summary 2025 06 25 26 508

MEETING OF THE ADVISORY
COMMITTEE ON IMMUNIZATION
PRACTICES (ACIP)

J
UNE 25-26 , 2025
MEETING SUMMARY

Tr
ade names are used for identification purposes only and do not indicate endorsement.

2
 WEDNESDAY : JUNE  25, 2025

WELCOME AND I NTRODUCTIONS

C
all to Order/Roll Call

D
r. Martin Kulldorff, Chair of the ACIP, convened the meeting on June 25, 2025. He welcomed
the members, thanked the current and former committee members and CDC staff, and
emphasized the committee’s commitment to evidence- based vaccine recommendations. Dr.
Kulldorff stressed the importance of open scientific inquiry, rebuilding public trust, and addressing vaccine safety transparently to support public health.

D
r. Mina Zadeh (ACIP Executive Secretary, CDC) made opening announcements about the
availability of presentation slides on the ACIP website, the scheduled oral public session, and
the written public comment process. She reviewed conflict of interest polici es for ACIP
members. A list of Members, Ex Officios, and Liaison Representatives is included in the appendices at the end of this summary document. She welcomed the new committee members
who introduced themselves:  Dr. Martin Kulldorff, Dr. Joseph Hibbeln,  Dr. Retsef Levi, Dr.
Robert Malone, Dr. Cody Meissner, Dr. James Pagano, and Dr. Vicky Pebsworth. While no
conflicts of interest were identified for the first day of the meeting, Dr. Vicky Pebsworth disclosed
that she owns stock in a healthcare sector fund that includes holdings relevant to ACIP
discussions, including vaccine manufacturers. However, the value of this stock falls below the
Office of Government Ethics’ de minimis threshold. Dr. Pebsworth confirmed that she understood, and therefore, she is permitted to participate fully in the ACIP meeting.

UPDATE ON WORK GROUPS

D
r. Kulldorff emphasized the critical role of ACIP work groups, which are composed of national
experts who investigate vaccine- related issues and provide recommendations to the committee.
New chairs are being appointed to lead these groups, while many current members will continue their work to ensure continuity and progress. There are currently 11 active work groups focusing
on vaccines for chikungunya, COVID- 19, cytomegalovirus, HPV, influenza, meningococcal
disease, pneumococcal disease, and RSV. Dr. Kulldorff announced plans to establish new work
groups, including one to evaluate the cumulative childhood and adolescent vaccine schedules.
This group will assess potential interactions between vaccines, the total number of vaccines
administered, ingredient amounts, and the timing of administration. The National Academy of
Medicine has previously called for additional research in this area. Another new work group will
review vaccines that have not been formally reassessed in over seven years, a practice intended to be routine but not yet systematically implemented. Future topics for review may
include the timing of the hepatitis B birth dose, whether separate MMR and varicella vaccines
should be preferred over the combined MMRV due to seizure risks, and the possibility of
considering alternative MMR vaccines used in other countries. Dr. Kulldorff emphasized the
importance of collaboration, open scientific discussion, and a commitment to evidence -based
medicine in enhancing public health outcomes.

