[3:16:00]
I will also hasten to add that thimerosal is included in most vaccines that are administered around the globe, and that is because single-dose vials are more expensive. And many countries cannot afford a single-dose vial. Now, I realize ACIP is focused on the United States, but the recommendations that the ACIP makes are followed among many countries around the world. And removing thimerosal from all vaccines that are used in other countries, for example, is going to reduce access to these vaccines. It will increase cost. And I think it's important to note that no study has ever indicated any harm from thimerosal.

[3:17:09]
It's been used in vaccines, as was noted by Ms. Redwood, since before World War II. The decision by the FDA to remove thimerosal as much as possible is a very reasonable recommendation. But this recommendation was made not because there was any evidence of harm from thimerosal. It was made in an effort, as you said, Dr. Kulldorff, to reduce the total exposure to mercury in our environment. That's a reasonable objective. But you also have to consider what are the consequences of these sorts of recommendations. So, I'm not sure if we're going to have a vote here or wording, but I don't think this is an issue.

[3:18:10]
Over.
[Martin Kulldorff]
Thank you. Yes, sorry. We'll have a response from Lynn Redwood first.
[Lynn Redwood]
Yes, just real quickly. I want to point out that in a lot of the studies that have been done, like the HICARO study, they looked at blood levels. And they found that the thimerosal, when infants were exposed to thimerosal, the blood levels were lower and it seemed to leave the body more quickly. But what we have learned is that thimerosal has a higher binding affinity for tissue. And that just because it left the blood, it didn't mean that it exited the body. And in fact, what we're finding is that blood is not a good predictor in terms of toxicity.

[3:19:06]
Because blood is not the organ of toxicity. The brain is the organ of toxicity. And even if you have lower blood levels from ethyl mercury, ethyl mercury has a higher blood-brain ratio than methyl mercury. So, even at lower levels, more will get into the brain. And when we looked at the conversion and we looked at inorganic mercury, which is what is really the toxic element that gets trapped in the brain, the inorganic mercury in the ethyl mercury primates was like 70%, and it was only 10% in the methyl mercury primates. So, I'm just going to have to say that I don't know that scientifically the argument that methyl mercury is safer than ethyl mercury based on the Burbacher study would not prove that out. Also, in terms of third-world countries, I want to remind the committee that there are other approved preservatives that can be used in place of thimerosal, for example, tufenoxyethanol.

[3:20:06]
So, and I think there's other things that we can do as well. We have made such tremendous advances that we should not be relying on a product that is so neurotoxic when there's other safer preservatives available as well.
[Cody Meissner]
I would just like to respond, if I may. Please go. The ACIP makes recommendations based on scientific evidence as much as possible. And there is no scientific evidence that thimerosal has caused a problem. And you are correct. There are several other preservatives that could be used.

[3:21:01]
Benzothonium chloride, tufenoxyethanol are alternatives, but they have not been studied to the same extent. Tufenoxyethanol is, in fact, I believe that's included in the polio vaccine. But to make the industry jump through hoops for something for which there is no evidence of harm, I think is an issue that needs further discussion. Thank you.
[Martin Kulldorff]
Thank you, Dr. Petzworth.
[Vicky Pebsworth]
I would just like to say that on the basis of the precautionary principle and the fact that women early in pregnancy could continue to get flu vaccine that contains thimerosal, if there's a way to phase this out to eliminate its use, because it is a known neurotoxin, we should make every effort to do that.
[Martin Kulldorff]

[3:22:16]
Thank you. Dr. Levi.
[Retef Levy]
Yeah, I may want to share a different perspective about understanding the risk. I think that the notion there is no evidence that it causes harm is a somewhat tricky notion in this setting, because we have to define what the harm, what the potential harm is. If the potential harm is some cumulative exposure, then I think we need to do whatever we can do to control the controllable sources of exposure, because there are some uncontrollable ones that we may not be able to control. So, I just, and I think that that's true for other aspects. I know we kind of committed to also look on the cumulative impacts of vaccination.

[3:23:01]
These are the same kind of issues that if you start looking one by one on each specific exposure, you might conclude, okay, nothing wrong with that, but if you try enough time and in a cumulative way, you might actually, you might have some harm. And in this case, it's clear you have harm. So, it's actually, that's not debatable based on my understanding of the evidence. So, I just think that we need to adopt a more kind of holistic, long-term kind of perspective about what the risks are.
[Martin Kulldorff]
I think that's an extremely important point. Let's say a child is exposed to mercury from 10 different sources. Each of those 10 sources might be small enough that that source in itself is not dangerous. But if you then put all 10 together, then it might be dangerous. So, it's a cumulative exposure. So, that means that if you did a study on every one of these 10, you would not find anything.

[3:24:00]
But we know that mercury is a toxin. So, the key thing is to minimize the total exposure, the cumulative exposure. And we do that by removing the exposure in any way we can. And there are some exposures we can't remove. But whatever we can remove will help reduce the total amount of exposure to mercury. And we do know that mercury is a toxin. I don't think anybody is claiming that it's not. Dr. Hibble.
[Joseph Hebelin]
Thank you. Should this committee vote affirmatively to this question, I think that we should note that we, that the precautionary principle is not a mandate for us to make decisions. That also with the question of cumulative doses, there is still no demonstrable evidence of harm that we can evaluate.

[3:25:07]
And that is certainly a departure from the criteria used by this committee. And alternatively, we need to be aware, as noted, that the fear of mercury is substantial. And the fear of mercury in causing people to not get vaccines is a risk in itself. Whether the actual molecule is at risk or not, we have to respect the fear of mercury as a potential toxin to avoid people getting vaccines. Thank you. Thank you.
[Martin Kulldorff]
And those psychological aspects is actually a very important part of public health science. So if you want to do things evidence-based, that is part of the equations. Dr. Malone.
[Robert Malone]
I request comment from our representative from the FDA, particularly concerning the magnitude of potential impact both in influenza vaccines, ergo, how many, what fraction of doses are we actually talking about in the United States?

FDA Comment on Thimerosal Availability and Use

[3:26:19]
And whether there's a, you know, what is the current status of thimerosal in any other vaccine products other than multidose influenza vaccine products? And any other aspects of this that the FDA can help inform the committee of? Over.
[Tracy Beth Hogue]
Sure. Yeah, this is Tracy Beth Hogue from the FDA. And so the data that I've been provided with by CBER, and I thank them for their help. It looks like less than 5%, between 4% and 5% in the 2024-2025 season of influenza doses were multidose thimerosal-containing vaccines.

[3:27:02]
And so the remainder were single-dose preparations. And moving forward, I want to confirm what Lynn stated, that next year, that for the next season it does not look like we would be limited in terms of availability if we were to switch to only using the single-dose preparations. And again, I've had this confirmed by my CBER colleagues. And to my understanding that this is the only current vaccination on the childhood schedule that children could potentially receive are pregnant women containing thimerosal.
[Martin Kulldorff]
Thank you for that.

Public Comments on Thimerosal and Vaccine Safety

We also have some comments. And we're going to go to Stacey Buchanan first.
[Stacey Buchanan]
Good morning.

[3:28:00]
Can everyone hear me?
[Molly Howell]
Hello?
[Stacey Buchanan]
We can hear you. Okay. I was just making sure. So I'm Dr. Stacey Buchanan. I represent the National Association of Pediatric Nurse Practitioners. And I was just wanting to comment and make sure that it's very clear that none of the pediatric vaccines on the schedule, the childhood-adolescent schedule, contain thimerosal. And what I was just doing a brief cursory dive to see, and there's only about three products that contain thimerosal was listed on the FDA website for multidose influenza products. So I really wanted to key into this because we're taking time to discuss it. And the potential exposures are very, very limited. Back in 2001 is when the thimerosal was removed from a lot of the products that reach children.

[3:29:02]
So I just wanted to emphasize that. And thank you, Dr. Meisner, for eloquently speaking. Thank you for your time.
[Martin Kulldorff]
Thank you so much.
[Joseph Naima]
And Dr. Phyllis. Thank you, Dr. Kulldorff. Just two quick, one question and a request. Thank you, Ms. Redwood, for the presentation. I wondered if you could share the source of the 60,000 Medicaid patients, just for our information. And then secondly, there was a document on the website, or initially, that was a CDC document on the thimerosal issue. I wondered if that could be reposted as well to accompany Ms. Redwood's presentation. Thank you.
[Robert Malone]

[3:30:09]
This is Dr. Malone. My understanding is that article was not authorized by the Office of the Secretary and has been removed consequent. I'm sure that the Office of the Secretary will make note of your comment and direct the CDC as necessary. Over.
[Martin Kulldorff]
And all of us members on the committee has received that. So we have all read it. So in the committee, we all know about that thing. So Matthew Song, please. Yeah, thank you.
[Matt Zahn]
Good morning. Can you hear me?
[Martin Kulldorff]
Yes. Yes.
[Matt Zahn]
Thank you for the chance to speak. I'm Matt Zahn, liaison from NACCHO, National Association of County and City Health Officials.