3
 COVID -19 VACCINES

D
r. Adam MacNeil (CDC/NCIRD) provided a recap to summarize events of the past year. Last
June, ACIP recommended the 2024– 2025 COVID -19 vaccination for all individuals aged 6
months and older. In August, the FDA authorized or approved Moderna, Pfizer, and N ovavax
COVID -19 vaccines, and in September, ACIP’s recommendations and CDC vaccination
guidance were published in the Morbidity and Mortality Weekly Report (MMWR).
At the October 2024 ACIP meeting, the committee recommended additional doses for adults
aged 65 and older and for individuals aged 6 months and older with moderate or severe
immunocompromise. These recommendations were published in the MMWR in December
2024. As has been customary following changes in recommendations, CDC updated its interim clinical considerations accordingly.
The CDC updated its recommendations in May 2025. Per HHS directive, guidance shifted to
shared clinical decision- making for healthy children aged 6 months through 17 years, and no
recommendation was provided for pregnant individuals. Also in May, the FDA approved Novavax’s NUVAXOVID (2024–2025 Formula) and Moderna’s MNEXSPIKE (2024– 2025
Formula) for individuals aged 12– 64 at high risk for severe COVID -19, and for all individuals
aged 65 and older.
On May 22, 2025, FDA’s Vaccines and Related Biological Products Advisory Committee
(VRBPAC) met to discuss strain selection for the 2025– 2026 COVID -19 vaccine formula. FDA
subsequently advised manufacturers to use a monovalent JN.1 -lineage- based antigen
composition, preferably the LP.8.1 strain.
Dr. MacNeil provided an overview of the current routine COVID -19 vaccine schedule by age
group. Children aged 6 months to 4 years who are unvaccinated may receive a multidose initial series with a 2024–2025 COVID -19 mRNA vaccine, using shared clinical decision -making.
Those who have previously completed an initial series may receive one dose of a 2024– 2025
mRNA vaccine from the same manufacturer, under shared clinical decision- making.
Individuals aged 5– 17 years may receive one age -appropriate dose of a 2024– 2025 COVID -19
vaccine using shared clinical decision- making. Adults aged 18–64 years should receive one
dose of any 2024– 2025 COVID -19 vaccine, while those aged 65 and older should receive two
doses of any 2024– 2025 COVID -19 vaccine, spaced six months apart.
The current recommendations for individuals with moderate or severe immunocompromise were
also reviewed. Those who are unvaccinated should receive a multidose vaccination series with an age- appropriate 2024 –2025 COVID -19 vaccine, followed by one additional  2024–2025
vaccine dose six months after completing the initial series.
Individuals who have previously completed an initial series should receive two doses of an age-
appropriate 2024– 2025 COVID -19 vaccine, spaced six months apart. Additional age-
appropriate 2024– 2025 COVID -19 vaccine doses may be administered under shared clinical
decision- making.
It was noted that COVID -19 vaccines have had interim recommendations since 2020,
developed with the understanding they would be revisited as new information became available.
In recent years, the work group explored non- universal recommendations, which would apply
only to specific age or risk groups. At the ACIP meetings in September 2023 and June 2024, the work group presented interpretation summaries outlining discussions on universal versus non -
universal policy options for the 2023– 2024 and 2024– 2025 vaccines, respectively.
4
 Based on the available evidence and implementation considerations, a universal
recommendation was ultimately supported. Since November 2024, the work group has
discussed recommendations for the 2025– 2026 season. At the April 2025 ACIP meeting,
members cons idered adopting a non -universal recommendation.
Dr. MacNeil summarized that between November 2024 and June 2025, the COVID -19 work
group reviewed epidemiology and disease burden, vaccine effectiveness, safety, and
implementation considerations. At the most recent work group meeting on June 5 and follow -up
polling, the group agreed on recommendation categories for the 2025– 2026 COVID -19
vaccines. These include age- appropriate vaccination for all infants and children aged 6– 23
months, as well as for individuals aged 2– 64 years who are at high risk for severe COVID -19
(including pregnant individuals), those at high risk of exposure, and those who desire additional protection under shared clinical decision- making. The group also supported a recommendation
for two doses of the 2025– 2026 COVID -19 vaccine for adults aged 65 and older, as well as for
individuals aged 6 months and older with moderate or severe immunocompromise.
Dr. Adam MacNeil (CDC/NCIRD) provided an update on the current epidemiology of COVID -19.
CDC estimates that since October 1, 2024, there have been between 9.8 and 16.1 million
COVID -19–associated illnesses, 2.4 to 3.8 million outpatient visits, 270,000 to 440,000
hospitalizations, and 32,000 to 51,000 deaths related to COVID -19.
Long COVID remains a significant public health concern. 2023 national surveys estimated that
approximately 9.2 million adults and 0.3 million children in the United States had long COVID.
Among adults, 3.6% reported current long COVID symptoms and 8.4% reported ever having
long COVID. Among children, 0.4% reported current symptoms, and 1.4% reported having the
condition at some point in their lives. More than three in five adults and nearly four in five children with long COVID reported experiencing activit y limitations due to their symptoms.
COVID -NET, a population- based surveillance system that monitors laboratory -confirmed
COVID -19–associated hospitalizations, was used for the presentation. It is part of the
Respiratory Virus Hospitalization Surveillance Network, along with RSV -NET and FluSurv -NET,
and includes >300 hospitals in 185 counties across 13 states. The surveillance area represents approximately 10% of the U.S. population. Hospitalizations are included if a positive COVID -19
test occurs within 14 days before admission or during hospitalization. Basic demographic data are collected for all patients, and detailed clinical data are gathered from a random sample
stratified by age and site. Seasons are defined in the presentation as July 2024– June 2025 for
rates, and clinical data reflect  the most recent 12 -month period, from April 2024 through March
2025.
COVID -19–associated hospitalization rates tend to peak both in the winter and the summer.
This pattern differs from RSV and influenza, which generally follow a more consistent seasonal trend with a single peak, typically in the winter. Cumulative COVID -19–associated
hospitalization rates for the July 2024– May 2025 period were higher during summer and fall
2024 and lower during the winter months compared to July 2023– June 2024. From July 2024 to
April 2025, a period that included a high severity influenza season, more infants <1 year and
adults ≥75 years of age had hospitalizations associated with COVID -19 than influenza.
Cumulative COVID- 19-associated hospitalization rates are highest among adults aged ≥75
years, followed by adults aged 65– 74 years and infants aged <6 months.
The weekly number of COVID -19–associated deaths reported to the CDC in the United States
from June 8, 2024, to June 7, 2025, showed a decreasing trend and remained low in the winter. Deaths during the winter were lower than those reported in the summer and fall of 2024. The
number of deaths with COVID -19 listed as the underlying cause of death from July 2024 to June
2025 showed that while COVID -19 causes deaths across all age groups, 70% occurred in
5
 adults aged 65 and older. Death certificate data likely underestimates COVID -19-associated
deaths. Among in- hospital deaths in patients with laboratory -confirmed SARS -CoV-2, the
proportion with a COVID -19 cause of death listed decreased from 95% in 2020 to  60% in 2022–
2023. CDC estimates that since October 1, 2024, between 32,000 and 51,000 people have died
in the United States from COVID -19.
The highest rates for COVID -19 in the New Vaccine Surveillance Network were observed in
infants <6 months of age.
More than half of pediatric COVID -19-associated hospitalizations in COVID -NET occur in
children aged <2 years. COVID -19 causes severe disease in infants younger than 6 months,
who have the highest rates of COVID -19–associated hospitalization among all pedi atric age
groups. During July 2024 to May 2025, the cumulative COVID -19–associated hospitalization
rate among infants was 268 per 100,000, comparable to the rate of 266 per 100,000 among
adults aged 65– 74 years. As noted earlier in the presentation, hospit alization rates are higher
among those aged >75 years and lower among those aged <65 years.
Among infants <6 months old who were recently hospitalized for COVID -19, 22% were admitted
to the ICU, 71% had no underlying medical conditions, and only 3.5% had any record of
maternal COVID -19 vaccination during pregnancy. No COVID -19 vaccine products ar e
approved for use in infants <6 months, so any protection must come from transfer of maternal
antibodies, either from vaccination during pregnancy or prior infection.
Among vaccine- eligible children and adolescents ages 6 months –17 years, 41% of COVID -19-
associated hospitalizations occurred among children ages 6– 23 months.COVID -19-associated
cumulative hospitalization rates are highest among the youngest age groups. The  youngest age
groups have comparable rates of cumulative COVID -19-associated hospitalization to some
adult age groups, but direct comparisons are challenging. While most adults aged 50– 64 years
admitted for COVID -19 had underlying medical conditions, more than half of children aged 6– 23
months were otherwise healthy prior to their COVID -19 hospitalization.
Among children aged 6– 23 months hospitalized for COVID -19, 54% had no underlying medical
conditions. Among those with an underlying condition, the most common was prematurity. In the three older pediatric age groups (ages 2– 17 years), >70% of hospitalized children and
adolescents had at least one underlying condition, with asthma or reactive airway disease and neurologic disorders being the most common. The proportion of hospitalized children with no
underlying medical conditions decreases with increasing age.
One in four children aged <18 years hospitalized for COVID -19 required ICU admission. Among
children <2 years who were admitted to the ICU, the majority (53%) had no underlying medical conditions. 89% of COVID -19 vaccine- eligible children and adolescents w ho were hospitalized
with COVID -19 had no record of receiving the most recent recommended COVID -19 vaccines.
From July 2024 to June 2025, the number of COVID -19–associated deaths among children <2
years was similar to the number of influenza- associated deaths. Among children aged 2– 17
years, influenza- associated deaths were higher. COVID -19 deaths are likely underestimated, as
pediatric flu deaths were nationally notifiable during this period, while pediatric COVID -19
deaths were not.
Since March 2020, 128 COVID -19–associated deaths among children and adolescents have
occurred within the COVID -NET catchment area, either during hospitalization or within 30 days
after discharge. Of the 25 pediatric deaths reported since July 2023, 10 occurred during the
most recent 12- month period from April 2024 through March 2025. These are raw counts, and
the COVID -NET catchment area represents approximately 10% of the U.S. population.
6
 Among the 25 deaths since July 2023, 52% were in children <2 years, and 72% had at least
one underlying condition. Of the 16 children eligible for COVID -19 vaccination, 14 had no
vaccination record, and none were up to date. Death certificate data reporting to COVID -NET is
delayed. Among the 25 most recent deaths with complete mortality data, 28% had COVID -19
listed as a specific cause of death, while an additional nine deaths were attributed to other
respiratory or circulatory causes.
Dr. MacNeil summarized that most pediatric COVID -19 hospitalizations occur in children <2
years old, and many of these children have no underlying medical conditions, including 71% of
infants <6 months and 54% of children aged 6– 23 months. Hospitalization rates are highest
among infants <6 months, followed by those aged 6– 23 months. Rates among infants <6
months of age are comparable to those of adults aged 65– 74 years. No COVID -19 vaccine
products are approved for infants <6 months, so any protection must come from maternal
antibody transfer through vaccination during pregnancy or prior infection.  Outcomes among
hospitalized children can be severe, with 1 in 4 admitted to the ICU. COVID -19–associated
deaths continue to occur among infants and children, and the majority of hospitalized, vaccine -
eligible children and adolescents had no record of receiving the most recently recommended
vaccine.
Adults ages ≥65 years comprise more than 2/3 of all COVID -19–associated hospitalizations
among adults. Most adults hospitalized for COVID -19 have ≥1 underlying medical condition; a
majority have ≥2. Among adults hospitalized for COVID -19, 15% were admitted to the intensive
care unit (ICU). During this period, 85% of all adults hospitalized with COVID -19 who died in -
hospital were ages ≥65 years.
Moving to COVID -19 hospitalizations among adults. Among adults hospitalized for COVID -19
from October 2024 through March 2025, vaccination status varied by age group. For adults
aged 65 years or older hospitalized for COVID -19, 65% had received neither the 2023– 2024 nor
the 2024– 2025 COVID -19 vaccine. One -third of the patients had received at least one dose of
the 2024– 2025 vaccine before admission, and 17% had received two doses.
Pregnancy status was collected for women aged 15– 49 years who were hospitalized with a
laboratory -confirmed SARS -CoV-2 infection. Of those hospitalized, 28.5% were pregnant, and
50% of these had COVID -19-related signs or symptoms. Among 131 hospitalized pr egnant
women with confirmed infection and symptoms, 50% had no underlying medical conditions. At
discharge, 68% were no longer pregnant. Among these, 83% had a healthy newborn, 11% had
a preterm birth, 1% had an ill infant,  and 5% experienced pregnancy loss. Vaccination
coverage was low, with 92% having no record of receiving a COVID -19 vaccine since July 1,
2023, and only 5.8% having received a recommended 2024– 2025 COVID -19 vaccine dose.
Dr. MacNeil summarized the adult data by noting that rates of COVID -19–associated
hospitalization are highest among the oldest adult age groups. Adults aged ≥65 years
accounted for 72% of adult COVID -19—associated hospitalizations, and those aged ≥75 years
made up 50%. Although hospitalization rates have decreased over time, cumulative rates
among adults aged 75 years and older remain high. The risk of COVID -19–associated
hospitalization continues year -round, with peaks in both winter and summer.
Among adults aged ≥65 years hospitalized with COVID -19, 65% had no record of receiving one
or more doses of the recommended 2024– 2025 COVID -19 vaccine before admission. Most
adults hospitalized for COVID -19 had at least one underlying medical condition, and the majority
had two or more.
7
 Among SARS- CoV-2-positive pregnant women admitted from April 2024 to March 2025 with
COVID -19–related symptoms at admission, half had no underlying medical conditions, and 92%
had no record of COVID -19 vaccination since July 1, 2023.
The last part of the epidemiology presentation was on SARS -CoV-2 genomics. Since SARS -
CoV-2 emerged in late 2019, the virus has continued to evolve with accumulating substitutions
in the spike protein, which binds to the ACE2 receptor and is the main target for neutralizing
antibodies. Over time, there have been periods of gradual genetic drift as well as more
significant shifts when new lineages emerged with numerous changes.
The first major shift occurred in late 2021 to early 2022, with the transition from the Delta variant
to Omicron. Subsequent shifts included the emergence of XBB lineages from BA.4 and BA.5
viruses, and more recently from XBB to JN.1. These shifts necessit ated updates to the COVID -
19 vaccine formulation to ensure continued protection.
In winter 2023 -2024, we observed a strain replacement of XBB.1.5 -like viruses to JN.1 -like
viruses. Since the emergence of JN.1, SARS -CoV-2 lineages have continued to evolve from this
variant, but no complete strain replacement has been observed. All lineages that have predominated since the emergence of JN.1 are currently descendants of JN.1.
LP.8.1, XFC, and NB.1.8.1 are JN.1 lineage viruses. When comparing amino acid substitutions
in the spike protein to the 2024– 2025 COVID -19 vaccine formulation, there are only 2 to 4
changes in the receptor binding domain. In contrast, circulating viruses l ast summer had 13 or
more changes in the spike receptor binding domain compared to the vaccine formulation at that time.
Dr. MacNeil summarized that current circulating SARS -CoV-2 viruses are descendants of JN.1,
with 2 to 3 substitutions in the spike receptor binding domain compared to the KP.2 spike.
These viruses are effectively neutralized by serum from individuals who r eceived the 2024–
2025 COVID -19 vaccine. Antigenic cartography shows that JN.1 viruses are antigenically
similar. In May 2025, FDA’s VRBPAC reviewed genomic and phenotypic data and unanimously
recommended a monovalent JN.1 -lineage vaccine for the 2025– 2026 vaccine. FDA has advised
manufacturers to use a JN.1- based vaccine, preferentially using the LP.8.1 strain.
Dr. Adam MacNeil (CDC/NCIRD) provided an update on vaccine effectiveness. For respiratory viruses, the CDC primarily uses case -control studies, including the test -negative design (TND),
to measure vaccine effectiveness (VE). In the TND, individuals seeking care for respiratory
illness are included. Cases are those who test positive for SARS -CoV-2, and controls are those
who test negative.
Controls represent the population from which cases arise and help estimate COVID -19 vaccine
coverage among people seeking care for respiratory illness. By comparing vaccination status
between cases and controls, we determine VE. Higher vaccine coverage among controls
suggests the vaccine provides protection. Because both groups sought care for similar
symptoms, this design helps reduce confounding factors, such as age and geography, thereby
clarifying the relationship between vaccination and illness.
VE results were shared from three CDC platforms. The VISION Network, one of the platforms,
encompasses data from over 300 emergency departments (ED) and urgent care (UC) clinics, as
well as more than 200 hospitals nationwide. It uses a test -negative design  to evaluate VE
among individuals of all ages with COVID -19–like illness. Cases tested positive for SARS -CoV-
2 and did not positive for RSV or influenza. Controls tested negative for SARS -CoV-2 did not
test positive for influenza or RSV, depending on age. Vaccination status is confirmed through
electronic health records and immunization registries.
8
 The second VE platform, the Overcoming COVID -19 Network, focuses on children, with
enrollment at 26 pediatric hospitals across 20 states. The analysis presented assessed the
effectiveness of COVID -19 vaccination during pregnancy in preventing COVID -19–related
hospitalizations in infants under 6 months of age.
The third VE platform, the IVY Network, includes 26 hospitals across 20 states. Like VISION,
IVY uses a test -negative design but with active enrollment, including patient interviews and
nasal swabs. The analysis focused on adults aged ≥18 years hospitalized with COVID -19–like
illness. Cases tested positive for SARS -CoV-2, while controls tested negative for SARS -CoV-2,
influenza, and RSV. Vaccination history was determined through medical records, registries,
and plausible self -report, with specimens collect ed for central testing and sequencing.
COVID -19 VE measurement approaches have evolved over the years. Initially, absolute VE was
used to compare outcomes in vaccinated versus unvaccinated individuals. During the bivalent
vaccine era, relative VE was also measured, comparing outcomes between di fferent vaccine
types (e.g., bivalent vs. original monovalent). For the 2023– 24 and 2024– 25 COVID -19
vaccines, VE estimates combine both approaches by comparing disease frequency in
individuals who received the current vaccine with that in individuals who did not, regardless of
their prior vaccination or infection history. This method aligns with how seasonal influenza VE is
measured and reflects the added benefit of annual vaccination.
COVID -19 vaccination coverage in children remained low during both the 2023– 24 and 2024–
25 seasons. Coverage was similar across both years, with the lowest rates observed among
children aged 6 months to 4 years in the 2024– 25 season.
COVID -19 vaccine uptake among adults aged ≥18 years was just under 25% by the end of
August 2024 for the 2023- 2024 vaccine and the end of April 2025 for the 2024- 2025 vaccine.
Coverage for the 2024– 2025 vaccine began increasing slightly earlier due to earl ier
recommendations and availability, but reached a similar overall level to 2023- 2024 coverage by
the end of April 2025.
Among Medicare fee -for-service beneficiaries aged ≥65 years, overall COVID -19 vaccination
coverage for the 2024– 25 season reached 28% by January 2025. Coverage was highest in
beneficiaries with immunocompromising conditions (32%) and lowest in those without
underlying medical conditions (24%).
For the 2023– 24 season, COVID -19 VE against ED and UC visits was evaluated through
August 2024 in VISION. The reference group included individuals who did not receive a 2023–
24 vaccine. For those aged ≥5 years, this included unvaccinated individuals and those who had
only received monovalent or bivalent doses. For children aged <5 years, both vaccinated and
comparison groups had to complete an initial series. VE was generally comparable across age
groups, with estimates for children being similar or higher than those for adults, consistent with
trends observed in previous seasons.
For the 2024– 25 season, COVID -19 VE against ED and UC visits was assessed for the 7 to 179
days post -vaccination period in VISION. Due to the lower number of COVID -19 cases, VE could
not be stratified by time since the doses were administered. Overall, VE appeared similar or
higher in children compared to adults, consistent with findings from the 2023– 24 season.
Between March 2022 and May 2023, maternal COVID -19 vaccination was shown to be effective
in protecting infants under 6 months of age from COVID –19–associated hospitalization, based
on data from the Overcoming COVID -19 Network. Infants in this age group are  not eligible for
vaccination and are at higher risk of severe disease. VE was 54% during the first two months of
life and 35% during the first five months. Effectiveness declined with time since maternal
vaccination, consistent with patterns seen in older  children and adults.
9
 Among pregnant women aged 18– 45 years in VISION, COVID -19 VE against ED and UC visits
was highest when the dose was received during pregnancy, providing 52% protection. A dose
received <6 months before pregnancy provided 28% protection, while a dose given ≥6 months
before pregnancy was not statistically different from zero. These data, collected during 2022
and 2023 when Omicron was the dominant variant, reflect the pattern seen in non- pregnant
adults and children, where more recent vaccination offers the greatest protection.
For the 2023– 24 monovalent COVID -19 vaccines, VE in pregnant women (median 77 days
post-vaccination) was similar to VE in non -pregnant women aged 18– 45 years (median 83 days
post-vaccination) in VISION. Due to limited statistical power, VE by time since dose could not be
assessed.
During the 2024– 25 season, COVID -19 VE against ED and UC encounters among adults aged
≥18 years was 34% overall for the 7– 179 days following vaccination in VISION. VE was 36% for
7–59 days, 35% for 60– 119 days, and 28% for 120– 179 days post -vaccination. VE  was similar
between adults aged 18 –64 years and those aged ≥65 years. Among individuals in the
reference group who did not receive a 2024– 25 COVID -19 vaccine, the median time since their
last dose was approximately 1,000 days.
COVID -19 VE against hospitalization among adults aged ≥65 years without documented
immunocompromising conditions was similar in both the VISION and IVY networks. During the
7–179 days after vaccination, VE was 44% in VISION and 46% in IVY. VE started at 46 % in
VISION and 42% in IVY, declining to 32% and 40% respectively, during the 120- 179 days post -
vaccination. Wider confidence intervals for later periods reflect smaller numbers of vaccinated
cases and controls 4– 6 months before their encounter.
Among adults aged ≥65 years, COVID -19 VE against critical illness remained relatively stable
over time in both the VISION and IVY networks. In VISION, critical illness was defined as ICU
admission or in- hospital death. VE remained consistent even 120– 179 days after vaccination,
suggesting durable protection against severe outcomes. In IVY, VE during the 7– 179 days post -
vaccination was assessed for three escalating outcomes: acute respiratory failure, ICU
admission or death, and invasive mechanical ventilati on or death. VE was highest for the most
severe outcome, with 70% protection against invasive mechanical ventilation or death.
Among adults aged ≥65 years with immunocompromising conditions, COVID -19 VE against
hospitalization during the 2024– 25 season was 38% in VISION and 36% in IVY. Although IVY
did not have sufficient statistical power to estimate VE by time since dose, VISION  appear to
show a trend of increasing VE over time. This pattern has been observed previously and is likely
due to faster waning of infection- induced immunity in immunocompromised individuals, making
the reference group less protected over time. VE in this  group was similar to that in non -
immunocompromised adults, indicating the vaccine is providing meaningful protection.
A sub -analysis from the IVY Network assessed COVID -19 VE against hospitalization by viral
lineage, using whole genome sequencing to confirm KP.3.1.1 and XEC lineages. VE was calculated separately for each lineage, with controls defined as patients with COV ID-like illness
who tested negative for SARS -CoV-2, influenza, and RSV. VE was similar across lineages, with
overlapping confidence intervals. Point estimates were 45% for KP.3.1.1 (median 56 days since
vaccination) and 34% for XEC (median 87 days), with t he difference likely due to time since
vaccination.
Dr. MacNeil concluded that, for both the 2023– 24 and 2024– 25 seasons, in- season COVID -19
vaccination provided additional protection compared to no in- season dose. This included
protection against COVID -19–associated ED and UC visits among children and adul ts,
hospitalizations among adults aged ≥65 years with and without immunocompromising
10
 conditions, and critical illness in older adults. Protection was generally similar across age groups
and appeared to be higher and more durable for more severe outcomes.
VE should be interpreted as the added benefit of the 2023– 24 or 2024– 25 COVID -19
vaccination in a population with high levels of infection- induced, vaccine- induced immunity, or
both. Prior SARS -CoV-2 infection contributes to protection against future illness, but this
protection, like that from vaccination, wanes over time. Increased SARS -CoV-2 circulation in
late summer 2024, just before the approval of the 2024– 25 vaccines, may have raised
population- level immunity against JN.1 lineage strains, potentiall y contributing to lower VE
estimates during the season.
Dr. Kulldorff asked about vaccine efficacy results from randomized, double- blind, placebo-
controlled trials, which are considered the gold standard in medical research. He noted his appreciation for the focus on hospitalizations and deaths, emphasizing tha t these are the most
important outcomes when evaluating COVID -19 vaccines.
Dr. MacNeil responded that many of the randomized controlled trials were conducted in largely
SARS- CoV-2 naïve populations, whereas the current context involves individuals with multiple
exposures to vaccines, prior infection, or both. As a result, clinical trial data are not directly
comparable to present -day vaccine effectiveness estimates. Instead, current efforts focus on
monitoring the real -world impact of COVID -19 vaccines. Across age groups, the added benefit
of recent vaccination has generally ranged from 30% to 50%, reflecting the value of continued
vaccination in populations with existing immunity.
Dr. Kulldorff responded by emphasizing the importance of having a control group that
represents the general population in observational studies. He noted that this is best achieved
through cohort studies. In case- control studies, controls should ideally be drawn from the
general population. He expressed concern about the test -negative design, where controls are
individuals with non- COVID respiratory illnesses, which may represent a distinct population with
different vaccination behaviors. He asked whether m ost of the presented results were based on
the test -negative design or if any were derived from cohort studies or traditional case- control
designs.
Dr. MacNeil acknowledged that case- control studies have limitations compared to traditional
cohort studies. He explained that all platforms used for the presented data rely on case -control
designs, with most using a test -negative design. This approach allows for efficient data
collection in large populations without being cost -prohibitive. He noted that with sufficient
sample sizes, these designs can produce relatively accurate estimates of VE.
Dr. Meissner raised a concern about the definition of COVID -19–associated hospitalizations
used in the data. He noted that many slides referenced hospitalization rates based on a positive RT-PCR test for SARS -CoV-2 but emphasized that this does not necessarily mean the patient
was hospitalized due to COVID -19. He pointed out that being hospitalized with COVID -19 is
different from being hospitalized for COVID -19. Citing a study previously conducted by the
Commonwealth of Massachusetts, he mentioned that less  than half of patients with a positive
test were being treated for COVID -19, suggesting that the presented hospitalization numbers
may overestimate the burden of severe COVID -19 illness.
Dr. Taylor explained that COVID -NET comprises two components: population- based
hospitalization rates based on laboratory -confirmed SARS -CoV-2 positive tests, and clinical
data from a filtered sample of hospitalizations. While the rates include all lab- confirmed cases
regardless of the reason for admission, the clinical data focus only on hospitalizations where
COVID -19 was identified as the likely cause. He noted that this distinction is reflected in the
footnotes on the slide. Dr. Taylor also referenced a peer -reviewed study published in Influenza
11
 and Other Respiratory Viruses , which found that during the 2022– 2023 period, 86 percent of
adult hospitalizations with lab- confirmed COVID -19 were attributable to the virus. Attribution was
based on factors such as illness related to COVID -19 at admission, treatment during
hospitalization, or discharge diagnoses indicating conditions like pneumonia or ARDS.
Dr. Meissner responded by noting that the severity of COVID -19 has decreased since the 2022–
23 period. He acknowledged that hospitalization rates are now much lower. He suggested that
this could be due to viral mutations leading to less severe illness, inc reased population- level
immunity from vaccination or prior infection, or a combination of both. He also raised a similar
concern regarding COVID -19–associated deaths, questioning how many occurred in individuals
with symptoms consistent with a viral infect ion versus those who were classified as COVID -19
cases solely due to a positive test upon hospital admission, as some hospitals require routine
testing for all admitted patients.
Dr. Taylor responded that this is an important question and shared that an analysis is currently
underway to examine deaths using the most recent years of death certificate data. The team is
in the mid- stages of this work and plans to present its findings to ACIP once they are available.
He also noted that, early in the pandemic, all hospital admissions were routinely screened for
COVID -19; however, this is no longer standard practice in most hospitals. Preliminary data from
the 2021– 22 and 2022– 23 seasons suggest that the proportion of hospitalizations attributable to
COVID -19 has slightly increased over time. This is likely due to reduced screening, meaning
that those now tested for COVID -19 are more likely to have symptoms consistent with COVID -
19 illness , rather than being asymptomatic.
Dr. Meissner noted that, based on the most recent CDC data, hospitalization rates for children
aged 0– 4 years are less than one per 100,000. For children under six months, the rate is
approximately 1.6 per 100,000. He asked if this was an accurate interpre tation and emphasized
that, in his view, COVID -19 is currently a very rare cause of hospitalization in both young
children and adults.
Dr. MacNeil responded by emphasizing the importance of considering overall cumulative
numbers, noting that COVID -19 continues to pose a substantial burden, particularly among the
youngest and oldest age groups. He added that comparisons to influenza, as shown in the
earlier slides, highlight that COVID -19 still presents areas for concern.
Dr. Meissner questioned whether Dr. MacNeil felt the rates were accurate.
Dr. MacNeil emphasized that COVID -NET has been a robust platform, capturing data from
approximately 10% of the U.S. population and allowing for strong characterization of illness. He
noted that while modeled national estimates based on this data come with some uncertainty, the
confidence intervals are reasonable, and the resulting burden estimates fall within a reliable and
consistent range.
Dr. Meissner commented on the reference to influenza, noting that while early comparisons between COVID -19 and influenza were common, including himself, it has become clear that the
two viruses behave quite differently. He explained that orthomyxoviruses, like influenza, differ
from coronaviruses in how they mutate and spread. He referred to the concepts of antigenic
shift and drift, suggesting that continued comparisons may not be appropriate, as the viruses
are fundamentally different.
Dr. MacNeil acknowledged Dr. Meissner’s point, clarifying that the intent was not to suggest that
the pathophysiology of influenza and COVID -19 are the same, but rather to compare the overall
population burden. He agreed that it's a valid distinction. He added that it may also be
appropriate to consider using different terminology for COVID -19, rather than borrowing terms
like "drift" and "shift" from influenza. He explained that the key point is the observation of large,
12
 sudden changes in circulating COVID -19 variants that allow the virus to evade pre -existing
immunity. He noted that it may be worth further discussion with influenza experts about adopting
more accurate terms for these rapid changes in dominant COVID -19 var iants.
Dr. Levi questioned the test -negative design, noting that it compares the proportion of
vaccinated individuals among SARS -CoV-2–positive patients with those who test negative. He
proposed that a lower vaccination rate in the positive group might still be c onsistent with
vaccines increasing overall susceptibility to multiple respiratory viruses, with vaccinated people appearing in both groups but slightly less often among the positives. Such a scenario, he
argued, could create the appearance of vaccine effec tiveness even if vaccination provides no
benefit or increases vulnerability. He added that some of the data presented suggest this may be occurring, as the rate of hospitalization among people with updated vaccination appears
higher than their relative proportion in the general population. He stated this should raise
concern and prompt further consideration of alternative explanations beyond vaccine efficacy.
Dr. Link -Gelles explained that the goal of the TND is to use controls that represent the
vaccination coverage in the population from which the cases originated. A key strength of TND
is that controls have the same symptoms as the cases and seek care and testing at the same
facilities, making them population- based in this context. She emphasized that while the controls
are not representative of the general population, they are representative of individuals who
would have been hospitalized if they had COVID -19. In this analysis, controls are often older
adults hospitalized with acute respiratory illness, so their vaccination coverage would not be expected to match that of the broader, generally healthier U.S. population. Due to this design,
the controls are considered suitable for estimating the relative impact of vaccination.
Dr. Hoeg expressed concerns about the potential for confounding in the test -negative design,
echoing the points raised by Dr. Kulldorff and Dr. Levi. She questioned why patients who test positive for influenza and, in people aged ≥60 years, RSV, are excluded if the goal is to
compare groups with similar symptoms, with one group testing positive for COVID -19 and the
other not. She noted that these groups may differ in meaningful ways, making it difficult to ensure they are truly comparable. Dr. Hoeg emphasiz ed the importance of randomized
controlled trials in minimizing bias and avoiding uncertainty about whether observational data
accurately reflects VE.
Dr. Link -Gelles responded that including individuals who test positive for another vaccine-
preventable disease as controls or cases could introduce bias into the study. She explained that
vaccine status is correlated across diseases, and individuals who test positive for influenza or
RSV are often less likely to have received those vaccines, which also makes them less likely to
have received the COVID -19 vaccine. This correlation can distort the results. She cited
published literature supporting this concer n and explained that, for this reason, controls who test
positive for influenza or RSV are excluded. She also noted that the study teams work closely
with sites to ensure that cases and controls have similar symptoms, and they have analyzed
and published data confirming that symptom profiles and severity are balanced between groups.
Dr. MacNeil added that while randomized clinical trials are valuable, there are real -world
limitations related to time and cost. He emphasized that the test -negative design provides a
robust and efficient method for generating real -world vaccine effectiveness data promptly. For
example, reviewing VE data from the most recent season in June would not be feasible using
randomized trials due to the time required for enrollment, follow -up, and analysis. He noted that
for the CDC, the test -negative design is a p ractical and effective approach to assess the real -
world impact rapidly.
Dr. Levi commented on the genomic evolution of SARS -CoV-2 variants, noting that while there
is continuous evolution, two major jumps stand out. He raised two questions related to this
13
 observation. First, he asked whether any analysis has been done to compare this pattern to
other viruses, such as influenza, to determine how common such large evolutionary jumps are.
Second, he inquired about the evolutionary pressures that might be drivi ng these shifts, as such
changes typically result from natural selection. He also questioned whether there has been any
analysis of a possible connection between vaccination policies and the observed evolution of
the variants, noting that the pattern appears striking.
Dr. MacNeil responded that the evolution of COVID -19 has indeed been full of surprises, with
the emergence of major variants, such as Omicron, representing sudden and significant changes. He noted that these large shifts likely reflect a combination of sel ective pressures
within the human population, such as pre- existing immunity, as well as unique characteristics of
the virus itself. He emphasized that the situation is complex and dynamic. Dr. MacNeil also
emphasized the importance of ongoing genomic surveillance and real -time sequencing, which
enable experts to detect and monitor variant changes as they emerge. He emphasized the
importance of maintaining this capacity to respond quickly to any unexpected shifts in the virus.
Dr. Meissner added to the discussion by noting the increasing complexity of SARS -CoV-2