[3:31:01]
I just want to make a couple of comments. And I very much appreciate Dr. Meisner's comments. You know, he mentioned it, but I really wanted to amplify the point that Dr. Meisner mentioned there hasn't been evidence of harm done by thimerosal-containing vaccines. But it's really worth emphasizing that that is based on a 25-year robust history of studies that examined the real-life outcomes for children who have received thimerosal-containing vaccines, either in the prenatal or the pediatric period. And children would theoretically be at the highest risk because they are neurodeveloping and because they are receiving more of these vaccines. But studies in multiple different countries where thimerosal continues to be used, as Dr. Meisner said, that were used around the world, the United Kingdom, Sweden, Denmark, they have done cohort studies, meaning look at all the children born over a one-year or multi-year period of time in those countries and compared the neurologic outcomes of those kids

[3:32:01]
who have received thimerosal to those who are not. And again, neurologic outcomes are thought to be the one, you know, primary risk that we're talking about. These were large, well-conducted studies. The totality of evidence from those studies strongly indicates there isn't an association between thimerosal and adverse medical outcomes in children. And, you know, based on that, thimerosal has continued to be offered. Now, again, it's not in the pediatric vaccine series, but I still think this data is pretty powerful in terms of demonstrating the safety of these vaccines. And I think someone had mentioned that, you know, the psychological concerns of thimerosal being the vaccines. I would note that, you know, as Dr. Meisner mentioned, I don't see this as a very large public health issue. And what are the psychological issues associated with broadcasting widely the notion that this question has not been answered or is a significant issue that CDC needs to dedicate public health resources to?

[3:33:02]
I feel like it's a question that's been answered. And I feel like, as a PEDS-ID physician, as a public health practitioner, I'm very confident that thimerosal-containing vaccines are safe.
[Martin Kulldorff]
Thank you. Thank you. Joseph Naima?
[Joseph Naima]
Hi. Thank you for the opportunity to speak. This is Dr. Naima Joseph. I'm a maternal fetal medicine physician, and I'm here representing the American College of Obstetricians and Gynecologists. I wanted to emphasize a couple of points. First, that I appreciate this committee's attempt to portray transparently some concerns from the public, including the risk of thimerosal. But I wanted to emphasize the previous speaker's comments, as well as comments made by Dr. Meisner regarding the overwhelming evidence over multiple decades of research that support one, that the main ingredient has been removed from most products, but two, the safety. And I wanted to address particularly the concerns about exposure, prenatal exposure, and that during pregnancy. And as a physician, and again, as part of the expert committee for ACOG, when we make recommendations to our patients and to our society members, one, we are comfortable with the overwhelming data that show that prenatal exposure has not been linked to any ASDs or autism spectrum disorders.

[3:34:19]
That data is concrete. That had been available on the CDC website, which has not been taken down. And second, when we look at the harms associated with influenza during pregnancy, as was demonstrated to this group yesterday, when we looked at infant hospitalization, we saw that the overwhelming majority of hospitalizations occurred in infants who were not eligible for vaccination, proving again that maternal immunization does provide infant benefit against the risk of hospitalization, which we know is associated with extreme psychological risk, maternal-infant bonding, developmental delays, and iatrogenic infection. And third, we know that these do confer pregnancy-related risk in terms of prevention against preterm birth, prematurity, again, associated with developmental delays, psychological concerns for the infant, but also maternal risk.

[3:35:11]
Again, I wanted to point out that this vaccination during pregnancy provides a maternal-infant benefit, two for the price of one, protects against maternal severe disease and secondarily obstetric risk, and then further provides infant protection that is durable, at least for the first two to six months of life. Over. Thank you.
[Martin Kulldorff]
DR. Thank you. Jason Goldman. DR. JASON GOLDMAN.
[Jason Goldman]
Thank you, Jason Goldman, American College of Physicians. You know, once again, Dr. Meisner spoke very eloquently about some of the concerns. You know, this committee has always prided itself on openness, transparency, and review of data and evidence. So, I am wondering if we will have an actual scientific presentation with peer-reviewed literature, strong evidence to actually discuss this issue, as many statements have been made here today without support of science or evidence but merely opinion.

[3:36:07]
So, in fairness, will we be seeing, if necessary, even though the established data for decades really speaks to the safety and efficacy of thimerosal, if necessary, will there be an actual CDC presentation done by staff, scientists, physicians, and those who are subject-matter experts with accurate peer-reviewed scientific data for the ability for the committee to review, or will we have layperson presentations only? Thank you.
[Martin Kulldorff]
DR. Thank you. Molly Howell.
[Molly Howell]
MOLLY HOWELL. Hi. Thank you to the committee. I represent the Association of Immunization Managers, and one of our roles is to prepare and respond to pandemics, and I am wondering how this discussion will impact our pandemic preparedness.

[3:37:01]
My understanding is that multidose vials and potentially thimerosal would be used should there be a future influenza pandemic, and so I don't know if federal partners can speak to how this would impact, if we could no longer use thimerosal-containing vaccines, our pandemic preparedness. My other question is, if there is a concern about thimerosal in vaccines, why is the FDA then not restricting the use of thimerosal in vaccines? Thanks.
[Martin Kulldorff]
DR. DR. Yes, Kelly Goode, thank you for the opportunity, representing the American Pharmacists Association.
[Kelly Goode]

[3:38:04]
I would also like to again ask the question posed by Dr. Goldman about the ACIP process and transparency and seeing the evidence to recommendations, which includes the balance of benefits and harms, the values and preferences of affected populations, the resource implications, the equity considerations, and the feasibility of this question and vote before ACIP. Thank you.
[Martin Kulldorff]
DR. We have a committee here in Redwood who is very knowledgeable about vaccines. This committee will always be open and receive comments from a variety of people. That's part of us being transparent. We had earlier comments today on other topics from the pharmaceutical companies, so we will, that's a principle that we have, and I think it's inappropriate to dismiss a presentation

[3:39:00]
just because the person does not have a Ph.D. or an M.D. There are a lot of knowledgeable people who we would like to hear from, and we want to hear from a variety of viewpoints, and I think today's discussion is a very good example that we have received input from a variety of people on this topic, and we will continue to do that as this committee moves forward at future meetings. There will be, there will eventually be a vote on this topic, but that will be at the end after public comments. We do have a few minutes left before public comments at 11.30, so I would like to move forward now with a five-minute presentation of chikungunya vaccines. That is, it was supposed to have longer, but we will hear more about that at our next meeting, so at this time, just a short, a short presentation about chikungunya vaccine by Dr. Lyle Peterson, please.

Brief Presentation on Chikungunya Vaccine

[Speaker 9]

[3:40:08]
Yeah, thank you very much, and I'm Dr. Lyle Peterson, and I'm the director of the Division of Vector-Borne Diseases here at CDC, and today, I will update you on work group progress on assessing the evidence to recommendations for use of chikungunya virus vaccines among persons in the U.S. territories at risk for chikungunya virus transmission. I will also provide an update on reporting of adverse events following administration of the live attenuated chikungunya virus vaccine. And as was mentioned, given the limitations in time right now, my presentation has been shortened, and the full background information from the slides from the full presentation are in the meeting materials online.

[3:41:01]
Next slide. So, as some background for today's session, there are two licensed chikungunya virus vaccines. A live attenuated vaccine was licensed in November 2023 for use in persons aged 18 years and older, and a virus-like particle vaccine was licensed in February 2025 for use in persons aged 12 years and older. The chikungunya vaccines work group was formed in May 2022, and recommendations have already been approved for use of both vaccines in travelers and laboratory workers. Most recently, the work group has been discussing the use of the chikungunya virus vaccines in residents of U.S. territories and states at risk for transmission. The two components of the evidence to recommendations domain the work group were able to finish discussing before this meeting were the public health problem and the values domains.

[3:42:06]
And given the shortened time frame of the presentation, I will summarize the conclusions of the work group with the full background provided in the complete slide deck online. Next slide. So, for the public health problem domain, the work group concluded that acute illness can be severe, particularly in vulnerable groups, including infants and the elderly, with comorbidities, and that arthralgia can persist for months to years. Also, as a future outbreak is likely to evolve rapidly and might affect a substantial proportion of the population, outbreaks can overwhelm health services, and no highly effective control measures exist apart from vaccination. So, given this, the working group concluded that chikungunya virus can have substantial impact in the U.S. territories, primarily related to large and substantial outbreaks.