evolution, particularly the emergence of convergent evolution, where different strains develop
the same mutations in specific regions of the spike protein. He emphasized that this makes the
situation even more challenging to analyze. Shifting to the topic of study design, Dr. Meissner
acknowledged that the case- control approach, including the test -negative design, is not perfect
and carries certain limitations, such as a potential bias toward individuals who are more likely to seek medical care. However, he pointed out that it remains the most practical option for
evaluating vaccine effectiveness within a limited timeframe, as is done with influenza vaccines,
which are updated annually. He concluded that, despite its flaws, the case- control design is a
well-established method for evaluating vaccines.
Dr. Kulldorff emphasized the importance of distinguishing between traditional case- control
studies and the test -negative design. He noted that, methodologically, these are very different
approaches and that the quality of the information they produce can v ary significantly.
Dr. Taylor clarified a question regarding the COVID -NET hospitalization rates presented earlier
by Dr. MacNeil. He explained that the figures shown on the slides represent cumulative rates,
which are the sum of weekly hospitalization rates over a period fr om July 2024 through May
2025. For children <6 months, the cumulative hospitalization rate was 268 per 100,000,
comparable to the rate among adults aged 65 to 74 years. For children aged 6 to 23 months,
the cumulative rate was 100 per 100,000, similar to t he rate for adults aged 50 to 64 years,
which was 103 per 100,000. Dr. Taylor emphasized that while weekly rates may seem small,
the cumulative rates provide a more accurate picture of disease burden over time.
Dr. Levi asked whether the proportions of COVID -19–associated hospitalizations by age group
differ from overall hospitalization patterns for all causes. Specifically, he questioned whether the
distribution seen here deviates from general hospitalization tr ends across age groups or if it is
consistent with typical patterns.
Dr. Taylor responded that COVID -NET, as one of the RESP -NET platforms, is specifically
designed to collect data on SARS -CoV-2–positive, COVID -19–associated hospitalizations. As
such, it does not include data on all -cause hospitalizations and cannot be used to directly
compare COVID -19 hospitalization rates to general hospitalization rates across age groups. He
noted that while previous ACIP meetings have included analyses comparing underlying conditions among adults hospitalized with COVID -19 to those in the general population, COVID -
NET data do not support comparisons between COVID -specific and general hospitalization
patterns.
14
 Dr. Sarah Meyer (CDC/NCEZID) shared an update on how the CDC monitors vaccine safety.
The CDC and interagency partners launched a comprehensive vaccine safety monitoring
program for COVID -19 vaccines. A wide range of potential safety outcomes has been rigo rously
assessed through complementary passive and active surveillance systems. Myocarditis has
been causally linked to mRNA COVID -19 vaccines. Common adverse events, such as local and
systemic reactions and allergic responses, have also been observed. The CDC continues to
actively monitor the safety of COVID -19 vaccines.
Vaccine safety monitoring is essential throughout the vaccine life cycle, from early research and
clinical trials to regulatory review. After a vaccine is authorized or approved, the CDC begins
safety monitoring in coordination with the FDA, the Indian Health Service, the Department of
Defense, and the Department of Veterans Affairs.
The CDC employs a robust, complementary system of layered safety monitoring to promptly
identify and evaluate potential concerns, enabling public health officials and policymakers to
take timely action. Most systems have been in place for decades, but the CDC continues to
improve existing systems and develop new ones to fill gaps, such as v -safe, which was
launched to monitor the safety of COVID -19 vaccines.
The Vaccine Adverse Event Reporting System (VAERS) is the nation's early warning system for
vaccine safety, co -managed by the CDC and the FDA. It relies on spontaneous reports from
across the country to detect potential safety signals, including rare event s. Healthcare providers
and manufacturers are required by the National Childhood Vaccine Injury Act to report certain
adverse events; however, patients or their family members can also submit reports. It's essential
to note that reporting an event to VAERS  does not necessarily mean that the vaccine caused it.
VAERS is used for signal detection and hypothesis generation, not to determine causality.
The Vaccine Safety Datalink (VSD) is a collaborative system that generates high- quality data on
vaccine safety. It includes 13 integrated healthcare organizations and serves approximately
15.5 million people annually. VSD uses active surveillance through electronic medical records
and chart reviews, enabling rapid monitoring of both prespecified and unexpected events.
Unlike VAERS, which is primarily used for signal detection, VSD can detect and assess safety
signals. The network is also known for its strong expertise, which has led to the development of
innovative methods for monitoring vaccine safety.
The Clinical Immunization Safety Assessment (CISA) Project is a network that supports vaccine
safety from the individual to the population level. It includes eight medical research centers with
vaccine safety experts and specialists. CISA provides clinical  consultations on complex
immunization issues to support patient care and research real -world vaccine safety questions
not addressed in pre -licensure trials. CISA consultants also help inform the CDC’s public health
guidance on clinical immunization safety  issues.
V-safe After Vaccination Health Checker is the CDC’s newest tool for direct -to-consumer
vaccine safety monitoring. It is a smartphone and web- based, self -reported active monitoring
system established during the COVID -19 pandemic. v -safe can provide early i nformation on
reactogenicity and other health events, especially for new vaccines and populations not
included in clinical trials. For example, it helped enroll over 23,000 pregnant women into a
voluntary registry to monitor maternal and neonatal outcomes after COVID -19 vaccination. V -
safe is flexible, quickly deployable, and plays a key role in emergency preparedness and response. It is also integrated with VAERS to streamline reporting serious adverse events.
These systems support the CDC’s comprehensive approach to COVID -19 vaccine safety, which
includes surveillance of reported events, epidemiologic studies, clinical research, and a pregnancy registry. The approach also utilizes rapid cycle analysis, data mining of over 60,000
15
 outcomes, and patient surveys to identify and assess potential safety concerns and health
impacts following vaccination.
An overview of the extensive body of evidence on COVID -19 vaccine safety was provided.
Since the rollout in December 2020, data have been documented in 17 Vaccine Safety
Technical Work Group reports, 28 presentations to federal advisory committees, 29 publ ications
in the MMWR, 114 peer -reviewed manuscripts, and through nearly 10 million participants
enrolled in v -safe. This information was collected during the largest vaccination effort in U.S.
history, with approximately 1 billion doses distributed.
Dr. Meyer recapped that three types of COVID -19 vaccines were authorized or approved for use
in the United States: mRNA vaccines by Pfizer -BioNTech and Moderna, a protein- based
vaccine by Novavax, and a viral vector -based vaccine by Janssen. The use of the  Janssen
vaccine became limited in April 2021 after the VAERS system detected six reports of thrombosis with thrombocytopenia syndrome (TTS). In response, the FDA and the CDC issued
a 10- day pause in its use. By December 2021, ACIP issued a preferential recommendation for
mRNA vaccines, and in June 2023, the EUA for Janssen was revoked. The vaccine is no longer in use in the United States. This situation highlighted how federal safety systems worked
together to identify and address a concern regarding vacci ne safety promptly.
Dr. Meyer noted that post -authorization safety data for Novavax remain limited due to its later
authorization in July 2022 and low uptake in the U.S. Therefore, the remainder of the discussion
focused on the safety of mRNA COVID -19 vaccines, which are supported by a large and
growing body of evidence.
The CDC has evaluated at least 65 specific outcomes to assess the safety of the COVID -19
vaccine using a variety of systems and epidemiologic methods. Since December 2020, weekly
rapid cycle analyses (RCAs) in the Vaccine Safety Datalink have tracked up to  23 prespecified
outcomes in over 12 million people, based on clinical trial data, known vaccine risks, and
biological plausibility.
Automated statistical testing compares rates of outcomes in post -vaccination risk intervals with
those in comparison periods. When a signal is detected, further analysis or chart review is
conducted. The system is designed to be sensitive, and not all signals indicate a true safety
concern.
Between 2020 and 2025, eight statistical signals were identified through VSD’s weekly rapid
cycle analyses. These included acute myocardial infarction, venous thromboembolism, immune
thrombocytopenic purpura, ischemic stroke, seizure, Guillain- Barré syndro me, Bell’s palsy, and
myocarditis.
When a signal is detected, the CDC conducts further investigations to determine if it reflects a true safety concern or a false positive. These follow -up steps include chart reviews, trend and
cluster analyses, additional studies such as self -controlled case series, and a review of data
from other monitoring systems, including VAERS and partner databases managed by the FDA
and VA.
After completing these investigations, the CDC determined that there is an increased risk of
myocarditis following mRNA COVID- 19 vaccination. No clear or consistent evidence of a safety
concern was found for the other outcomes mentioned.
Using data from the Vaccine Safety Datalink, the CDC assessed the incidence of myocarditis
within seven days of COVID -19 vaccination among individuals aged 12– 39 years, by season
and dose. Rates were highest in males, peaking among those aged 16– 17 years. Myocarditis
was rare in children <12 years and in adults >50 years. The risk was highest after the second
16
 dose in the primary series but remained elevated after the first monovalent booster. In later
seasons, incidence declined and approached the background rate of <2 cases per million.
Similar patterns have been observed in VAERS reports. Several factors may explain the decline
in myocarditis rates in recent years, including increased overall population immunity, a longer
interval between doses, and fewer people receiving more than one dose per year.
The FDA recently shared updated data on myocarditis and pericarditis following mRNA COVID -
19 vaccination from the Biologics Effectiveness and Safety (BEST) system during the 2023–
2024 season. In April, the FDA issued safety labeling change notification let ters to vaccine
manufacturers, instructing them to include new information on myocarditis and pericarditis. FDA
approved safety labeling updates for Comirnaty and Spikevax to reflect this new safety
information.
CDC follow- up studies show that most adolescents and young adults have recovered from
myocarditis after receiving an mRNA COVID -19 vaccine. These studies included individuals
aged 12– 29 years with a VAERS report filed between January and November 2021, along with
input from their healthcare providers. Based on assessments by cardiologists or other providers, 83% were considered fully or probably recovered within 90 days of symptom onset, and by one
year, at least 90% had recovered.
Most individuals showed improvement in symptoms, as well as in cardiac imaging and testing
results. A subset who underwent cardiac MRI one year after onset most commonly showed late
gadolinium enhancement, which may suggest the presence of fibrosis. However, the clinical
significance of this finding is unclear, as most were considered recovered and had been cleared
for all activity. There were no known deaths or cardiac transplants in this group.
COVID -19 vaccine safety data for children aged 6 months to 11 years show a low risk of
myocarditis, particularly in those under 5 years. No statistical signals for myocarditis have been
detected in the Vaccine Safety Datalink, and no confirmed cases have been reported in VAERS
or the VSD for children under 5. VSD rapid cycle analyses also found no increased risk for 22
other prespecified outcomes. Most cases of MIS -C after vaccination had evidence of prior
SARS- CoV-2 infection.
The majority of COVID -19 vaccine reports submitted to VAERS for children <12 years were
related to vaccine administration errors. From October 2021 to April 2025, approximately 74% of
reports for children aged 6 months to 4 years and 70% for those aged 5 t o 11 years involved
errors, such as expired product, incorrect dose or formulation, administration to the wrong age
group, or preparation issues. Few of these reports included an actual adverse event. The high
number of administration error reports likely reflects the complexity of the pediatric COVID -19
vaccination program, particularly early in the rollout when dosing, recommendations, and
storage requirements varied by product. CDC is expanding its efforts to prevent vaccine
administration errors in coll aboration with the FDA.
CDC has actively assessed the safety of COVID -19 vaccines in pregnant women through
multiple efforts. A voluntary pregnancy registry enrolled over 23,000 pregnant participants to
monitor outcomes. Additionally, the CDC has conducted seven observational studies using
survey and medical record data. In the Vaccine Safety Datalink, over 45,000 pregnant women
have been evaluated through 11 cohort, case- control, and surveillance studies to date.
Across these CDC studies, the evidence shows no increased risk of adverse maternal outcomes associated with COVID -19 vaccination, including 25 medically attended adverse
events, serious acute events, pregnancy -related conditions, or maternal ICU admissions .
Vaccination was also not associated with adverse pregnancy outcomes such as miscarriage,
17
 stillbirth, preterm birth, or small for gestational age. Additionally, no association was found
between maternal vaccination and major birth defects, neonatal ICU admission, or infant death.
The CDC has conducted studies to address public concerns about the safety of the COVID -19
vaccine. In response to reports of abnormal uterine bleeding, analyses using VAERS, VSD, and
v-safe found no association between vaccine availability and the incidenc e of medically
attended abnormal uterine or postmenopausal bleeding. The vaccine was also not linked to
increased bleeding severity. CDC also assessed reports of tinnitus using data from VAERS and
VSD. No safety signals were detected, and findings did not support an increased risk of tinnitus
following COVID- 19 vaccination.
CDC monitors death reports following mRNA COVID -19 vaccination through VAERS. As of May
30, 2025, 19,417 domestic deaths had been reported after vaccination. Under FDA emergency
use authorizations and CDC provider agreements, healthcare providers were required to report
all deaths occurring within 30 days after COVID -19 vaccination, regardless of cause or
circumstances. This requirement does not apply to other vaccines.
VAERS is not designed to assess causality. CDC evaluated deaths reported following mRNA
COVID -19 vaccination through January 31, 2023. During this period, the CDC received 17,631
domestic VAERS reports of death following COVID -19 vaccination. After clinical review, 52 were
excluded as they did not represent actual deaths, 1,790 involved non -mRNA vaccines, and
2,940 lacked a confirmed cause of death.
This left 12,849 reports with confirmed causes of death, identified through autopsy, death
certificate, medical records, or the VAERS report. Among these, 78% were aged ≥65 years,
15% were 50– 64, 6% were 18– 49, and 5% were <18 years.
CDC assessed all reported deaths in the general U.S. population during this period using death
certificate data from the National Center for Health Statistics' multiple cause of death database,
categorized by ICD -10 codes. Observed- to-expected ratio analys es were conducted for each
age group by comparing the number of cause -specific deaths reported to VAERS within 42 days
of mRNA COVID- 19 vaccination to the number of expected deaths in the general U.S.
population.
CDC found that reported death rates after mRNA COVID -19 vaccination were below
background rates in the general U.S. population. The most common causes of death reported to
VAERS, such as heart disease, COVID -19, cerebrovascular disease, and general signs and
symptoms like shock, were consistent with the leading causes of death nationally. In children, congenital malformations were also reported, and among adults aged ≥18 years, malignant
neoplasms were included.
Across all age groups, the observed -to-expected death ratio was <1, indicating fewer reported
deaths than expected within 42 days of vaccination. Despite the limitations of VAERS, these
findings suggest no association between mRNA COVID -19 vaccination and increased mortality.
In addition to reviewing VAERS reports, the CDC conducted two self -controlled case series
evaluations using the Vaccine Safety Datalink, one in the general population aged 12 years and older and one in Medicare beneficiaries aged 65 years and older. Pfizer  and Moderna vaccines
were analyzed separately. Both studies found no increased risk of non -COVID -19 mortality, all -
cause mortality, cardiac -related mortality, or non- COVID -19 cardiac -related mortality within 28
days following vaccination. Relative incidence rates were significantly <1 in all cases.
These findings are consistent with results from a separate cohort analysis in the VSD. The
robust methods used across these analyses provide strong evidence of no increased risk of
death after mRNA COVID -19 vaccination and suggest a potential protective ef fect.
18
 CDC uses data mining in the Vaccine Safety Datalink to detect unexpected adverse events
following COVID- 19 vaccination. This approach evaluates over 60,000 possible outcomes within
70 days of vaccination using tree -based analysis of ICD -10 codes. Assessments have been
conducted for the primary series, initial booster, and bivalent booster. No new safety concerns
have been identified beyond known events such as myocarditis, pericarditis, allergic reactions,
and common local or systemic reactions.
Dr. Meyer summarized that several adverse events have been identified following mRNA
COVID -19 vaccination. Most, such as local and systemic reactions, acute allergic reactions,
syncope, and shoulder injuries, are common to many vaccines. Myocarditis and pe ricarditis
have also been observed specifically following COVID -19 vaccination. These conclusions are
based on the evaluation of at least 65 specific safety outcomes, data mining of over 60,000
potential outcomes, investigation of multiple statistical signals, and numerous epidemiologic
studies.
These findings align with the National Academies of Sciences, Engineering, and Medicine's
consensus report on the adverse effects of COVID -19 vaccines, commissioned by HRSA and
published in 2024. The report reviewed over 400 studies on vaccine safety. It c oncluded that
there is evidence supporting a causal association between mRNA COVID -19 vaccines and
myocarditis. It also found that the evidence favors rejecting a causal link between vaccination
and six other outcomes: Guillain- Barré syndrome, Bell’s palsy , TTS, myocardial infarction,
ischemic stroke, and female infertility. For 13 other outcomes, the evidence was deemed inadequate to accept or reject a causal relationship.
COVID -19 vaccines have been evaluated under the most extensive vaccine safety monitoring
program in U.S. history. This surveillance quickly identified and characterized the risk of myocarditis following mRNA vaccination. No other confirmed safety concerns have been
identified beyond those commonly seen with other vaccines, such as local reactions, systemic
symptoms, or allergic responses. CDC continues to prioritize COVID -19 vaccine safety, with at
least 30 ongoing studies or monitoring activities.
Dr. Hibbeln stated that he has long been interested in risk -benefit evaluations and asked
whether a broad summary of the data presented would be accurate. He noted that the evidence
suggests a minimal to no risk of death from receiving a COVID -19 vaccine, whereas Dr.
MacNeil’s presentation indicated a substantial risk associated with not being vaccinated. He
asked whether it would be reasonable to describe the benefit of vaccination as a 40-  to 50 -
percent reduction in risk, with essentially zero risk of death from the vaccine. He framed this as
a general assessment of the overall risk -benefit balance.
Dr. Meyer responded that several studies have been conducted to evaluate the risk of mortality
following COVID- 19 vaccination, and no increased risk has been observed. In VAERS analyses
comparing observed to expected deaths, the data did not show a higher -than-expected number
of deaths. Similarly, evaluations using the Vaccine Safety Datalink found no increased risk of
mortality after vaccination. From a safety perspective, the data support confidence that COVID -
19 vaccines are not associated with an increased risk of death. Regarding the overall risk -
benefit assessment, Dr. Meyer noted interest in hearing the committee’s evaluation of those
factors.
Dr. MacNeil added a rough estimate to illustrate the potential impact of vaccination on COVID -
19 mortality. Using a hypothetical scenario, if there were about 40,000 COVID -19-related deaths
in a year and none of those individuals had been vaccinated, then applying the observed
vaccine effectiveness, approximately half, or about 20,000, of those deaths might have been
prevented. This was presented as a general approximation to highlight the potential benefit of
vaccination in reducing deaths.
19
 Dr. Malone asked for clarification on the safety monitoring timeframes presented. Specifically,
the question focused on whether the post -vaccination periods, defined as either 28 days or 42
days, apply to individuals who have completed at least two doses. Dr. Malone requested
clarification on how "post -vaccination" is defined in the context of the data that was shared.
Dr. Meyer responded that the analyses included individuals who had received at least one dose
of a COVID -19 vaccine. For the VSD analyses, three separate evaluations were conducted: one
after completion of the primary series, one following the original booster, and one after receiving
the Omicron booster.
Dr. Malone followed up by asking whether the analysis of adverse event associations, like the
mortality analysis, was also limited to a 28- day post -vaccination window.
Dr. Weintraub explained that analyses for the Vaccine Safety Datalink were set up to examine
21-day and 42- day risk intervals following doses one and two of the primary series. This
approach has been consistently applied with each new vaccine recommendation, including the
most recent season. The 42- day window also allows for scanning of shorter time intervals within
that period to identify potential clusters of increased risk, using Martin Kulldorff’s clustering method. It is standard practice to use a 42 -day risk interval and to compare it to a historical
control period, typically days 43 to 84 after vaccination.
Dr. Malone commented on the presentation of the adverse events assessed, noting that the slide listing the 65 outcomes was difficult to interpret. He suggested that it would be helpful if the
information were structured more clearly, such as in alphabetical order, to better understand the
full range of events evaluated. Based on his review, he inferred that hypertension, tachycardia,
and POTS were included in the analyses and were not found to be associated with COVID -19
vaccination.
Dr. Meyer responded by explaining that both VAERS and the Vaccine Safety Datalink (VSD) use prespecified lists of outcomes to monitor and flag for further review. In addition to tracking
prespecified outcomes, VSD also investigates other emerging concerns as needed.
Dr. Meyer acknowledged that the slide listing the 65 outcomes was intended to provide a brief
overview and could be made clearer. A more detailed list can be shared if needed. She also
noted that data mining is used to detect unexpected outcomes without specifying them in
advance. None of the conditions mentioned, including POTS, appeared as signals in the data
mining. While some studies on outcomes, such as POTS, have been referenced in the National
Academies report, the available data are limited. Based on the CDC’s comprehensive approach,
including both targeted analysis and broad surveillance, the primary safety concerns identified
remain myocarditis and common vaccine- related reactions.
Dr. Malone emphasized the public’s need for transparency and recommended that a clear,
comprehensive list of all safety outcomes and analyses be made publicly available. He also
asked whether potential lot -to-lot variability in vaccine manufacturing had been examined,
noting that such variability could mask clusters of adverse events when data are viewed in
aggregate, and requested details on how this issue has been addressed.
Dr. Meyer responded that the CDC works closely with interagency partners on vaccine safety,
with each agency having distinct roles. She noted that lot -specific issues are typically assessed
by the FDA and deferred to FDA colleagues for any additional infor mation on that topic.
Dr. Meissner emphasized that physicians are trained to report any adverse event (AE) after
vaccination to VAERS, regardless of causality. Given the high volume of vaccinations, many
reported AEs are unrelated to the vaccine. He clarified that VAERS is not used to determine
incidence rates but to detect safety signals, which are then evaluated further using systems like
20
 VSD. He noted most VAERS reports do not indicate a causal relationship. Dr. Meissner then
asked Dr. Meyer about the long- term follow- up of myocarditis cases, particularly regarding
individuals with late gadolinium enhancement on cardiac MRI, which may suggest scarring and
potential risk for arrhythmias or sudden death. He also inquired about data from manufacturers
on troponin levels and markers of subclinical myocarditis, which he understood had been
requested but had not yet been reported.
Dr. Meyer responded that some studies have evaluated subclinical myocarditis, including those
that measure biomarkers such as troponin in asymptomatic individuals. These studies have not
shown adverse clinical outcomes in those cases. However, the long -term significance remains
uncertain and requires ongoing monitoring. CDC is closely tracking this issue, and FDA is conducting similar studies with comparable findings. This information is expected to be included
in upcoming safety labeling updates, and both the CDC and the FDA plan to continue long -term
monitoring.
Dr. Levi questioned whether traditional vaccine safety surveillance methods, which focus on
short -term adverse events, are sufficient for COVID -19 vaccines, given evidence that residual
mRNA and spike protein may persist in the body for months. He suggeste d this could reduce
the sensitivity of current approaches and called for broader methods. He cited a VA study
showing higher adverse events with Pfizer compared to Moderna. He emphasized the
importance of accounting for factors like the healthy vaccinee ef fect when comparing mortality
rates. He asked whether surveillance systems are adapting to address the unique characteristics of COVID -19 vaccines.
Dr. Meyer responded that the United States has one of the strongest vaccine safety systems in the world and expressed confidence in its current approach. However, efforts are ongoing to identify ways to improve the system, especially in monitoring long- term outcomes after
vaccination. She noted that detecting long- term effects is challenging because, over time,
confounding factors such as infections or unrelated health events make it more difficult to
separate vaccine- related effects from other causes. Dr. Meyer welcomed input from the
committee on how to enhance long- term safety monitoring.
Dr. Malone followed up by emphasizing that the pharmacokinetics of mRNA vaccines differ significantly from traditional vaccines. He noted that prolonged antigen presence in the body, up
to 700 days according to a Yale study, is unprecedented in vaccinology . This extended
exposure has been linked in animal models to immune system effects such as broad
immunoglobulin class switching, which are not currently captured by existing safety monitoring
systems. Dr. Malone suggested these changes could affect overall  immune function and
influence vulnerability to other infectious diseases. He related this concern to Dr. Levi’s earlier
question about vaccine effectiveness estimates. While acknowledging the rigor of the current
safety framework, he encouraged expanding safety analyses to consider the unique profile of
mRNA vaccines, including the potential for delayed or immune- related effects. He
recommended broadening the scope of monitoring to include potential long- term immunologic
risks and benefits, which could hel p address public concerns and improve understanding of
these products.
Dr. Meyer explained that since vaccination efforts began in December 2020, the CDC has maintained robust monitoring for several years. The current systems are designed to detect any
adverse events, including those that may be cumulative over time or result  from multiple doses.
If there were any emerging safety concerns or effects on organ systems, the existing
surveillance infrastructure would be well -positioned to identify them.
Dr. Thornburg noted that preclinical animal studies have shown spike protein detection up to nine days after injection, but not in the liver, and no detection beyond that time. In humans,
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 limited data from an autopsy study of 20 individuals revealed that vaccine mRNA was detected
only in axillary nodes within 30 days post -vaccination, and not in the spleen or mediastinal
lymph nodes. Protein was not detected in lymph nodes, the left ventric le, liver, or other organs,
with only nonspecific staining observed.
Dr. Georgina Peacock (CDC/NCIRD) presented on COVID -19 vaccine coverage and
implementation. One of the primary data sources used by the Immunization Services Division at CDC to assess vaccine coverage, including COVID -19 vaccination, is the National Immuni zation
Survey (NIS). The NIS is a random -digit-dial cellular telephone survey of U.S. adults aged ≥18
years across all states, 5 local jurisdictions, and U.S. -associated territories. For children, data is
reported by a parent or guardian. All responses are self-reported. The survey collects data from
about 15,000 adults per week or around 60,000 adults per month. The data is weighted to represent the non -institutionalized U.S. population.
From September 2024 through April 2025, COVID -19 vaccination coverage for at least one
dose reached 44% among adults aged 65 years and older and 23% among adults aged 18
years and older.
COVID -19 vaccination coverage among older adults increased between the 2023– 2024 and
2024– 2025 seasons. For adults aged 65– 74, coverage increased by nearly 5 percentage points,
while adults aged 75 years or older saw an increase of about 8 percentage point s by the end of
the 2024– 25 season.
As of April 2025, approximately 5.6% of children under 4 years old were up to date with COVID -
19 vaccination for the 2024– 2025 season. Among children aged 5– 17 years, about 16% had
received at least one dose since August 2024. Overall, 13% of children aged 6 months to 17
years were up to date with their COVID -19 vaccination for the 2024– 2025 season.
Among immunocompromised adults who received their first 2024- 2025 COVID -19 vaccine dose
in August or September 2024, 8% were fully vaccinated with two doses by the end of March
2025. When stratified by age, full -vaccination coverage was 16.6% for adults aged 50– 64, 2.4%
for those aged 18– 49, and 0.8% for adults aged 65 years and older.
Dr. Peacock summarized that COVID -19 vaccination coverage for older adults improved in the
2024– 2025 season compared to the previous year. Coverage among adults aged 18 years and
older remained similar between seasons, and approximately 13% of children aged 6 months to 17 years were up to date with their COVID -19 vaccinations by the end of April 2025.
Dr. Levi asked about vaccine uptake among healthcare professionals, as their vaccination behaviors can influence public trust and recommendations.
Dr. Peacock responded that data on COVID -19 vaccination rates among healthcare
professionals is not included in the specific dataset presented. However, the National Immunization Survey and other sources do collect this information. Dr. Peacock offered to bring
relevant data to a future ACIP meeting or share it with the work group, noting that it is not
currently available for discussion.
Dr. Meissner noted that COVID -19 vaccine uptake remains low, with less than 20% coverage
among young children and even among high- risk adults over 75. He asked whether low public
uptake influences the recommendations made by ACIP, specifically if low vacci nation rates
among children affect whether ACIP continues to recommend the vaccine for that group.
Dr. Peacock responded that this is a discussion for the committee to consider. She noted being
encouraged by the increase in vaccination among adults over 65, especially those over 75. She
suggested that this may reflect healthcare providers recommending t he vaccine to patients with
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 a higher risk of hospitalization or death. She added that the final recommendation ultimately
comes from the committee.
Dr. Meissner expressed concern that if the CDC issues recommendations that the public does
not follow, it could erode confidence in those recommendations. He acknowledged that there
may not be an easy solution but emphasized the importance of considering public acceptance
when developing guidance.
Dr. Kulldorff emphasized that the committee must base its recommendations on evidence -
based medicine. However, he acknowledged that the low COVID -19 vaccination rates among
children likely reflect a lack of trust among many parents in the recommendations i ssued by the
ACIP. He agreed that Dr. Meissner raised an important and timely concern.
Dr. Daskalakis added that part of the evidence- to-recommendation framework used in the work
group includes an assessment of both feasibility and acceptability. He clarified that these factors
have historically been part of all vaccine- related discussions and are built into the process that
informs committee discussions and ultimately leads to recommendations.
Dr. Meissner asked whether there is a defined threshold at which continuing to make a
recommendation may no longer be beneficial, particularly if uptake remains persistently low.
Dr. Daskalakis responded that this is precisely why the committee holds these discussions. As
feasibility, acceptability, and uptake are reviewed within the work group, that information is
brought to the committee for consideration. Based on this feedback,  the committee ultimately
makes recommendations, which can then be further reviewed.
Dr. Pebsworth expressed concern about the low uptake of COVID -19 vaccines and the high
volume of reports submitted to VAERS compared to other vaccines. She noted that, as of her
last review, approximately 1.6 million reports had been submitted, and cited s tudies suggesting
that only about 10% of adverse events are typically reported, raising the possibility of
underreporting. Given these concerns, she emphasized the importance of transparency and
access to data not typically shared, including findings from preclinical animal studies,
reproductive toxicity data, and biodistribution studies. She believes these data could help clarify
current uncertainties.
Dr. Meyer addressed concerns about underreporting in VAERS by clarifying that studies often cited to support underreporting typically include mild events, such as sore arms or rashes, which
are often not reported. She noted that CDC research has shown significantly higher reporting
rates for serious adverse events. For example, VAERS captures up to 76% of anaphylaxis
cases and up to 64% of Guillain- Barré Syndrome cases, depending on the vaccine. She added
that similar findings have been observed for intussusception after rotavirus vaccination and
vaccine -associated polio. Dr. Meyer emphasized that the CDC is confident that a majority of
serious adverse events are reported to VAERS.
Dr. Levi acknowledged improvements in reporting but maintained that underreporting of adverse
events, particularly myocarditis, likely still exists across systems. He emphasized that
comparing rates from VAERS, clinical diagnoses, and studies measuring biomarkers, such as
troponin levels, before and after vaccination, reveals discrepancies. While the underreporting
may not be to the extent of 10%, it remains significant. He also noted that some serious adverse
events appear in VAERS at rates exceeding those seen with other vaccines, even after
adjusting for the number of doses administered, which may indicate a signal that warrants
further investigation.
Dr. Adam MacNeil (CDC/NCIRD) concluded the COVID- 19 session with a partial presentation
on evidence- to-recommendations (EtR). The EtR framework outlines key domains used to guide
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 decision- making, including public health problem, benefits and harms, values, acceptability,
feasibility, resource use, and equity. Each domain is linked to specific guiding questions. The
first two domains, public health problem and benefits and harms, were reviewed and discussed
by the workgroup. The remaining domains and final polling were scheduled for the final
workgroup call.
The work group has consistently reviewed data related to the public health problem and benefits
and harms domains of the EtR framework. Most recently, summaries of these domains were
discussed during the May 29 and June 5 work group calls. These domains are largely informed
by the epidemiology, vaccine effectiveness, and safety data previously presented, and were
reflected in the June 12 ACIP meeting presentations. The work group had planned to review the
remaining EtR domains and complete final polling before the ACIP meeting. However, because the scheduled work group call did not take place, the EtR was not finalized, and final polling was
not conducted.
Dr. MacNeil summarized the work group’s considerations on the public health problem, noting that while the burden from COVID -19 has declined year over year since 2021, substantial illness
and death continue. Hospitalization and death rates remain highest among adults 65 years and older and infants six months and younger. Children under two years have the highest illness
and death rates among pediatric groups, though deaths can occur at any age. Maternal vaccination remains the best protection for pregnant women and infants under six months who
are not eligible for vaccination.
For the benefits and harms domain, the work group concluded that the 2024– 2025 COVID -19
vaccination provides clear benefits in reducing hospitalizations and severe disease, particularly
in adults. The vaccine has demonstrated consistent effectiveness across age groups based on prior formulations. Safety surveillance has identified myocarditis and pericarditis following
mRNA vaccination, but no other serious risks have been confirmed beyond typical vaccine-
related reactions. The work group also recognized that pregnant individuals face higher risks
from COVID -19, and maternal vaccination offers protection to infants under six months, who are
not yet eligible for vaccination.
Dr. Kulldorff thanked the presenters for their informative updates and acknowledged the thoughtful discussion that followed. He noted that no vote was scheduled on the topic and that
the committee looks forward to receiving the working group's report befor e the next meeting. He
expressed appreciation for both the CDC presenters and the many contributors behind the scenes.