[3:43:08]
Next slide. So, the working group also looked at data from surveys conducted in Puerto Rico and the USVI as background for the values and preferences domain for the U.S. territories. The key finding was that most participants were interested in the hypothetical chikungunya vaccine, although interest was higher in Puerto Rico than in USVI, possibly due to survey timing relative to outbreaks, as well as differences in general vaccine uptake in the two territories. For respondents potentially not interested in vaccine, a key concern in both locations was needing a better understanding of vaccine safety. So, for the question, does the target population feel that the desirable effects of vaccination are large relative to the undesirable effects, the work group felt that the response was probably yes, although the working group indicated that there is important uncertainty or variability in how much people value the main outcomes.

[3:44:18]
Next slide. So, finally, I would like to provide a brief update on safety of live attenuated chikungunya vaccine in older persons. Next slide. So, at the April 2025 ACIP meeting, the work group reported on six serious adverse events in U.S. persons age 65 years and older that had occurred during 2024 and were reported through the U.S. vaccine adverse events reporting system. Following discussions at that meeting, CDC determined that age 65 years and older was a precaution to the live attenuated chikungunya virus vaccine.

[3:45:07]
In the three weeks following the ACIP meeting, an additional 11 serious adverse events were reported internationally in persons age 62 to 89 years, most of whom had underlying medical conditions. The reports were mainly from Reunion, an overseas department of France, where a vaccination campaign was being implemented in response to a large outbreak. The European Medicines Agency recommended a temporary pause in the use of the vaccine in persons age 65 years and older, and the FDA and CDC subsequently recommended a temporary pause in vaccine use in persons age 60 years and older to allow investigations of these reports. We are currently awaiting the outcome of the FDA investigation.

[3:46:00]
So, that concludes my report for this morning or this afternoon, depending where you are. But thanks to ACIP, Chikungunya Vaccines Working Group, and to CDC participants in gathering the data of the working group. So, thank you.
[Martin Kulldorff]
Thank you, Dr. Peterson. We're looking forward to receive more information about the Chikungunya vaccines at our next ACIP meeting. My apologies.

Response to Comments on Thimerosal and IOM Report

I think there was a request. Leonore, we wanted to respond to some of the comments that we heard. So, please go ahead.
[Lynn Redwood]
Thank you. Just real quickly.
[Martin Kulldorff]
I just wanted to point out that our next ACIP meeting. My apologies. I don't know what happened.
[Lynn Redwood]
I just wanted to point out real quickly. I know that there was a report that circulated. I believe it focused primarily on the 2004 IOM investigation regarding thimerosal-containing vaccines and autism.

[3:47:08]
And if you actually read that report, there are several important things in there. One is that the committee mentioned repeatedly that these large epidemiological studies would not be able to detect a subportion of the population that might be more genetically vulnerable, which is what one of the hypotheses is. The committee also dismissed findings of immune activation and inflammation in the brains of animal models that had been exposed to thimerosal-containing vaccines because they had changed what would be the criteria from their 2001 report, which was biological mechanism, which was biological plausibility, to 2004 to biological mechanisms. And at that time, we didn't really know what the biological mechanisms were.

[3:48:00]
And so, one of the things that they recommended is that there's no evidence that there's any neuroinflammation or immune activation in the brains of children with autism. One year after that, in 2005, there was a landmark study published by Carlos Pardo that documented exactly that. This was autopsy brain tissue in children and adults that found a chronic, ongoing neuroinflammatory process in the brains. And today, those findings have replicated over and over again, and it's one of the hallmarks that we see in autism. I also wanted to say that there was a study that was published by the CDC here by, let's see, it was Dr. Thompson, early thimerosal exposure and neuropsychological outcomes at seven to 10 years. This was published. I'm just looking it up right now. I'm sorry. I could have brought this information as well. But they found that one of the associations was with tics, and tics can be very debilitating.

[3:49:01]
So, there have been studies that have found evidence of harm. So, I just wanted to make those two comments. There was another one, and I can't remember what it was right now specifically, but those were just the two main comments I wanted to apply. There is evidence. There are studies. I can provide a list of those if the committee would like.
[Martin Kulldorff]
Thank you very much. We will go to the votes now, or the public comments.

Reading of Draft Votes on Influenza Vaccine and Thimerosal

But before that, I will just read what the draft votes are. And there are four. Yeah, so we are not voting now, so there's no motions pending. I'm just reading the draft votes, because we have to do that before the public comments. So, the first one is recommendations for influenza vaccination for the 2025-26 season.

[3:50:03]
ACIP reaffirms recommendation for routine annual influenza vaccination for all persons ages greater than six months who do not have contraindication. The second draft vote, ACIP recommends children 18 years and younger receive seasonal influenza vaccine only in single-dose formulation that are free from thimerosal as a preservative. Draft vote number three, ACIP recommends pregnant women receive seasonal influenza vaccine only in single-dose formulation that are free of thimerosal as a preservative. And draft vote number four, ACIP recommends that all adults receive seasonal influenza vaccines only in single-dose formulation that are free of thimerosal as a preservative. So, having stated that, we can now move to public comments. And so there is a, yes, the correction from CDC, Dr. Thompson.

Public Comments

[3:51:19]
The Medicaid number is greater than 30,000 pregnant mothers per year in 2019 and 20. Not a single flu season. Okay. We are now going to public comments and do we have the list? So we have 13 individuals. The first is Elias Cass, please.
[Speaker 24]
Good morning. As a naturopathic physician specializing in pediatrics, I encounter vaccine hesitancy regularly.

[3:52:02]
Parents might say, I'm worried about mercury in vaccines. I empathize. I listen. But uncritical affirmation is not my job. Instead, I explain the difference between methylmercury and ethylmercury, how they are metabolized differently and how removing thimerosal from vaccines didn't make them safer, just more expensive. Relitigation of questions already thoroughly answered, like the safety of thimerosal, is not advancing radical transparency. It is an insidious attempt to suggest that something was missed or hidden previously. When presenters on the harms of thimerosal refer to fake citations suggestive of generative AI use, it's clear that they are starting from a conclusion and then looking for or inventing evidence to support it. That is policy-based evidence making. It's backwards. We heard hours of data yesterday about the risks of COVID in pregnancy and infancy and the effectiveness of the vaccines, all of which support the prior ACIP recommendation. Was there new or different data driving the HHS directive to obviate that recommendation? If there was, why was it not presented in a public meeting so everyone could read it?

[3:53:03]
Demonstrating radical transparency is not making changes without reason or evidence just to imply the previous institutions did not do their job. Doing so creates unjustified mistrust. We cannot pretend that receiving money from pharmaceutical companies is the only conflict of interest. Some people sell supplements that will supposedly protect children from supposed vaccine injury. Some people receive payments to testify against vaccine manufacturers. Some people create a brand or social media empire around being contrarians. Some people receive lucrative salaries from anti-vaccine organizations. These are all conflicts of interest when it comes to making evidence-based vaccine recommendation for millions of people.
[Martin Kulldorff]
We lost you there, so...
[Speaker 24]
Can you hear me now? Yes, please continue. We must be clear that not vaccinating and the prevarications that lead parents to hesitate means taking on the risk of disease.

[3:54:01]
When we focus on myocarditis risk from COVID vaccines without the crucial context of the cardiac risks of COVID disease, we reinforce that idea. When we belabor the fever from MMR vaccine but not the fever and immune system damage pneumonia and brain damage from measles, we are not protecting the people we set out to help. It's tempting to think that your health is your reward for a series of good choices. But policy is what determines what choices you have, the air you breathe, the water you drink, the vaccines your insurance covers, the diseases present in your community are kept out by community immunity. These are not individual decisions, no matter what wellness influencers tell you. This committee is determining policy that will shape the landscape of our health.
[Martin Kulldorff]
We lost you again, so that is very unfortunate.

[3:55:01]
I think we'll move on to, but thank you very much. I think we heard most of the comments. We move on to Emmett Patterson, please.
[Speaker 27]
Good morning. I come to you today with deep concern for the health of our communities, especially as we face a rising tide of vaccine-preventable illnesses. These illnesses have the power to maim, kill, and destroy American lives. And they're diseases and illnesses we have the tools to stop. I'm a public health professional, and I have focused my entire adult career on public health communications. I have worked from the local to the international level, specifically focused on outbreaks that impact LGBTQ people disproportionately, including HIV, other STIs, and even vaccine-preventable illnesses like Mpox virus and COVID. LGBTQ Americans are already facing an alarming burden of vaccine-preventable illnesses, specifically long COVID. Studies show higher rates of infection, more severe outcomes, and development of disabilities. We cannot afford to strip away the single most effective protection we have, updated COVID vaccines available for all.