AGENCY  UPDATES

The C
enters for Disease Control and Prevention (CDC)
Dr. Demetre Daskalakis from the National Center for Immunization and Respiratory Diseases
(NCIRD) provided an update on current domestic outbreaks. He reported that as of the meeting date, the CDC has identified 1,227 measles cases across 37 U.S. jurisdictions in 2025, with 23 outbreaks accounting for 89% of cases. A significant portion of these cases is linked to a large outbreak in the Southwest, with Texas reporting 750 cases across 35 counties and New Mexico
reporting 81 cases. There are signs that the outbreak is plateauing, with a decline in new cases
in the Southwest. However, the CDC continues to monitor for global introductions of measles into the U.S., though recent cases have resulted mainly in short, self -limiting transmission
chains. The overall  risk to the U.S. population remains low; however, continued vigilance is
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 necessary, particularly in under -immunized populations. Dr. Daskalakis also provided an update
on H5N1 (Avian influenza). Historically associated with birds and poultry, H5N1 was detected in
cattle in 2024, resulting in over 1,000 affected herds. There have been 70 human cases, primarily among individuals with direct contact with animals. Recent data show a decrease in infections among both non- human mammals and birds, with no new human cases reported in
over 15 weeks. He credited the USDA’s early detection efforts, including bulk milk testing, for
this progress. Dr. Daskalakis concluded by noting that the CDC remains focused on seasonal respiratory virus preparedness, including COVID -19, influenza, and RSV, to ensure Americans
have the tools to prevent these infections.
Dr. Chris Braden, Principal Deputy Director of the National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) provided additional updates on outbreak investigations. NCEZID is currently monitoring several foodborne outbreaks, including Salmonella linked to pistachio cream and eggs, which were detected through the PulseNet system. This system utilizes whole-genome sequencing to identify related cases. Dr. Braden also highlighted a cluster of systemic illnesses in Massachusetts linked to unauthorized Botox injections by an unlicensed provider. The CDC is supporting this investigation by supplying botulinum antitoxin, which is stored at CDC quarantine stations nationwide. Additionally, Dr. Braden noted emerging concerns regarding the New World screwworm, an animal parasite making its way from Central America into Mexico. Although primarily an animal health issue, human cases can occur, resulting in
severe myiasis (infestation of live tissue). CDC is collaborating with the USDA to monitor this situati on, as it poses risks to animal agriculture and, to a lesser extent, human health.
Food and Drug Administration (FDA)
Dr. Tracy Beth Hoeg from the FDA provided several updates. She began by addressing a recent
FDA announcement regarding a safety label change for mRNA COVID -19 vaccines to reflect the
ongoing risk of myocarditis, particularly in males ages 12 to 24. FDA data from 2023 and 2024 identified a myocarditis rate of 27 cases per million in this group. She clarified that this differs
from the CDC’s reported rate of 2 cases per million, as the FDA’s data are more stratified
explicitly by age and sex. Additionally, FDA data showed instances of late gadolinium enhancement on MRI six months post -vaccination, suggesting potential myocardial damage of
uncertain clinical significance. Based on these findings, the FDA implemented the safety label
change.
Dr. Hoeg also noted that the FDA’s Vaccines and Related Biological Products Advisory
Committee (VRBPAC) recommended the JN.1 variant antigen for the 2025 to 2026 COVID -19
vaccine, consistent with the previous year, due to slower viral mutation rates. The FDA has approved two updated vaccines, Numovoxid and MN.X Spike, both with narrowed indications for individuals ages 12 to 64 with at least one risk factor for severe COVID -19, and for adults 65
and older. Both manufacturers have committed to post -marketing randomized controlled trials to
evaluate vaccine efficacy, particularly in adults ages 50 to 64.
Dr. Hoeg also referenced a recent FDA decision to pause use of the live chikungunya vaccine in
adults 60 and older due to reports of 17 adverse events, including two deaths. She concluded by highlighting a study by Albertson et al., published in Infectious Diseases and Therapy , that
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 addresses subclinical myocarditis post -vaccination in individuals ages 5 to 30. This study fulfills
part of a post -marketing requirement and provides additional data on this safety concern.
Indian Health Services (HIS)
Dr. Matthew Clark from IHS provided an update on vaccination efforts in tribal communities. He
emphasized that IHS is working closely with federal, tribal, and urban Indian organization partners to mitigate the risk of vaccine -preventable illnesses among v ulnerable populations. In
alignment with its mission, IHS is committed to raising health status and improving health outcomes in American Indian and Alaska Native communities through a comprehensive approach. This includes promoting healthy lifestyles, supporting traditional culture and healing, providing preventive screenings, and managing both acute and chronic diseases. As a health care system serving 2.1 million American Indian and Alaska Native beneficiaries, vaccination remains a key component of IHS’s strategy. The agency advances this work through proactive education, informed consent, and respect for the values of patients, their families, and the
communities they serve. Dr. Clark noted that tribal communities face unique challenges that
impact access to preventive care, and IHS is actively collaborating with tribal health partners to identify vaccine priorities and establish best practices that meet the specific needs of Indian
Country.
RSV  VACCINES -MATERNAL/PEDIATRIC

D
r. Adam MacNeil (CDC/NCIRD) introduced the Maternal/Pediatric RSV Vaccine Work Group.
RSV is the leading cause of hospitalization in U.S. infants, with most infected in their first year
and nearly all by age two. About 2 to 3% of young infants are hospitalized, and 80% of those have no underlying conditions. All young infants are at risk for severe RSV. Before 2023, no
long- acting preventive products were available.
In 2023, two products to prevent severe RSV in infants were approved by the FDA and
recommended by the CDC and the ACIP. All infants should be protected through either maternal RSV vaccination or a long- acting monoclonal antibody. Pregnant women should receive one
dose of the maternal RSV vaccine between 32 and 36 weeks of pregnancy. Nirsevimab is recommended for infants younger than 8 months entering their first RSV season and for some
children aged 8 to 19 months at increased risk entering their second season.
A new long- acting monoclonal antibody, clesrovimab, is a third option to protect infants from
severe RSV disease. Clesrovimab was approved by the FDA on June 9, 2025, for use in infants born during or entering their first RSV season.
The work group and ACIP have been reviewing data on clesrovimab since September 2024. In
September, the work group reviewed safety and efficacy data from Merck. In October, ACIP reviewed these data along with the work group’s interpretation. From November 2024 through April 2025, the work group reviewed the GRADE assessment and the EtR framework for
clesrovimab.
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 Since the April 2025 ACIP meeting, the work group has reviewed data on the uptake, safety, and
effectiveness of the maternal RSV vaccine and the long- acting monoclonal antibody from the
2024– 2025 season.
Dr. MacNeil shared that the session would include updates on current RSV prevention products,
including uptake, effectiveness , and impact, and safety data for the maternal RSV vaccine and
long- acting monoclonal antibody. The session would also cover the evidence- to-
recommendation framework for clesrovimab, the work group’s interpretations, and clinical
considerations for clesrovi mab.
Dr. Georgina Peacock (CDC/NCIRD) presented on the implementation and uptake of
Nirsevimab and maternal vaccination for infant protection from RSV. Data sources include the
National Immunization Survey, a random -digit-dial cellular phone survey of U.S. adul ts aged 18
and older across jurisdictions and territories; Immunization Information Systems (IIS), which are
confidential, population- based databases that record immunizations administered by
participating providers. CDC funds 64 jurisdictions to operate I IS, which provide monthly
aggregate data for COVID -19, influenza, and RSV, as well as quarterly de -identified line- level
data. The Vaccine Safety Datalink (VSD) provides vaccination coverage estimates based on
electronic health records, including maternal RSV vaccination coverage.
Immunization Information Systems data show monthly administration of nirsevimab to infants
under eight months of age during the 2024– 2025 RSV season. More infants received protection
through nirsevimab in the second season than in the first season, 2023– 2024.
Infants born during the 2023– 2024 RSV season (October to March) typically received
nirsevimab closer to birth, while those born before September received it more than one month after birth. This pattern aligns with the availability and recommendations for nirsevimab, which
typically begin shortly before the RSV season in most states.
During the second season of implementation, more infants born during the RSV season
received nirsevimab within the first month of life compared to the 2023– 2024 season. This
suggests an improved understanding of administration guidance among healthcare providers
and better access to nirsevimab.
From September 2024 through January 2025, 38.5% of pregnant women ages 18 to 49
received the RSV vaccine. Coverage varied by race and ethnicity, ranging from 25.7% among Black pregnant women to 52.6% among Asian pregnant women. These patterns are consisten t
with other vaccines during pregnancy, which typically show higher coverage among Asian and White non -Hispanic women and lower coverage among Black non- Hispanic and Hispanic/Latino
women. Fifty -seven percent of infants born between April 2024 and March 2025 were protected
against RSV through either maternal vaccination or receipt of nirsevimab.
For infants who become eligible, nirsevimab is recommended within the first week of life for those born between October and March in most of the continental United States. Birthing
hospitals play a vital role in ensuring timely administration, especially f or infants without
commercial insurance. Approximately 45% of U.S. children ages 0 to 17 lack commercial
insurance and are less likely to be seen by a primary care provider within one week of birth.
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 Providing nirsevimab in the hospital helps prevent missed opportunities for RSV immunization
and supports coordination of care with pediatricians.
Participation in the Vaccines for Children (VFC) program by birthing hospitals promotes access
to all ACIP -recommended vaccines. It allows newborns to receive necessary immunizations,
such as nirsevimab and hepatitis B, before hospital discharge without up front costs to the
hospital for VFC -eligible children. This supports equitable, high- quality care for all infants at risk
for RSV, regardless of insurance status.
In 2023, only 10% of U.S. birthing hospitals were enrolled in the VFC program when nirsevimab was added to the routine schedule. Through updated policies, new partnerships, and strong
outreach, enrollment has grown to over 1,000 hospitals in under two year s.
For the 2025– 2026 RSV season, the supply of monoclonal antibodies is expected to meet
demand and arrive earlier than in the previous season, supporting broad availability and a
smooth program rollout. CDC is working with state partners, professional organi zations, and the
Indian Health Service to improve access and uptake of both maternal vaccines and infant monoclonal antibodies. Preseason technical assistance is underway to support ordering and logistics. Increased availability of 50 mg doses of nirsevimab is expected early in the season,
and the newly licensed clesrovimab will be available once added to the CDC’s VFC contracts.
Dr. Peacock summarized that during the 2024– 2025 season, more infants born during the RSV
season received nirsevimab within their first month of life compared to the previous year. This
improvement was likely due to greater awareness among healthcare provi ders and families, as
well as better supply availability. Maternal vaccination and RSV monoclonal antibodies
protected 57% of infants born between April 2024 and March 2025, demonstrating the value of offering both options. Increased enrollment of birthing hospitals and improved early supply
should enhance access to RSV protection in the upcoming season.
Dr. Adam MacNeil (CDC/NCIRD) presented the effectiveness and impact of RSV prevention products in infants during the 2024– 2025 season. The CDC utilized data from three primary
networks to evaluate RSV product effectiveness (PE) in the U.S., all based on va riations of the
case -control design. Two networks, VISION and NVSN, used a test -negative design, where
infants with acute respiratory illness who received medical care (emergency department visit, hospitalization, or ICU admission) and were tested for RSV.  Those who tested positive (cases)
were compared to those who tested negative (controls) in terms of their RSV immunization status. The third, the Overcoming COVID -19 Network, used a matched case- control design
comparing RSV -positive children with ICU admi ssions with matched RSV -negative controls. In
all three networks, effectiveness was estimated by comparing the odds of RSV immunization
between RSV -positive and RSV -negative infants. Each network has unique strengths: VISION
uses electronic health records from emergency departments and hospitals in six states, NVSN
conducts active surveillance in seven pediatric academic centers, and the Overcoming Network
collects data from 26 pediatric intensive care units across 23 states.
Each network verified immunization status through electronic health records and immunization
registries; NVSN and the Overcoming Network also included provider records and parental
reports. VISION and NVSN analyzed data from October 2024 to March 2025, whi le Overcoming
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 analyzed data from December 2024 to April 2025. In all platforms, cases were children who
have tested positive for RSV. NVSN systematically tested all enrolled children, including those
who have not undergone clinical testing. Controls were children who tested negative for RSV; in
NVSN, this may have included children without clinical testing. The Overcoming Network
enrolled matched controls based on site, age, and date of hospitalization of cases.
All three studies included infants who were <8 months old on October 1, 2024, or born after that
date during the study period. For maternal RSV product effectiveness, VISION included infants
born on or after September 14, 2024, which is 14 days after vacci ne availability in most of the
U.S., while NVSN included infants under 6 months of age during the study period. All analyses
used multivariable logistic regression, adjusting for site, age in months, and enrollment timing.
VISION analyses also adjusted for  race, ethnicity, and sex. For nirsevimab effectiveness, NVSN
and Overcoming analyses also adjusted for presence of at least one high- risk medical condition.
Overcoming analyses additionally adjusted for the Social Vulnerability Index, and NVSN also
accounted for race and ethnicity and insurance status in the maternal vaccine analysis.
Nirsevimab showed strong effectiveness against RSV -associated emergency department visits
during infants’ first RSV season. In the VISION analysis of over 4,000 ED visits, 79% of RSV -
positive children did not receive nirsevimab, compared to 64% of RSV -negative children. In the
NVSN analysis of nearly 500 ED visits, 86% of RSV -positive children did not receive nirsevimab,
compared to 56% of RSV -negative children. Among immunized children, the median time since
the last dose was 68 days. The adjusted product effectiveness against RSV -associated ED
visits was 63% in VISION and 76% in NVSN, with overlapping 95% confidence intervals,
indicating consistent protection across both networks.
In the VISION analysis of over 600 hospitalizations, 81% of RSV -positive children did not
receive nirsevimab, compared to 55% of RSV -negative children. In the NVSN analysis of nearly
700 hospitalizations, 89% of RSV -positive children had not received nirsevimab, compared to
61% of RSV -negative children. Among those who had received the antibody, the median time
since dose was 61 days in VISION and 52 days in NVSN. The adjusted effectiveness against
RSV-associated hospitalization was 79% in VISION and 82% in NVSN, with overlapping 95%
confidence intervals.
In the VISION analysis of 374 ICU admissions, 86% of RSV -positive infants had not received
nirsevimab, compared to 55% of RSV -negative infants. In NVSN, 92% of RSV -positive infants
did not receive the antibody, compared to 56% of RSV -negative infants. The Overcoming
platform showed similar results, with 87% of RSV -positive infants having not received
nirsevimab versus 56% of RSV -negative infants. Among those who had received nirsevimab,
the median time since dose at ICU admission was 56 days in VISION, 52 d ays in NVSN, and 50
days in Overcoming. Adjusted product effectiveness against RSV -associated ICU admission
was estimated at 82% for VISION, 88% for NVSN, and 88% for Overcoming, with overlapping
95% confidence intervals across all three platforms.
During the 2024– 2025 RSV season in the United States, the effectiveness of the maternal RSV
vaccine against RSV -associated emergency department (ED) visits in infants during their first
season was assessed using data from the VISION platform. Among nearly 1,000 ED visits, 79%
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 of RSV -positive infants did not have evidence of maternal RSV vaccination, compared to 65% of
RSV-negative infants. Among infants whose mothers had received the vaccine, the median
number of days since birth was 53, and the median number of days since maternal vaccination
was 85. The estimated vaccine effectiveness against RSV -associated ED visits was 54%, with a
95% confidence interval of 35% to 67%.
During the 2024– 2025 RSV season, maternal RSV vaccine effectiveness against infant
hospitalization was 79% in the VISION network and 70% in NVSN, with overlapping confidence
intervals. In both networks, over 80% of RSV -positive infants had no documented maternal
vaccination. Among vaccinated groups, the median time since birth was around one month, and
the median time since maternal vaccination was just over 70 days.
When interpreting these real -world product effectiveness findings, it's important to consider that
differences in enrollment and population across systems may limit comparability. While study
design and analysis help control confounders such as health -seek ing behavior, residual
confounding is still possible, although a variety of sensitivity analyses were performed to assess
the influence of known confounders. There is also a risk of misclassifying RSV immunization
status, although multiple data sources wer e used to verify immunization records.
RSV product effectiveness estimates align with clinical trial efficacy data for both nirsevimab and
maternal RSV vaccination, particularly in terms of hospitalization and ICU admissions. Although
ED visits were not measured in clinical trials, the real -world data suggest both products are
effective in preventing RSV -associated emergency visits, hospitalizations, and severe illness.
Ongoing monitoring will be important to evaluate additional outcomes.
To assess the impact of RSV prevention products on pediatric RSV -associated hospitalizations
in the U.S., data were analyzed from two active, population- based surveillance systems. RSV -
NET, part of the RESP- NET system, monitors RSV, influenza, and COVID -19 hospitalizations
across all ages in 13 states. The second system, NVSN, tracks hospitalizations among children
with acute respiratory illnesses across seven U.S. pediatric medical centers.
An ecological analysis was conducted to assess changes in pediatric RSV -associated
hospitalization rates before and after the introduction of RSV prevention products. RSV
hospitalization rates from pre -pandemic seasons (2018– 2020 for RSV -Net, 2017– 2020 for
NVSN) were compared to rates from the 2024– 2025 season, the second year of product
availability. Seasons from 2020– 2023 and 2023– 2024 were excluded due to pandemic
disruptions and limited product uptake, respectively. Weekly and monthly hospitalization ra tes
were analyzed, and cumulative rates were compared across seasons. Rate ratios and relative
rate reductions were calculated to assess the impact of RSV prevention products. Analyses
focused on three age groups with different RSV prevention options: infants 0 –7 months (eligible
for maternal vaccine or nirsevimab), children 8– 19 months (limited eligibility for nirsevimab
based on risk conditions), and children 20– 59 months (not eligible for RSV prevention products,
used as a comparison group).
During the 2024– 2025 RSV season, prevention products were available before the season
began in most states, with coverage increasing over time. By March 2025, nirsevimab coverage
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 among infants aged 0– 7 months ranged from 21% to 48% across reporting jurisdictions. As of
January 2025, 39% of pregnant women aged 18– 49 had received the RSV vaccine.
The ecological analysis compared RSV hospitalization rates among infants (0 to 7 months),
toddlers (8 to 19 months), and preschoolers (20 to 59 months) before and after the introduction
of RSV prevention products. Historically, infants have experienced the  highest hospitalization
rates, followed by toddlers and preschoolers, with rates remaining relatively consistent  within
each age group. During the 2024– 2025 season, new RSV prevention products became
available for infants and some high -risk toddlers, whil e preschoolers remained ineligible for
these products. By comparing changes in hospitalization rates within each age group, the
analysis assessed whether the declines among infants eligible for prevention were greater than
declines in the other two age groups, which would suggest a population- level impact of the new
products.
Results from the analysis showed that the two networks identified over 20,000 RSV -associated
hospitalizations in children under five across the compared periods. In the 2024– 2025 season,
the proportion of children aged <5 years with an RSV -associated hospi talization who were aged
0 to 7 months decreased from 51% to 29% in RSV -NET and from 46% to 38% in NVSN in 2024 -
2025 compared to prior seasons before the introduction of prevention products. The median age at hospitalization also nearly doubled, from 7.7 t o 15.4 months in RSV -NET and from 6.3 to 12.7
months in NVSN. This indicated that children hospitalized with RSV during the 2024– 2025
season were typically older than in prior seasons.
Cumulative adjusted RSV -associated hospitalization rates in the 2024– 2025 season were
compared to those in prior seasons before product introduction across three age groups. Among infants aged 0 to 7 months, rates dropped from 17 to 10.5 per 1,000 in RSV -NET and from 16 to
11 per 1,000 in NVSN, corresponding to a 38% and 31% reduction in hospitalization rates, respectively. No reductions occurred among children aged 8 to 19 months or 20 to 59 months, suggesting the observed decline was limited to the age gr oup eligible for RSV prevention
products.
Among infants aged 0 to 7 months, further analysis showed that RSV -associated hospitalization
rates were reduced by nearly half among those aged 0 to 2 months. In the 2024– 2025 season,
rates among infants aged 0 to 2 months dropped by 47% in RSV -NET and 46% in NVSN
compared to prior seasons.
Dr. MacNeil concluded that two population- based surveillance networks demonstrated
significant reductions in RSV -associated hospitalizations during the 2024– 2025 season among
infants eligible for preventive products, with decreases of 38% and 31% among those aged 0 to
7 months compared to prior seasons before product introduction. The greatest reductions were
observed in infants aged 0 to 2 months, the group at the highest risk for hospitalization,
highlighting the importance of timely protection through maternal vaccination during pregnancy
or the administration of nirsevimab in the first week of life. Ongoing monitoring of RSV disease
trends, including severity and age distribution, remains crucial for evaluating the long- term
impact.
31
 Dr. Levi emphasized the need for more detailed analyses to better understand the impact of
RSV prevention products. He suggested evaluating whether certain groups, such as preterm
infants or those with comorbidities, benefit more than healthy, full -term in fants. He also
recommended assessing broader outcomes, such as all -cause lower respiratory tract infections
and overall respiratory infections, to ensure that reductions are not due to changes in testing
practices. Additionally, he proposed examining hospi talization severity, including length of stay
and type of care provided, to capture the overall clinical benefit better.
Dr. MacNeil acknowledged the importance of reducing all respiratory infections, not just RSV, and emphasized that preventing infant and pediatric hospitalizations is highly valuable. RSV
alone accounts for a large portion of hospitalizations in newborns, s o RSV prevention products
are already having a meaningful public health impact. Regarding more granular analyses, such
as subgroup evaluations, it was noted that these would be useful. Still, limitations in statistical
power may affect the ability to explore them in greater depth.
Dr. Hibbeln noted that combining small -sample clinical trials with large -scale ecological studies
can be a challenging task. Still, it appears that both types of studies show similar effect sizes for RSV prevention products. He asked for confirmation on whether that observation is accurate.
Dr. MacNeil confirmed that although the clinical trials were not conducted in the United States,
and some differences exist, the overall magnitude of effect appears consistent. The observed
real-world impact aligns with expectations based on the clinical t rial results.
Dr. Hibbeln noted that the major event between the two ecological studies was the COVID -19
pandemic and asked whether there is any evidence of an interaction or a potential protective effect of COVID -19 vaccination on RSV hospitalizations or related outcom es.
Dr. MacNeil responded that, biologically, there would not be a direct effect of COVID -19 or
COVID -19 vaccination on RSV, as the two viruses are very different and unrelated in their
mechanisms of infection.
Dr. Malone noted that monoclonal antibodies are particularly vulnerable to viral drift and suggested that it could be beneficial if the two available monoclonals target different epitopes.
He asked whether there is information available on whether these tw o monoclonals are directed
at distinct regions of the virus.
Dr. MacNeil explained that both monoclonal antibodies target the larger prefusion protein.
However, there is a possibility that if resistance develops against one, the other could still offer
protection. This consideration was part of the work group's rati onale and deliberation in
recommending the inclusion of a second monoclonal antibody.
Dr. Malone expressed support for the approach and noted that the discussion highlights the significant viral and infectious pressure currently present. He asked whether there is active
monitoring in place to track changes that could impact the effectivenes s of monoclonal
antibodies due to viral drift.
Dr. MacNeil explained that RSV infects individuals multiple times throughout their lives, resulting
in the continuous circulation of the virus. Because of this, protecting a relatively small population
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 is not expected to create significant population- level selective pressure. He added that while
some genomic monitoring of RSV is conducted, widespread ecological selective pressure is not
anticipated, since the virus continues to be transmitted broadly among the general population.
Dr. Malone noted that drug- drug interactions will be an important issue for ACIP to consider
moving forward. He pointed out that among those receiving monoclonal antibody products,
some infants are likely fully vaccinated under the standard birth schedule,  while others may not
be. If that is the case, he suggested it would be valuable to collect and analyze data comparing
safety and effectiveness between these groups. He emphasized that demonstrating no
difference in outcomes between those who receive standard vaccinations concurrently and
those who do not would be useful if such monitoring is not already in place.
An SME clarified that the two monoclonal antibodies bind to different locations on the virus.
While some viruses are known to drift away from the effectiveness of monoclonal antibodies,
these monoclonals are likely less prone to such drift due to the virus 's evolutionary
characteristics. However, genetic surveillance is ongoing to monitor changes and ensure
continued effectiveness.
Dr. Levi emphasized the importance of monitoring how vaccine efficacy changes over time, even within a single season. Referring to the maternal RSV vaccine data, he noted that between
days 180 and 360, a signal appeared suggesting negative efficacy, with m ore hospitalizations
occurring among vaccinated individuals compared to those who were not vaccinated. He
acknowledged that RSV is a challenging virus that often responds unpredictably to interventions
and stressed the need for careful interpretation and a deeper understanding of potential
explanations for these findings.
Dr. MacNeil acknowledged that the effectiveness of RSV prevention products wanes over time. He emphasized that the goal is to protect infants during their most vulnerable period, particularly
in the first two months of life, before their immune systems are fully developed. By providing
protection early, the aim is to help children reach an age where, like healthy teenagers or adults,
they may still get infected with RSV but are far less likely to develop severe disease. The
primary objective is to reduce the risk of serious outcomes during the earliest and highest -risk
stage of life.
Dr. Picaro addressed the question about monitoring protection beyond 150 days, explaining that the current challenge stems from the way these products are administered, typically at the
beginning of the RSV season. As coverage increases over time, the number of children who have reached 120 to 180 days post -immunization during the observation period decreases. This
limits the ability to assess long -term protection in current analyses. He noted that this challenge
is tied to the seasonal nature of product rollout. However, he expressed hope that data from regions where RSV circulates more consistently throughout the year may help answer questions
about the duration of protection.
Dr. Malini DeSilva (HealthPartners) shared updates on prenatal RSVpreF vaccine safety.
Established in 1990, the Vaccine Safety Datalink (VSD) is a collaborative project between CDC's Immunization Safety Office and integrated healthcare organizations in the  United States.
The VSD primarily monitors vaccine safety through observational, multi -site studies that utilize
33
 real-world data. It includes data on approximately 15.5 million individuals annually, representing
about 4.5% of the U.S. population, with an annual birth cohort of roughly 115,000 live births.
Data are organized using a common data model with standardized coding systems. Currently,
13 VSD sites provide clinical, methodological, and data expertise, with 11 of those sites
contributing data.
The prenatal RSV vaccine was recommended for use by the ACIP in September 2023 for
administration between 32 and 36 weeks of gestation, with seasonal use from September
through January. In the phase 3 RSVpreF clinical trial, non -significant imbalances were
observed among vaccinated women compared to placebo recipients in rates of preterm birth,
gestational hypertension, and preeclampsia.
Prenatal RSVpreF vaccine safety outcomes evaluated in this study included acute outcomes
occurring within 42 days of vaccination. These outcomes were preterm birth, small for
gestational age at birth, stillbirth, and hypertensive disorders of pregnancy. Hy pertensive
disorders were assessed both as a combined outcome and as individual conditions, including
gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome.
A target trial emulation design was used to compare RSVpreF -vaccinated and unvaccinated
pregnant women at each gestational week, aiming to mimic a randomized trial using
observational data. The study included pregnant women aged 16– 49 years with a gestational
age of 32 to less than 37 weeks between September 22, 2023, and January 31, 2024 (or
February 29, 2024, for two sites). Vaccinated individuals were matched one- to-one with
unvaccinated individuals by site and likelihood of vaccination, based on the sam e gestational
week. Outcomes were tracked from the index date through two weeks after pregnancy ended. Unvaccinated matches were assigned the same index date as their vaccinated counterpart, and
pairs were censored if the unvaccinated individual later received the vaccine.
Risk ratios with 95% confidence intervals were estimated using a log- binomial model with robust
variance, adjusting for nulliparity. For small -for-gestational -age infants at birth, matched sets
were excluded if infant weight was missing for either infant. For hypertensive disorders of
pregnancy, matched sets were excluded if disease onset occurred on or before the index date
for either pregnant woman.
The analysis included 13,966 matched pairs; however, the cohort does not represent unique
individuals, as some initially unvaccinated participants were later vaccinated and subsequently