[3:56:04]
And let's be clear, the science proves that COVID vaccination dramatically reduces the risk of severe illness, disability, and death, even for people without any disabilities or health conditions. Delaying or limiting access doesn't just cause confusion and sows mistrust in communities like mine. It also costs our lives. Decisions about vaccines must be guided by science and not politics. This means restoring transparency, reengaging expert advisors, and committing to equitable access. Marginalized people in 2025 should not die of diseases we know very well how to prevent, and none of us should have to fight for the protection we know works. I urge this body to reinstate universal COVID vaccine recommendations from children to elders, ensure access for everyone, and make sure the public and public health includes all of us. Thank you for your time.
[Martin Kulldorff]
Thank you so much. Millicent Gorham, please.
[Speaker 18]
My name is Millicent Gorham, and I serve as the CEO of the Alliance for Women's Health and Prevention, a non-profit, non-partisan organization focused on advancing policies that support preventive health.

[3:57:12]
I take seriously my role as a spokesperson for the broader public health and vaccine community when I say this. We have profound concerns about the continuity and credibility of our nation's vaccine infrastructure and the destructive impact that recent actions will have on the prevention of vaccine-preventable diseases. To put it bluntly, lives are at risk, and decades of public health and trust are being actively and carelessly undermined. This is an unprecedented moment. In my more than four decades in health care, I have never seen our country-leading medical societies voice collective concerns in the way that they have over recent events, including in response to the blatant dismissal of evidence that demonstrates COVID-19 vaccination is safe during pregnancy, and to the sudden, irresponsible firing of ACIP's previous members.

[3:58:16]
Our nation's foremost medical experts who have dedicated their careers to science and safety are raising the alarms. We must not ignore them. AWHP's concerns range from the dismantling of processes that have protected the health of generations to the omission of planned discussions at this very meeting and status of evidence-based vaccine recommendations that await approval to why resources are being used to re-debate settled science. But especially relevant for today is preserving vaccine choice. ACIP recommendations do not require anyone to get vaccinated, but they do provide the of insurance coverage, which is critical in allowing Americans to access vaccines.

[3:59:14]
In eliminating recommendations, you are threatening coverage and essentially removing choice for people who want to get vaccinated to protect their families, themselves, and their communities. Confusing, competing recommendations will only increase vaccine-preventable diseases. The risks here are not theoretical. They are painfully real. Children and adults alike will become sick and die, and from these serious illnesses. Disregarding these facts alone, along with public health expertise, is unacceptable. I implore you to recognize that maintaining the integrity of our nation's vaccine infrastructure is critical to doing so.
[Martin Kulldorff]

[4:00:00]
Thank you. And next, Nikki Carelli, please.
[Speaker 22]
Thank you so much. Thanks for the opportunity to speak with you today. My name is Nikki Carelli, and I am Executive Director of the Coalition to Stop Flu. We are a multi-sector federal advocacy coalition dedicated to ending deaths from seasonal and pandemic influenza. Our members represent a unified voice for the influenza ecosystem and include public health and patient advocacy organizations, academic, scientific, and research organizations, healthcare professional organizations, emerging biotech companies, healthcare distributors, and vaccine, antiviral, and diagnostic manufacturers. Our coalition was created because flu is one of our country's most predictable, preventable public health crises. Dr. Fulgati presented this morning on the extraordinary annual burden of flu, which includes not only tens of thousands of deaths, but hundreds of thousands of hospitalizations and millions of illnesses. Multiple researchers have estimated that flu costs our country billions of dollars a year in direct and indirect costs.

[4:01:01]
When we speak about flu, we speak about the continuum of prevention, diagnosis, and treatment. Although all three components are critically important, flu vaccination is broadly cited by physicians and public health agencies as the best way to reduce the risk of becoming infected with flu and any of its potentially serious complications. The flu vaccine has been administered to billions of people worldwide over decades and has an exceptionally strong safety record, making it one of the most well-studied and trusted tools in modern public health. ACIP's recommendation for annual flu vaccination for all Americans over six months of age without contraindications is critical to preserving access for the more than 100 million Americans who made the choice to get the flu shot last year. One of the most frustrating phrases that those of us in the influenza community often hear is, it's just the flu. Dr. Dukin noted this morning the record number of pediatric deaths this season. 250 deaths breaks the record that we broke only last year for the number of pediatric deaths in a non-pandemic year.

[4:02:02]
And also breaking records, 90 percent of those children were unvaccinated, up from 80 percent in prior years. That's 250 families with a missing seat at the dinner table that they will mourn every night for the rest of their lives. Pediatric influenza deaths were the genesis of the influenza recommendation that we have today, and they are exactly why we must stay the course. As you all know, ACIP does not set requirements. Instead, you serve a vital role as an aggregator and interpreter of evidence-based data. And perhaps most critically, your recommendations are directly tied to insurance coverage. The current influenza recommendation preserves access for hundreds of millions of Americans and ensures that patients who choose to be vaccinated can get their shot in a convenient setting. And most importantly, it saves lives. Thank you for taking on this incredibly important role, and the coalition looks forward to working with you to help restore public trust and confidence in vaccines.
[Martin Kulldorff]
Thank you for that. The next is Ronald Owens, please.
[Ronald Owens]

[4:03:03]
I was the California Department of Public Health employee between 2009 and 2023. On April 14, 2022, Department of Health and Human Services Secretary Javier Becerra said this about COVID-19 vaccines. Quote, we know that vaccines are killing people of color, Blacks, Latinos, Indigenous people at about two times the rate of white Americans. As a Black man who loves all humanity, this concerned me. On April 18, 2022, I emailed Deputy Director Becerra said, indicated various data about allergic reactions, facial paralysis, miscarriages, heart attacks, heart inflammation, seizures, strokes, and sudden deaths, plus stated there were 26,976 COVID-19 vaccine deaths. On October 13, 2022, I informed Deputy Director there were 31,330 deaths.

[4:04:01]
Californians were told COVID-19 vaccines are, quote, safe and effective. That is a lie. I prematurely retired so state public health officials could not muzzle truth from the public. Since then, I emailed COVID-19 vaccine warning written notifications to 58 California border supervisors, totaling 296 county elected and 62 administratively appointed local officials. I urged them to direct county health officers to start promoting, administering, and distributing COVID-19 vaccines. I would not have rode on my motorcycle more than 9,000 miles, urged 39 county border supervisors to stop the shots, and informed the California border pharmacy if I was not convinced that COVID-19 vaccines are killing people. Yesterday, I listened to subject matter experts assure the public that COVID-19 vaccines are safe and effective. Have they reached out and talked to any vaccine injured?

[4:05:02]
There are millions. I can introduce you to at least four. Shelly, Julie, Lori, Tanya. They shared their pain and suffering and they stopped the shots based on X every night from 9 p.m. to midnight Eastern time. How about an ACIP COVID-19 vaccine victims listening tour? We will help coordinate. People are suffering. People are dying. The government urged them to take the COVID-19 vaccines and now the government has completely abandoned them. Please do not ignore pain and suffering of your fellow citizens who were told COVID-19 vaccines are safe and effective. At minimum, federal health officials must inform Americans today that COVID-19 vaccines are killing people at an alarming rate.
[Martin Kulldorff]

[4:06:00]
Thank you. Next speaker is Catherine Varner-Perez.
[Kelly Goode]
Good morning. My name is Catherine Varner-Perez and I serve as the Director of Health Programs at the Alliance for Aging Research. Thank you for the opportunity to provide comments today. We have five recommendations. First, we urge ACIP to vote on COVID-19 vaccine recommendations as was stated in the federal register notice for this meeting. COVID-19 continues to pose a significant risk of severe illness, hospitalization, and death across the lifespan. Between the fall of 2023 and 2024, the CDC reported more than 36,000 deaths among adults 65 and older and 152 deaths in children. That's the equivalent of nearly 100 older adults dying each day and one child dying every two and a half days. The HHS Secretary's preemptive removal of COVID-19 vaccines from the recommended schedule for healthy pregnant people and children undermines ACIP's 50-year role of providing expert perspectives and advice on the use of vaccines in the U.S. population.

[4:07:14]
This decision also contradicts the FDA's newly published framework, which recognizes pregnancy as a high-risk condition. And because of this change, the American Pharmacists Association has withheld its endorsement of the current schedule. Second, we strongly urge the CDC to finalize ACIP's April vote on RSV. That vote would lower the age for risk-based recommendations for the RSV vaccine to include adults aged 50 to 59. RSV causes 42,000 hospitalizations annually in adults 50 to 64, and over 13 million adults in this age group have conditions that increase their risk of severe RSV. This change would save lives and reduce healthcare costs.

[4:08:00]
Third, please reinstate the vote on influenza vaccines for this year's strain that was promised at the April meeting. Otherwise, CMS and insurers will not cover them. Fourth, while we're grateful to see the approved vote on RSV for the Vaccines for Children program, we ask that ACIP restore all originally planned votes, including for COVID-19, HPV, and influenza. Without these votes, there's no guarantee of free vaccines for children who need them this fall. Finally, we strongly oppose any vote on the Marisol-containing influenza vaccines. The FDA has long confirmed the Marisol safety record, and it's only used as a preservative in multi-dosed adult flu vaccines to prevent bacterial and fungal growth. Removing it would disproportionately harm resource-constrained settings like nursing homes and long-term care facilities that serve older adults and rely on MDVs. More broadly, this discussion will unnecessarily sow doubt on vaccines. While the Alliance opposed the Secretary's decision to fire all 17 previous ACIP members, we now look to you to fulfill this critical responsibility.

[4:09:05]
We urge you to prioritize scientific integrity and impartiality as ACIP has done for 50 years. The health of the American people is in your hands.
[Molly Howell]
Thank you.
[Martin Kulldorff]
Thank you. And next is Allison Howells. Hello.
[Molly Howell]
I am Allison Howells, and I am the communications coordinator at Vaccinate Your Family. Thank you for giving me the opportunity to speak today. Vaccinate Your Family is a nonpartisan organization dedicated to saving lives from vaccine-preventable diseases. For more than 30 years, we have relied on ACIP recommendations to guide our work in educating the public. For our organization, preventing unnecessary death from disease is personal. In 2009, our colleague, Cerise Morata, lost her healthy 5-year-old son, Joseph, to flu. Our organization works closely with parents and family members who have lost loved ones or suffered consequences from vaccine-preventable diseases.

[4:10:02]
We honor the memories of Kimberly and Emily, young women who died from meningococcal B virus just a few years before a vaccine was available. Callie, Carter, Bree, and Brady, who died as infants from whooping cough before a vaccine for pregnant women became widely available. Teresa, a 10-year-old who lost her life to COVID one month before a vaccine became available for kids. We strive every day to stop suffering from diseases like these, as well as Hib, varicella, RSV, hepatitis, measles, shingles, and more. These are just a few of the personal stories we honor today. There are sadly many, many more, and there will be many more stories like this if access to lifesaving vaccines is compromised due to changes in recommendations that affect insurance coverage or cause confusion amongst providers and the public. We will be watching to understand how the members handle their new responsibility to protect the American people and keep America healthy.

[4:11:00]
We call on HHS and CDC to ensure that committee members avoid cherry-picking of data in order to draw conclusions that fit any previously conceived notions about vaccine safety. We hope to see members set aside personal beliefs and ideologies and base their conclusions and recommendations on the preponderance of available credible scientific data. Following the National Academy of Sciences review of the childhood and adolescent vaccination schedule, they concluded that vaccines are among the most safe and effective public health interventions to prevent serious disease and death. If access to lifesaving vaccines is compromised in any way, more children, adolescents, and adults will die. More people will suffer needlessly from preventable diseases. More families will be devastated by preventable tragedies as Americans become needlessly ill from diseases that decades ago crippled public health. We need only to look to history to see what will befall us if vaccines are no longer a part of preventative health care.

[4:12:03]
Vaccines need to remain available, accessible, and affordable. Lives depend on it. Thank you.
[Martin Kulldorff]
Thank you so much. The next speaker is Abraham Self, please.
[Abraham Self]
Can you hear me? Can you hear me?
[Martin Kulldorff]
Yes.
[Abraham Self]
By the grace of God, Secretary Kennedy, CDC leadership, Chairman Kulldorff, and members of the ACIP panel, thank you for the opportunity to speak. My name is Abraham Self, and I come to you today not as a scientist, but as a father who lost his child, not to illness, but to a system that misunderstood your guidance. Years ago, during a custody dispute, I expressed concern about the Gardasil vaccine, not out of neglect, but out of sincere beliefs and a desire to protect my child, and who did not want his child to become the next Colton from Utah.

[4:13:02]
That position led to an order of protection in the family court. The charges were eventually dropped, but the damage was done. The relationship with my son was severed, not by violence or abandonment, but by the unintended legal consequences of a medical recommendation. And I'm far from alone. Across the country, thousands of well-meaning moms and dads have been sidelined by family courts and child protection systems that treat ACIP recommendations as if they were mandates. A question, a hesitation, or a delay has too often been used as grounds to accuse a parent of being unfit. I want to be clear, neither the current members of this panel nor the previous ones caused this problem. ACIP has always been made up of individuals acting with integrity, compassion, and a genuine commitment to public health. But your work has been hijacked, not by you, but by courts, agencies, and individuals who use your recommendations as blunt legal instruments. And while you didn't cause this misuse, with deliberation and sensitivity, you have a unique opportunity to help correct it.

[4:14:06]
I sometimes wonder aloud, could there be broader systemic incentives, financial, bureaucratic, or even ideological, that benefit when families fall apart? I don't pretend to know the answer, but I do know this. When well-intended medical guidance is stripped of its nuance, real families suffer. That's why I'm here, not to accuse, but to ask. I respectfully urge this committee to consider including a clear disclaimer on all vaccine recommendations, that ACIP recommendations are expert guidance, not mandates, and that a parent's choice not to follow them, in part or in full, should not be used in isolation to question parental fitness or justify legal action. I've drafted sample language that I believe is brief, balanced, and helpful. It is available at tinyurl.com slash ACIP disclaimer. Again, that's tinyurl.com slash ACIP disclaimer.

[4:15:01]
And I humbly welcome your consideration. Thank you again for your time, your work, and your unwavering dedication to the well-being of children, parents, and the nuclear family unit. I believe we can work together to ensure that your voice continues to guide, not divide, the lives of those who trust in it. Thank you, and may God bless you all.
[Martin Kulldorff]
Thank you very much for those comments. The next speaker is Paula Ballester.
[Unknown]
Good afternoon. My name is Dr. Paula Ballester. I'm a double board certified pediatrician, a practicing pediatric hospitalist, and a mother to an amazing 12-year-old son. For over 15 years, I've had the privilege of caring for children during some of the most critical moments in their lives. I have seen the destruction that vaccine-preventable diseases can cause firsthand. Our dedicated team has treated patients who are neurologically devastated by meningitis, healthy children on life support from influenza, babies gasping for air from pertussis.

[4:16:03]
While the volume of these cases remains small, thanks entirely to the success of routine childhood immunizations, the rare cases we do see are almost exclusively in parents that were — in patients that were not vaccinated. My dreams have been haunted by the guttural screams of parents that have just lost their child and they're desperate, please, to turn back time and accept a vaccine that could have given their child a chance to grow up. Vaccines are arguably the greatest achievement in public health in our lifetime, preventing four to five million deaths per year globally. The ACIP has helped guide every major U.S. vaccine recommendation since 1964. Historically, it was comprised of leading experts under strict conflict of interest and transparency rules to keep the process focused on safety and evidence. Today is a sad day, as our current administration has chosen to gut those existing standards, a decision that could claim countless lives if the newest appointees choose to let propaganda and conspiracy theory guide decisions, rather than decades of vetted science and expertise.

[4:17:11]
I understand that parents are scared and overwhelmed. There is so much information out there, some of it false and some of it deliberately misleading. But here is what has not changed, the data. Tens of thousands of patients studied, including with placebo-controlled trials, spanning many countries and scientists, with consistently replicated results all validated by rigorous peer review. Childhood vaccines are safe and effective. Parents have every right to ask questions. It's OK to be cautious when it comes to your child. They're your world. And as a mother, I know this. But please trust trustworthy people who are trained to weigh risks and benefits, not the ones repeating conspiracy theories. Talk to your pediatrician. They have spent their entire careers to understand how to help protect your children and help them grow to their fullest potential.

[4:18:07]
We have always been here for you, and we always will be. To the ACIP, now is not the time to step back from science. It's time to stand tall and lead. I urge this body to have the courage to follow the evidence. Vaccines are not political. They are not about propaganda, power, or control. They are about protection of our children, our communities, and our shared future. You will be responsible for the loss of life if you walk back accepted immunization schedules and limit access to vaccines. Thank you for your time.
[Martin Kulldorff]
Thank you. And the next speaker is Christine Martin. Please.
[Speaker 15]
Good morning. My name is Dr. Christine Martin. I'm a board-certified pediatrician with over 30 years of pediatric primary care and public health experience. I, like my predecessor in the previous speech, am advocating for vaccines.

[4:19:05]
I have always been a fierce advocate for my patients and their families, but today I'm here on behalf of all pediatricians, pediatric nurse practitioners, and family practice providers who firmly believe in the value, efficacy, and safety of vaccines. In the course of my long career, I've personally seen children suffering from vaccine-preventable diseases. However, I've also witnessed dramatic decreases and near absence of some diseases due to the introduction and routine use of the pneumococcal, H flu, and meningitis vaccines. I've also seen the benefit of boosters of MMR, Varicella, and DTaP and Tdap. Finally, in the past years, I've had, for the first time in my career, tools to protect newborns and young infants from severe RSV disease. My exposure to vaccine-preventable disease and the harm and permanent disability they can cause came very early in life. One of my older brothers was deaf, and although he was not born deaf, many of his friends and classmates were due to congenital Rubella syndrome, a condition whereby a pregnant woman who contracts the disease passes it on to her fetus.

[4:20:07]
An infection leads to a wide range of birth defects, including sensorineural hearing loss or profound deafness. Rubella is now a vaccine-preventable disease thanks to the MMR vaccine, which was developed in 1971. And since the routine implementation of that vaccine, the incidence of Rubella and congenital Rubella have decreased so drastically that I, in my career, have never seen a case of it. I graduated from college and went into the Peace Corps in South America, where I saw unvaccinated children with mumps, whooping cough, and adults permanently disabled and paralyzed by polio. I also saw infants die from whooping cough and pneumococcal pneumonia. And I also saw vaccine-preventable diseases in my training in medical school and in residency at UCSF. As a medical student at UCSF, I had to take care of a baby with pneumococcal meningitis. And I'll never forget the 13-year-old girl who was brought in by her mom to San Francisco General ER with a fever and headache.

[4:21:06]
And within 20 minutes, she was in septic shock. And if she had not been in that ER, she would have died from meningitis. Currently, vaccines are a dam that prevents, is the best tool available, and prevents children and infants from vaccine-preventable diseases. And vaccines are the greatest public health achievement of the 20th century. Unfortunately, that dam is now cracks and fissures due to misinformation and public fear. At the present time, we are seeing the effect of that with the measles outbreak. If the cracks and holes continue to increase, the dam will fail, and we will start to see more and more cases of vaccine-preventable disease and the harmful effects of these diseases. Right now is the time to support and advocate for the routine vaccination schedule as is. These schedules were developed by experts, knowledgeable, highly qualified, and vetted scientists, researchers, and public health experts who are well-respected national experts on vaccines.

[4:22:10]
I, as a pediatrician, have dedicated my entire career to helping Caring for Children strongly endorse the current childhood vaccination schedules. And I implore you not to change them.
[Martin Kulldorff]
We're going to have to break here because the three minutes are way over. We have three more speakers that we want to make room for. And the next one is Elizabeth Hornbeck. Please go ahead.
[Elizabeth Hornbeck]
Hi, can you hear me?
[Martin Kulldorff]
Can you hear me? Yes, please go ahead.
[Elizabeth Hornbeck]
So my name is Elizabeth Hornbeck, and I'm a pediatric hospital hospitalist and mom of two wonderful boys. I really appreciate you giving me your time so I can speak to this committee today. I have no conflicts of interest to disclose, and my compensation is in no way tied to vaccination rates of my patients.

[4:23:00]
I want to start by stating that I respect the scientific background of the new ACIP committee since I myself have been almost entirely involved in clinical medicine since finishing training. I know the committee understands the data, and I know you will assess the risks and benefits of your recommendations very carefully. I am simply here to give you the perspective of a clinical practitioner and concerned parent. I have seen previously healthy children lose half of their lungs due to influenza. I've had to hug these parents while they cried and blame themselves for not getting the flu vaccine sooner. I've seen children, again previously healthy, neurologically devastated from influenza encephalitis. I have been unsure of how to answer the question, will they be OK, when I am transferring a baby to the PICU with RSV bronchiolitis. I try to reassure them that most do recover, but I am a person for whom honesty is a core value, and sometimes it is difficult to predict. This is not fear mongering. This is to give a backdrop to why I myself as a parent and a pediatrician vaccinate my children.

[4:24:04]
A lot of physicians will give arguments of we should love thyself as our neighbor as an argument to vaccinate kids due to more vulnerable populations and the benefits the herd immunity gives them. I like to think that I'm that selfless, but the truth is I'm not. My kids get vaccines because they're safe, and I am much more fearful of the harm that actual diseases can do. I vaccinate my kids first and foremost for selfish reasons, and thereafter for public health reasons. I encourage the ACIP members to continue with the previously recommended vaccine schedule. Vaccines need to be widely available, and to not recommend these vaccines affects insurance coverage and potentially in the future supply based on lack of insurance coverage. I fear the effect this would have on public health. The children of the United States are depending on you to do the right thing. I think we can all agree that the USA's strength is what makes our country so great.

[4:25:00]
Let's create strong kids through evidence-based vaccine recommendations so they have the ability to continue our country's legacy of strength. Thank you.
[Martin Kulldorff]
Thank you very much. And the next speaker is Neil Patel, please.
[Neil Patel]
Thank you. I would like to thank the committee for the opportunity to share my comments. I come here today as a general pediatrician and a new father whose day-to-day work involves providing well child care and answering questions about vaccines. I am the one families call in the middle of the night when they're worried their infant is having trouble breathing with RSV. I see nearly 1,000 newborn infants each year, and I'm often the first doctor these families meet. Ubiquitously, their first question is often when they can start protecting their newborn with vaccines. I felt obligated to take some time between my busy clinical schedule to share the most common concern that the families of my patients have been expressing to me. They are afraid that their children will no longer have access to life-saving vaccinations.

[4:26:00]
I served on the front lines during the COVID pandemic during my final year in residency. I was in the emergency room, the oncology units, and the pediatric intensive care unit. I saw teenagers placed on ventilators while their parents watched on video calls. Walking around the hospital, I still see shadows of colleagues lost during the pandemic. I'm heartbroken at the thought of those who would still be with us had the COVID vaccines been available sooner. I express my sincere gratitude to the scientists and former members of this committee whose work and recommendations on COVID vaccines saved countless lives during the pandemic. My message is simple. No child, no adult, no grandparent should be denied access to proven life-saving science. Vaccines eliminate disease. The recommendations of this committee determine the coverage of vaccines by insurance companies and critically by the Vaccines for Children's program. I can think of no public health intervention in this country that has been as effective as the Vaccines for Children program. As the new chair of this committee correctly repeatedly pointed out, the recommendations of this committee should adhere to evidence-based medicine.

[4:27:02]
Follow the science. Please continue to be transparent with the science. Just yesterday, materials that had been posted on the ACIP website were removed, specifically a CDC document on thimerosal-containing vaccines, which stated, to quote, considering the breadth of evidence and consistency and results from multiple population-based studies conducted in several countries with various study designs, the evidence does not support an association between thimerosal-containing vaccines and autism spectrum disorder or other neurodevelopmental disorders, close quote. I'm left to wonder why this document was removed from the website at some point yesterday. I hope that all members of this committee heed the creed of evidence-based medicine and protect access to life-saving vaccinations. Long COVID, the vertical transmission of hepatitis, HPV-associated cervical cancer, measles, and encephalitis all belong in history textbooks, not in our clinics, hospitals, schools, or homes. Thank you for your time.
[Martin Kulldorff]
Thank you, Dr. Patel. And our last speaker is Akshata Hopkins.

[4:28:01]
Please go ahead.
[Unknown]
Yes. Can you hear me?
[Martin Kulldorff]
Yes. Thank you.
[Unknown]
Okay. Yes. I'm Dr. Akshata Hopkins, a board-certified pediatric hospitalist where I care for some of the sickest children, those who require hospital-based treatment. But today I speak as a medical expert in children's health, a concerned parent of two incredible boys, and a citizen with a deep desire to protect our children, our families, and our communities. I still remember a 13-year-old boy who presented with high fever, rash, and lethargy. His spinal tap revealed pus. He was quickly diagnosed with Neisseria meningitis. A four-week-old infant diagnosed with pertussis, who repeatedly stopped breathing, what we call apnea, and later developed refractory and prolonged seizures. A previously healthy five-year-old girl hospitalized for 28 days with complicated haemophilus influenzae type B meningitis who suffered permanent hearing loss.

[4:29:03]
These are patients I vividly recall even now more than 15 years later. Why? Because these illnesses were preventable. In fact, thanks to vaccines, I haven't seen these diseases in over a decade. But here's what deeply concerns me. Many younger physicians have never been trained to recognize or manage these diseases simply because vaccines have made them so rare. If we weaken vaccine infrastructure or public confidence, we risk losing an entire generation of providers who will be caught unprepared. And more importantly, we risk children paying the price. In a world where we are advancing treatments and cures for complex pediatric conditions, it's alarming to think that we might slide backwards, watching children suffer or die from illnesses we know how to prevent. As a pediatrician, I have long relied on the ACIP's evidence-based recommendations to guide my clinical practice, support vaccine confidence, and promote equitable access to immunization services.

[4:30:05]
Vaccines are one of the most powerful tools we have in public health. But when the role of medical experts is diminished or worse, removed, and when science is politicized, everyone loses. Confusion grows, trust erodes, and preventable diseases like measles, meningitis, and pertussis return. I urge this committee and those who shape its future to protect the scientific integrity and expert-driven process that ACIP has always upheld. We may not all agree on every detail of every policy, but I hope we can agree on this. The health of our children deserves decisions led by evidence, not ideology. Thank you again for your service and for the opportunity to speak.
[Martin Kulldorff]
Thank you, and thank you to all the 13 speakers. We very much appreciate the receiving feedback from the public in this manner.

Brief Presentation on Anthrax Vaccine

[4:31:04]
We will now go to a five-minute presentation about anthrax vaccine, and that will be presented by Dr. Brendan Jackson at CDC.
[Speaker 30]
Great. Thanks so much. So, again, I'm Brendan Jackson of the Division of High Consequence Pathogens and Pathology. I'll be presenting a few slides to describe the intent to form an anthrax vaccine work group. Next slide, please. So, as a very brief background, Bacillus anthracis is the causative agent of anthrax and a spore-forming bacterium found naturally in soil around the world, including in some parts of the United States. Humans are most often infected by exposure to infected animals or animal byproducts through the cutaneous, gastrointestinal, or inhalational routes. However, B. anthracis is also a Tier 1 select agent due to its potential and past use as a bioweapon, its high case fatality rate, and ability to cause great harm to public health and safety, particularly when aerosolized.

[4:32:03]
Is the sound not working too well? It's okay? Okay, great. Next slide, please. We're proposing that the work group review a new vaccine called anthrax vaccine adsorbed adjuvanted, or AVAA, trade name Sifendis, which is a second-generation anthrax vaccine that includes the addition of an adjuvant. It was licensed by the FDA in July of 2023 for post-exposure prophylaxis following exposure to B. anthracis in adults aged 18 to 65. The anthrax vaccine work group intends to review the safety and immunogenicity of AVAA to develop recommendations for ACIP to consider for domestic use of this vaccine for anthrax post-exposure prophylaxis. That concludes my brief presentation. Thank you. Thank you so much, and thank you for making it brief.

Break

[Martin Kulldorff]
The next presentation is by myself about the MMRV vaccine, if we can have the slides.

[4:33:17]
No, the slides about the MMRV vaccine. We will take a five-minute break now, and we will be back at 12.25. So, thank you.

[4:41:30]
So, we will proceed now with the last half hour.

Resuming Meeting and Presentation on MMRV Vaccine

We will have a vote about the influenza vaccine, but just before that, we can have a short presentation about the MMRV vaccine, the measles, mumps, rubella, varicella vaccine. And I will be giving that presentation. So, next slide, please. So, the MMRV vaccine is one combined shot with one needle for measles, mumps, rubella, and varicella.

[4:42:05]
It was developed as an alternative to the MMR plus V, where you have two shots, one needle for measles, mumps, and rubella, and another from varicella. Between these two vaccines, there are no known differences in efficacy against either of these four diseases. Next slide, please. The timeline is that in 2005, the MMRV vaccine was licensed by FDA for children ages 12 months to 12 years of age. In 2006, this committee recommended the use of the MMRV with a preference over doing separate MMR and varicella vaccines. Next slide, please. The CDC's vaccine safety data link rapid cycle analysis. So, this shows the importance of the vaccine safety data link that CDC has.

[4:43:02]
We're monitoring this new vaccine with weekly data as it was rolled out. And for the first dose at age 12 to 13 months, there was a signal for an excess number of febrile seizures. That signal appeared after about 26,000 doses in the system. Next slide, please. So, at that time, there were 59 observed, 38 expected. And that was statistically significant to trigger a signal from these surveillance systems. Now, when you have a signal from a surveillance system, you then have to go to evaluate it. This could be because of data errors or a number of things. So, subsequently, there was a more thorough investigation about febrile seizures after this vaccine. Next slide, please. And you can see here that in the very bottom, there's sort of a random or fluctuation of febrile seizures occurring a different number of days after the vaccination.

[4:44:06]
So, there's sort of a background random noise here. But seven to 10 days after vaccination, there's a big peak of MMRV. There's also smaller peaks for the MMR vaccine, but it's a huge peak of excess febrile seizures seven to 10 days after receiving the MMRV vaccine. Next slide, please. So, a formal study looking at this found a relative risk of around two, which is about four to five excess febrile seizures per 10,000 children vaccinated. So, it's not huge, but it's not super rare either. And this was highly statistical significant. So, we know it's not a chance occurrence. MMR has an increased risk of febrile seizure compared to separate administration of the MMR and the varicella vaccines.

[4:45:01]
Next slide, please. This is consistent with there's also an excess risk of post-vaccination fever after the MMRV vaccine compared to the MMR and varicella. And this is all for children in the first dose, which is typically given at age 12 to 15 months. Next slide, please. There was a MMRV working group to look into this, and they made a vote out of four options. The old recommendation was both are recommended by the preference for the MMRV. In the working group, there was a vote that the majority thought it should be changed to both recommended with a preference for MMR plus V. There was a minority vote, both recommended with equal preference, and one vote to only recommend the MMR plus V. Next slide, please. When the ACIP met in June of 2009, there was a vote for the same issues, and then the majority was to have both recommended with equal preference.

[4:46:06]
A minority thought it should be a preference for MMR plus V. Next slide, please. So, ACIP, our committee is only advisory. It is the CDC who actually decides the recommendations. And in a very unusual situation, because usually CDC do follow the ACIP recommendation, but in this case, they did sort of an adjustment. So, they say, the CDC said that either MMRV or MMR plus V may be administered at this age, but for the first dose in children age 12 to 47, there's a preference for MMR plus V. Next slide, please. So, in summary, there's no known difference in the efficacy between these two options. After the first dose for children ages 12 to 23, there's very solid evidence-based evidence that there are more febrile seizures after MMRV than after MMR plus V, about one per 2,300 doses.

[4:47:10]
After the second dose of these vaccines at age 4 to 6 years, there's no excess risk for a febrile seizure. Next slide, please.

Proposed Recommendation on MMRV Vaccine

So, a proposed recommendation, we're not going to vote on that this time, but possibly at the next meeting, could be that as there exists a safer, equally effective alternative, the MMRV vaccine should not be administered to children under the age of 47 months. So, because of time constraint, I don't think we have time to have discussions of this, neither if we didn't have that for anthrax or shooting guinea either. So, we will leave this for a later meeting, and we will now proceed to the voting on the influenza vaccine.

Vote on Routine Annual Influenza Vaccination Recommendation

[4:48:05]
I will first read the first draft vote. Recommendations for influenza vaccination for the 2025 to 2026 season. ACIP reaffirms the recommendation for routine annual influenza vaccination for all persons ages greater or equal to 6 months who do not have contraindications.
[Robert Malone]
Malone, no conflict of interest. Make a motion to approve.
[Martin Kulldorff]
Thank you. Do we have a second? Yes. Thank you so much. So, we will then have a vote. So, please state your name, affiliation, and voting yes or no. And we'll start with the remote one this time. So, Dr. Meissner, please.
[Cody Meissner]

[4:49:02]
Cody Meissner, no conflicts. I vote yes. And I note there are very few contraindications to receiving the influenza vaccine. Thank you.
[Martin Kulldorff]
Thank you. Dr. Petchworth.
[Unknown]
Yes.
[Vicky Pebsworth]
You know, is it possible to abstain? Because we didn't discuss any of this during the meeting.
[Martin Kulldorff]
You may abstain. You can say your name and conflict of interest and abstain. That is a possibility, yes.
[Vicky Pebsworth]
Okay. My name is Vicki Petchworth, and I'm required to read the statement as it relates to conflict of interest as required in the CDC guidelines.
[Martin Kulldorff]
You don't need to read the statement. You don't need to read the statement. You have, that's okay. Thank you so much. Dr. Malone.
[Robert Malone]
Malone, no conflict of interest.

[4:50:00]
Yes.
[Joseph Hebelin]
Dr. Heberlin. Joseph Heberlin, no conflicts of interest. Yes. Dr. Levi. Reza Flevi, no conflict of interest. Yes.
[Martin Kulldorff]
Dr. Pagano. James Pagano, no conflicts of interest. Yes. And I am Martin Kulldorff, no conflict of interest. I also vote yes. So we have a vote for six yes and one abstain.

Vote on Thimerosal-Free Influenza Vaccine for Children

We will now go on to the vote concerning the Femarazole, and the first vote is for children, and I will read the statement first. ACIP recommends children 18 years and younger receive seasonal influenza vaccine only in single-dose formulations that are free of Femarazole as a preservative. So again, please state your name, conflict of interest, and your vote. We can start with Dr. Levi this time.
[Retef Levy]

[4:51:01]
Reza Flevi, no conflict of interest.
[Martin Kulldorff]
Yes. Dr. Pagano. James Pagano, no conflicts of interest. Yes. Dr. Heberlin.
[Joseph Hebelin]
Dr. Heberlin, point of order. Do we need a motion and a second? Oh, sorry.
[Robert Malone]
I'm sorry.
[Joseph Hebelin]
Do we have a motion?
[Robert Malone]
So moved by Malone. Do we have a second?
[Cody Meissner]
Second from Meisner.
[Martin Kulldorff]
So we start over. I'm sorry. Reza Flevi, no conflict of interest.
[Joseph Hebelin]
Dr. Pagano. Pagano, no conflicts of interest. Yes. Dr. Heberlin. Joseph Heberlin, no conflicts of interest. Yes. Dr. Malone.
[Robert Malone]
Malone, no conflict of interest. Yes. Dr. Petsworth.
[Martin Kulldorff]

[4:52:01]
Vicky. We'll go to Dr. Meisner.
[Cody Meissner]
Can I ask, will we have an opportunity to explain our vote?
[Martin Kulldorff]
Yeah, if you vote first, you can explain afterwards. Thank you.
[Cody Meissner]
I vote no. Meisner, no conflict.
[Martin Kulldorff]
Dr. Petsworth. We have no response there. My name is Martin Kulldorff, no conflict of interest. I vote yes. So we have a vote of five yes, one no, and one person not able to, we lost contact with one person. We'll go to the next portion.

[4:53:07]
Dr. Petsworth.
[Molly Howell]
Oh, it is now working. I'm sorry, it wasn't working.
[Vicky Pebsworth]
I would like to abstain from that vote, please.
[Martin Kulldorff]
Okay. So we have, can you state your name and conflict of interest, that you don't have conflict of interest?
[Vicky Pebsworth]
I'm Vicky Petsworth, and I have the statement that- You don't have to read the statement.
[Martin Kulldorff]
You just have to say that you have no conflict or, yeah. Okay, that's good.
[Vicky Pebsworth]
I'm allowed to participate.

Vote on Thimerosal-Free Influenza Vaccine for Pregnant Women

[Martin Kulldorff]
So we go to the next vote. So I'll read it first. ACIP recommends pregnant women receive seasonal influenza vaccines only in single-dose formulations that are free of femorisol astropreservative. Do we have a motion? So moved, Malone. Do we have a second? Second, Meisner. Thank you.

[4:54:00]
And we'll start with the vote. Dr. Malone.
[Robert Malone]
Malone, no COI, no conflict of interest.
[Joseph Hebelin]
I apologize. Yes. Dr. Heblon. Joseph Heblon, no conflicts of interest. Yes. Dr. Pagano. Pagano, no conflicts of interest. Yes. Dr. Levi.
[Retef Levy]
Rtsev Levy, no conflict of interest. Yes. Dr. Petsworth.
[Vicky Pebsworth]
Vicky Petsworth, no conflicts in this case, and abstain.
[Cody Meissner]
Dr. Meisner.
[Martin Kulldorff]
Cody Meisner, no conflicts, and I vote no. And I'm Martin Kulldorff, no conflicts of interest. I vote yes. So we have five votes yes, one no, and one abstain.

Vote on Thimerosal-Free Influenza Vaccine for All Adults

The last vote for today is, I'll read it first. ACIP recommends all adults receive seasonal influenza vaccine only in a single dose formulation that are free of thimerosal as a preservative.

[4:55:06]
Do we have a motion? Malone, so moved. Do we have a second? Meisner, second. Thank you. And we can start voting. Dr. Levi. Rtsev Levy, no conflict of interest. Yes.
[Joseph Hebelin]
Dr. Pagano.
[Martin Kulldorff]
Pagano, no conflicts of interest. Yes. Dr. Heblon.
[Joseph Hebelin]
Dr. Heblon, no conflicts of interest. Yes. Dr. Malone.
[Robert Malone]
Malone, no conflict of interest. Yes. Dr. Petzworth.
[Vicky Pebsworth]
Vicki Petzworth, no conflicts, abstain.
[Martin Kulldorff]
Dr. Meisner. Cody Meisner, no conflicts, no. And I'm Martin Kulldorff, no conflict of interest. Yes. So we have five yes votes, one no vote, and one abstain. And does anybody want to explain their vote?

Explanation of Votes

[4:56:00]
Dr. Levi.
[Retef Levy]
Yeah, I just want to share my hope that we can work with our colleagues at the CDC to develop better ways to, and more reliable ways to evaluate the efficacy of flu vaccines, broadly speaking, and the comparative, the relative efficacy of the different vaccines. I think we can, and hopefully can do a better, a more precise job. I know it's an untrivial task, but I think we need to work hard to bring to the public the most accurate scientific assessments of the efficacy of these vaccines.
[Joseph Hebelin]
Dr. Heblon. I wish to note that there is a significant benefit to the use of multi-dose vaccines instead of single-dose vaccines. And apparently there is good data that other preservatives can be used. So I hope that the committee will put on the agenda the consideration of multi-use vials rather than single-use vials that have other better preservatives.

[4:57:10]
Thank you. Dr. Malone.
[Robert Malone]
I wish to note regarding the recommendations for influenza vaccine for the season and the recommendation for routine annual influenza vaccination for all persons greater than or equal to six months. Lacking contraindications, I look forward to a robust evaluation in the subcommittee of the potential risks and benefits, relatively speaking, of the alternative products that are currently available on the market. And for, I anticipate there will be active consideration of the longstanding issue of immune imprinting and original antigenic sin, which may or may not be a concern in the case of routine annual influenza vaccination.

[4:58:09]
Over.
[Martin Kulldorff]
Any other comments from the members of the committee? Yes. Dr. Meissner. Yeah, thanks.
[Cody Meissner]
I would like to make the point that my concern is that by insisting the multidose vials contain thimerosal, that might limit the availability of the influenza vaccine for some people. I would like to have that question answered, but it's probably a difficult one to answer. My point is the risk from influenza is so much greater than the non-existent, as far as we know, risk from thimerosal. So, I would hate for a person not to receive the influenza vaccine because the only available preparation contains thimerosal.

[4:59:07]
I don't, I find that very hard to justify.
[Martin Kulldorff]
Over. Thank you. Dr. Petchworth.
[Vicky Pebsworth]
Yes, I wanted to say that I, my personal views on, on this is that we should not be doing anything that restricts access to vaccines of any sort, especially those that are already approved by the FDA and that are already in the schedule. My problem and the reason I abstained for all of these votes is because of the way the voting question was written. In the world of survey research, you don't ask two things in the same question. So, there's buried in this is a recommendation that all adults receive seasonal influenza and then the second part of it in formulations that are free of thimerosal as a preservative.

[5:00:01]
Yes, I think we should not be using thimerosal as a preservative, but we didn't get into any sort of a discussion about the first part of the question. So, I just, you know, in the future, when we're asked to vote on something, if we could just vote on one thing at a time, that would be helpful. Thank you.
[Martin Kulldorff]
Thank you for that comment. I think that we are almost done with this meeting. Before we conclude, I would like to thank, first of all, the public who has been listening to these interesting discussions about science, about medicine, about vaccines, and monoclonal antibodies. We really appreciate that, and that includes the public speakers, but I know there were many other people from the public who were listening in, and I thank you very much. I would also like to thank the CDC staff for very informative presentations.

[5:01:05]
There was a lot of work behind those, not only those people presenting, but other members of the CDC staff, and we're looking very much forward to continue to working with you as members of this committee. I also would like to thank the seven members of the committee who, at very short notice, have indulged in these issues, spending a lot of time and very thoughtfully thinking about it. And we are all on the same page here, that what is important is using evidence-based medicine to promote public health, and that we do that in an unbiased, open, transparent way, where we listen to various views and opinions, both from scientists but also from the public.

[5:02:07]
So, again, to everybody, I really appreciate your spending this one and a half day with us, so thank you very much.
[Cody Meissner]
Thank you very much. On your order, Mr. Chair. On your order. Martin, can I make a comment? Yes, please.

Comment on AAP Boycott

I would like to comment on the decision by the American Academy of Pediatrics to boycott this meeting. In the past, the AAP has been very helpful in generating recommendations, and I think it's somewhat childish for them not to appear. It's dialogue that leads to the best recommendations for the use of vaccines.

[5:03:02]
I mean, I'm led to think that they didn't want to come because they didn't want to have to support some of their decisions that are difficult to do. But in the future, I strongly recommend the American Academy of Pediatrics to participate in these meetings, as they always have.
[Martin Kulldorff]
Thank you. Thank you very much. And I will hereby conclude this meeting, and I hope you all have a wonderful afternoon.

Conclusion of Meeting

And thank you so much, everybody.
[Speaker 24]
Thank you.
[Neil Patel]
I'm sorry, Mr. Chair.
[Joseph Naima]

[5:04:06]
Oh, I was muted.