rematched. While overall characteristics were similar, RSV -vaccinated women were generally
older than their unvaccinated matches. The vaccinated group had a higher proportion of Asian
patients and a lower proportion of Black and Hispanic patients. Additionally, 98.5% of the
vaccinated group had received at least one other vaccine during pregnancy, compared to 81%
in the unvaccinated group. A higher percentage of nulliparous women was also observed in the
vaccinated group.
The analysis found no significant differences in the risk of acute safety outcomes between
RSVpreF -vaccinated pregnant women and their unvaccinated matches across all evaluated
time intervals (1 –6 days, 1– 21 days, and 1– 42 days).
34
 The analysis found no association between RSVpreF vaccination during pregnancy and the risk
of preterm birth, small for gestational age at birth, or stillbirth. However, there was a statistically
significant association between RSVpreF vaccination and hypertensive disorders of pregnancy.
The adjusted risk ratio for any hypertensive disorder was 1.09, with significant associations
observed for both preeclampsia and gestational hypertension.
Among individuals with diagnosed hypertensive disorders of pregnancy, rates of cesarean
delivery and post -birth hospitalization admissions were similar between RSVpreF- vaccinated
and unvaccinated groups. Lengths of stay over 3 days were slightly higher in the vaccinated
group, except for infants delivered by cesarean. Overall, the findings suggest comparable
severity of hypertensive disorders of pregnancy between the two groups.
In the phase 3 clinical trial of the RSVpreF vaccine administered during pregnancy, there were
more cases of gestational hypertension and preeclampsia among vaccine recipients compared
to placebo recipients. However, these differences were not statisticall y significant.
A retrospective observational cohort study of patients who delivered at 32 weeks and 0 days
gestation or later at two New York City hospitals between September 22, 2023, and January 31, 2024, found a significant association between RSVpreF vaccination and hypertensive disorders
of pregnancy using a time- dependent Cox regression model. However, this association was not
significant in either unadjusted or adjusted multivariable logistic regression models. In stratified
analyses by site and insurance status, t he association persisted only among patients with
private insurance and at one of the two hospitals.
Dr. DeSilva concluded that the RSVpreF vaccine is not associated with increased risk for acute safety outcomes, preterm birth, small for gestational age at birth, or stillbirth. However, the vaccine is associated with a small but statistically significant increased risk for hypertensive
disorders of pregnancy. These findings are consistent with results from the Phase 3 clinical trial
and a large observational study; however, the association may be influenced by residual
confounding or outcome misclassificat ion. Importantly, the severity of hypertensive disorders
appeared similar between vaccinated and unvaccinated individuals based on rates of cesarean
delivery, post -birth hospital admissions, and length of stay. Results from the 2024– 2025 season
are pending and will provide additional insight into the safety of the prenatal RSV vaccine.
Dr. Matthew Daley (Kaiser Permanente Colorado) presented on monitoring the safety of nirsevimab in infants born through <8 months. Nirsevimab is a long- acting monoclonal antibody
recommended for the prevention of RSV disease in infants. It is intended for infants from birth to
under 8 months of age who have not received the RSV vaccine during pregnancy, as well as for
select high- risk infants aged 8 to 19 months. Phase 3 clinical trials demonstrated high efficacy,
and post -licensure data showed strong effec tiveness. Although there was a severe shortage
during the 2023– 2024 season, uptake remained high within the VFC and VSD populations. A
total of 72 percent received either nirsevimab or the maternal RSV vaccine.
The safety profile of nirsevimab is based on three randomized clinical trials, which included both
healthy and high- risk infants. Across these trials, 3,184 infants received nirsevimab, 1,284
received a placebo (with a 2- to-1 randomization), and 304 receiv ed palivizumab, another
monoclonal antibody targeting RSV. Adverse events were generally balanced between the
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 nirsevimab and comparator groups. Seven infants who received nirsevimab experienced
rashes, primarily papular or maculopapular in nature. Importantly, no cases of anaphylaxis,
serious hypersensitivity reactions, or immune complex diseases were reported.
Although clinical trials provided important safety data, additional post -licensure monitoring is
needed to assess rare adverse events and evaluate safety when nirsevimab is administered
during routine care in the general population. The objective of this study was to examine the safety of  nirsevimab by analyzing prespecified adverse events among recipients in the Vaccine
Safety Datalink (VSD). While nirsevimab is a passive immunization, the CDC and ACIP
specifically requested that the VSD evaluate its safety.
The VSD is an observational system that utilizes EHR data from a birth cohort of approximately
115,000 individuals annually. It integrates data from electronic health records, claims, immunization registries, and diagnosis codes across inpatient, emergency , and outpatient
settings. A key strength of VSD is its ability to conduct rapid manual medical record reviews to
validate diagnoses and ensure accuracy. It also uses advanced analytic methods, including self -
controlled designs, to address confounding.
During the 2023– 2024 season, 36,719 infants received nirsevimab in the VSD. Prespecified
adverse events were monitored using a self -controlled risk interval analysis, with results
stratified by age group. No increased risk was identified for seizures, ITP,  drug reactions, fever,
or sepsis. No cases of anaphylaxis were reported. Some non -anaphylactic allergic reactions,
primarily hives, occurred on the same day as administration. This finding is consistent with
those from the clinical trials.
For the 2024– 2025 season, this analysis included all VSD -contributing sites and focused on
infants from birth to under 8 months of age who received nirsevimab between October 1, 2024,
and February 1, 2025. All exposed infants were included, regardless of w hether they received
vaccines on the same day. Continuous health insurance enrollment through the control window
was required to track both nirsevimab administration and potential adverse events. A self -
controlled risk interval design was used. Infants whose mothers received an RSV vaccine during
pregnancy were excluded from the study.
Self-controlled designs, such as the self -controlled risk interval, are commonly used in vaccine
safety studies. These methods compare the risk of adverse events during a period shortly after
vaccination with that of a later period in the same individual. This controls for fixed
characteristics, such as chronic conditions, that could bias the results. These designs are useful
because people who receive vaccines often differ from those who do not, and those differences
may not be fully captured in health rec ords.
Age was a significant factor in the design of this study. Diagnoses in the first month of life often
reflect conditions related to pregnancy, delivery, or newborn care. Healthcare use and insurance
enrollment patterns also differ in this period. Additional ly, except for the birth dose of hepatitis B,
routine vaccines are not given before 38 days of age. For these reasons, safety analyses were
done separately for newborns (0 to 37 days) and older infants (38 days to 8 months).
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 The study assessed seizures, immune thrombocytopenia (ITP), drug reactions, fever, and
sepsis using self -controlled risk interval designs. Anaphylaxis and non- anaphylactic serious
allergic reactions were monitored by tracking case counts. Autoimmune and im mune complex
diseases are also planned for evaluation through a case- control study at the end of surveillance,
as these outcomes are rare in infants and may have a delayed onset.
A total of 117,427 neonates and infants from birth to under 8 months of age were identified. Following enrollment criteria, 43,532 received nirsevimab. Exclusions included 1,663 infants
with prenatal exposure to RSV vaccine, as some may still qualify for nirsevimab under specific
clinical circumstances. Additional exclusions were made for infants who received nirsevimab at
the end of the 2023– 2024 season. The final safety analysis included 9,855 neonates (0 to 37
days old) and 28,054 infants (38 days to under 8 months old).
Nirsevimab was administered to infants at various ages from birth to under 8 months, with no
single peak age. Dosing clustered in the first week of life and at typical well -child visit intervals,
including 2 weeks, 2 months, 4 months, and 6 months of age.
Among neonates aged 0 to 37 days, administration frequently occurred on the day of birth, often
with the hepatitis B vaccine. On day one, most neonates received nirsevimab alone, though
some also received hepatitis B. For the remainder of the neonatal peri od, nirsevimab was
typically given without same- day hepatitis B vaccination.
Among neonates aged 0 to 37 days, nirsevimab was often administered on the same day as the hepatitis B vaccine, particularly on the day of birth. Among infants aged 38 days to under 8
months, 84 percent received nirsevimab on the same day as other vaccines . The most common
same- day combination included nirsevimab with hepatitis B, rotavirus, DTaP, Hib,
pneumococcal, and polio vaccines.
No significant increased risk of seizures was observed in either the 2023– 2024 or 2024– 2025
seasons. Medical record reviews showed that some reported cases were not true seizures,
while others were related to known genetic seizure disorders.
Regarding ITP, a single case was identified within the risk window among infants aged 38 days to under 8 months. No cases were observed in the neonatal group.
With respect to drug reactions, there were zero cases in both the risk and control windows for both the neonatal group and the older infant group.
Among neonates aged 0 to 37 days, there were four cases of sepsis or fever in the risk window
and nine in the control window, yielding a relative risk of 0.44. This outcome was not evaluated
in older infants due to differences in clinical management of fev er by age. An exploratory
analysis showed a numerical imbalance in sepsis workups, such as blood or spinal fluid
cultures, between risk and control windows. However, medical record review found no
consistent concerns, with cultures often performed for reas ons other than fever. No increased
risk of sepsis or fever was identified.
For anaphylaxis, no cases were reported in either the neonatal group (0 to 37 days) or the older
infant group. For non- anaphylactic serious allergic reactions, there were 14 cases in the
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 neonatal group and 4 in the older group. These were primarily diagnosis codes for urticaria
(hives) occurring on the same day as nirsevimab administration.
Dr. Daley summarized that among a combined population of 74,000 neonates and infants
exposed to nirsevimab over two seasons, there was no increased risk of seizures, ITP, drug
reactions, fever, or sepsis. No cases of anaphylaxis were reported. A small number of non-
anaphylactic allergic reactions were observed, primarily coded as urticaria or hives, without more serious hypersensitivity in the same children. These findings support a reassuring safety
profile for nirsevimab in routine clinical practice. Addi tional data collection is underway for later -
season use, so these results should be considered preliminary.
Nirsevimab safety surveillance is ongoing. Three assessments were planned: post -2023– 2024
results (already shared with the ACIP RSV Work Group), a preliminary 2024– 2025 assessment
(presented here), and a final cumulative analysis through July 2025. Medical  records will be
manually reviewed for any cases of anaphylaxis or other outcomes of concern. A case -control
study of autoimmune and immune complex diseases was also planned, but only two cases were
identified in 2024– 2025, both related to isoimmunization and not associated with nirsevimab. As
a result, this analysis could not be conducted, but the absence of cases is reassuring.
Dr. Adam MacNeil (CDC/NCIRD) shared the updates and summary of the Evidence to
Recommendation (EtR) framework for clesrovimab. The policy question under consideration is
whether clesrovimab should be recommended for all infants under 8 months of age born during
or entering their first RSV season.
For the public health problem domain, Dr. MacNeil shared that RSV places a significant burden
on young children. Without preventive products, the CDC estimates RSV caused approximately 2 million medical visits, 58,000 to 80,000 hospitalizations, and 100 to  300 deaths annually in
U.S. children under five. Most infants are infected in their first year of life, with 2 to 3 percent of
young infants hospitalized. Hospitalization risk is highest in the first months of life and declines with increasing age. About 80 percent of children hospitalized for RSV have no underlying medical conditions; therefore, all young children are at risk for hospitalization. When asked if
RSV disease  among  infants <8 months of age is of public health importance, the work group
unanimously voted “yes.”
The benefits and harms domain addressed three key questions: 1) the magnitude of anticipated
benefits; 2) the magnitude of anticipated harms; and 3) whether the benefits outweigh the
harms. To assess this, a GRADE analysis was conducted to evaluate the cer tainty of evidence
for both beneficial and harmful outcomes. The PICO components (population, intervention,
comparison, outcomes) were defined as follows: the population included all infants under 8
months of age born during or entering their first RSV season; the intervention was clesrovimab;
the comparison was a placebo. Beneficial outcomes assessed included RSV -associated
medically attended lower respiratory tract infections (LRTIs), hospitalizations, ICU admissions,
all-cause medically attended LRTIs, and all -cause LRTI -associated hospitalizations. The
harmful outcome evaluated was serious adverse events.
For RSV -associated medically attended lower respiratory tract infection (LRTI), the efficacy was
60%. In the certainty assessment, there was concern for indirectness because the trial excluded
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 infants eligible for palivizumab and was conducted during a season with disrupted RSV
circulation due to COVID -19. This concern was noted for all outcomes but was deemed not
serious. For RSV -associated LRTI with hospitalization, the efficacy was 91%. For R SV-
associated LRTI with ICU admission, the efficacy was estimated to be 100%. There was serious concern for imprecision as the confidence interval contained estimates for which different policy
decisions may be considered.
For harms, the relative risk of serious adverse events was evaluated through 365 days in the
trial. The estimated relative risk was 0.93, with a 95% confidence interval ranging from 0.77 to
1.2, which included 1, suggesting that serious adverse events occurred at a similar proportion in
those who received clesrovimab and those who did not. However, there was a serious concern
for imprecision in this estimate, as too few infants were included to capture rare serious adverse
events.
GRADE findings showed that clesrovimab was effective in preventing RSV -associated medically
attended LRTI and RSV -associated hospitalization, with high certainty. It was effective in
preventing ICU admissions due to RSV -associated LRTI with moderate certai nty. It was not
effective in preventing all -cause medically attended LRTI, with moderate certainty, but was
moderately effective in preventing all -cause LRTI -associated hospitalization, with high certainty.
No increase in serious adverse events was observed in the clesrovimab group compared to the placebo group with moderate certainty.
Beyond trial outcomes, additional benefits of having a second long- acting monoclonal antibody
option include: having another product with a different binding site in case of resistance
mutations, supply shortages, and pricing competition. Rates of injection site and systemic reactions were similar between groups (29.9% for clesrovimab vs. 30.9% for placebo), mostly mild or moderate. Fever rates were also similar (3.7% vs. 4.0%), suggesting no increased risk
with clesrovimab.
Based on the data presented, the work group concluded that clesrovimab is an effective long-acting monoclonal antibody for preventing severe RSV disease in young infants during their first
RSV season. As the second approved product of its kind, it may be helpful in mitigating any
supply disruptions and potential resistance to any single product. Clesrovimab demonstrated a favorable safety profile, with no increase in serious or solicited adverse events, including fever.
However, rare events may not have been detected due to the trial's size. The majority of the
work group agreed that the anticipated benefits were large and the harms minimal. The group
unanimously concluded that the benefits outweigh the risks.
For the values domain, data was presented on parents' and caregivers' views of the benefits of
clesrovimab relative to its harms. A national survey conducted from December 2022 to January
2023 among pregnant and postpartum women found that 31% knew a baby hospitalized with RSV, 38% believed their baby would become moderately or severely ill if infected, and 69%
were concerned about possible hospitalization. In a study conducted in April and May in
Cascadia on parental preferences for RSV products, 37% preferred maternal vaccination, 12% preferred the infant monoclonal antibody, 3% preferred neither, and 48% had no preference,
suggesting that either option may be acceptable to parents. Preliminary data from the National
39
 Immunization Survey showed that as of February, 50% of infants under 8 months had received
a long- acting monoclonal antibody, and another 7% of caregivers reported definite intentions to
do so.
The work group felt that parents and caregivers probably viewed the desirable effects of
clesrovimab as large relative to the undesirable effects. When asked whether there was
important uncertainty or variability in how much parents and caregivers value the prevention of severe RSV disease, the majority of the work group felt there was probably not significant
uncertainty or variability.
In the acceptability domain, data assessed whether clesrovimab is acceptable to key
stakeholders, primarily providers and professional organizations. In a survey of 200 U.S.
pediatricians conducted in October 2024, about 75% reported offering a long- acting monoclonal
antibody in their practice. Over 90% agreed or strongly agreed that it is safe for infants, effective
against severe RSV disease, and that they felt confident recommending and co- administering it
with other vaccines. National organizations, inc luding the American Academy of Pediatrics, the
American Academy of Family Physicians, and the National Foundation for Infectious Diseases,
have endorsed clesrovimab. The majority of the work group felt that clesrovimab is acceptable
to key stakeholders. A minority of the work group said it is probably acceptable.
In the feasibility domain, the data focused on whether clesrovimab is practical to implement for
all infants under 8 months of age born during or entering their first RSV season. If recommended by ACIP, clesrovimab would become the second long- acting monoc lonal
antibody included in the Vaccines for Children (VFC) program, which provides vaccines at no cost to eligible children. The product is a single- dose immunization, administered regardless of
infant weight, which may simplify delivery. However, stocking could be a challenge for providers
who also need to carry nirsevimab for high- risk children aged 8 through 19 months. Some may
prefer to stock only one long- acting RSV monoclonal antibody. In a 2024 survey of pediatricians,
the most frequently reported im plementation challenges were determining maternal RSV
vaccination status (34%), the financial burden of purchasing the product, and reimbursement issues from private insurers. The majority of the work group felt that clesrovimab is, or probably
is, feasible to implement.
For the resource use domain, a cost -effectiveness model was developed by the University of
Michigan and the CDC, building on methods previously used to evaluate nirsevimab. The model
was updated with key inputs for clesrovimab, including its effectiveness and anticipated cost per dose. In the base case scenario, assuming 50% coverage of clesrovimab among an annual
birth cohort and continued use of palivizumab for eligible high- risk infants, the model estimated
prevention of approximately 120,000 outpatient visits, 43,500 emergency department visits,
20,000 hospitalizations, 4,500 ICU admissions, 20 deaths, and nearly 3,500 quality -adjusted life
years (QALYs) gained.
Estimated incremental cost -effectiveness ratios were roughly $3,000 per outpatient visit
prevented, $8,200 per emergency department visit prevented, $17,500 per hospitalization prevented, $80,000 per ICU admission prevented, and $104,500 per quality -adjusted  year of life
(QALY)  gained. Extensive sensitivity analyses were conducted using a wide range of input
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 values. Results were sensitive to assumptions about inpatient costs, quality of life losses, and
product price.
The majority of the work group felt that clesrovimab use among all infants under 8 months of
age born during or entering their first RSV season is, or probably is, a reasonable and efficient
allocation of resources at an average cost of $458 per dose.
Dr. MacNeil summarized the work group’s discussion, considerations, and interpretation of the
data. The group found that the phase 2b/3 trial of clesrovimab demonstrated high efficacy in
preventing severe RSV through 150 days. Serious adverse events appear ed to be balanced
between the clesrovimab and placebo groups, although rare events may not be detectable in a trial of this size. The group noted that while clesrovimab has a shorter half -life than nirsevimab,
its efficacy appeared sustained through 150 days. Direct comparisons between the two products
are limited due to differences in trial endpoints; a head- to-head study would be needed to
evaluate comparative efficacy.
The group emphasized the value of having multiple long- acting monoclonal antibody products
and manufacturers, as this diversification supports resilience in the face of potential resistance or supply shortages and may help drive price competition. RSV remains the leading cause of
hospitalization in infants, and immunization can significantly reduce this burden. To achieve a
meaningful public health impact, timely administration is critical. For infants born outside the
RSV season, high coverage before the s eason begins is essential. For those born during the
season, administration should ideally occur within the first week of life, preferably during the
hospitalization for birth.
When asked about the balance between desirable and undesirable effects, the work group
concluded that the desirable consequences clearly outweigh the undesirable ones. In the final
poll, the work group unanimously supported recommending clesrovimab for all  infants under 8
months of age born during or entering their first RSV season.
Dr. Adam MacNeil (CDC/NCIRD) shared the updates on clinical considerations for clesrovimab.
To summarize the effectiveness, uptake, and impact data: Nirsevimab was effective in
preventing RSV -associated emergency department visits, hospitalizations, and cr itical illness
among infants in their first RSV season. Maternal vaccination was effective against RSV -
associated emergency visits and hospitalizations. An estimated 50% of infants were either born
to a vaccinated mother or received nirsevimab. Following t he introduction of RSV immunization,
hospitalization rates declined by 30% to 40% among eligible infants and by 50% among infants
aged 0 to 2 months.
The work group noted that the impact of RSV immunizations in reducing severe disease among
infants during the 2024– 2025 season in the RSV -NET and NVSN networks is clear. Increasing
uptake is crucial to further reduce the burden of RSV. A greater impact has  been observed in
countries with higher immunization coverage. Maximizing availability, including providing the
infant RSV antibody during the birth hospitalization, is important. Expanding birthing hospital
enrollment in the VFC program is a crucial step,  although challenges remain, and continued
efforts are necessary to increase participation.
To summarize the FAERS post -marketing data for nirsevimab: Since approval through March
31, 2025, the most frequently reported adverse events involved RSV infections occurring after
nirsevimab administration, including related symptoms and complications. N o new safety
41
 labeling updates have been made since the addition of serious hypersensitivity reactions on
February 23, 2024. No additional safety signals have been identified. Errors involving incorrect
dosing or product selection continue to be reported. FDA will conti nue routine
pharmacovigilance for nirsevimab.
The VSD nirsevimab safety study for the 2024– 2025 season included nearly 40,000 infants and
employed a self -controlled risk interval design. No increased risk was observed for seizures,
immune thrombocytopenia, drug reactions, sepsis, or fever. No cases of  anaphylaxis were
reported, and 18 cases of allergic reactions, primarily hives, were identified.
The work group found that FAERS and VSD safety data are reassuring and emphasized the
importance of continued safety monitoring.
The VSD maternal RSV vaccine study included a matched cohort of 14,000 pregnant women
who were either vaccinated or unvaccinated. No increased risk was observed for most
outcomes. An association was identified between maternal RSV vaccination and hypertens ive
disorders of pregnancy, including preeclampsia, although the severity of the episodes of
hypertensive disorders of pregnancy was similar among vaccinated and unvaccinated. VSD
noted potential residual confounding, such as parity, and possible outcome m isclassification due
to challenges in determining the timing of onset and the absence of medical chart review.
The work group found the overall study findings reassuring, particularly the lack of association between maternal RSV vaccination and preterm birth. The group continued to conclude that the
benefits of maternal RSV vaccination clearly outweigh the potential risks. Opinions were divided
on the importance of the observed association with hypertensive disorders of pregnancy. Some
members were not concerned, noting the small effect size, the absence of an increase in
severity among vaccinated individuals, and t he lack of association with preterm birth. The
American College of Obstetricians and Gynecologists agreed with this assessment. Some were
concerned that an imbalance of HDP was seen in multiple studies (phase 3 clinical trial,
published retrospective cohor t study, post -marketing study), and felt it was important that
healthcare providers discuss the potential risk of HDP with pregnant women.
Clesrovimab is a long- lasting monoclonal antibody manufactured by Merck and is a form of
passive immunization. It is administered as a single 105 mg dose in a 0.7 mL prefilled syringe,
with the same dose recommended for all infants born during or entering their first RSV season,
regardless of weight.
Dr. Adam MacNeil (CDC/NCIRD) presented the proposed recommendations. Clesrovimab and
nirsevimab are recommended for use in infants under 8 months of age who are born during or
entering their first RSV season. There is no preferential recommendation between the two
products.
Only nirsevimab is recommended for children aged 8 through 19 months who are at increased
risk of severe RSV disease and entering their second RSV season. Infants eligible for
nirsevimab in their second season may have received either clesrovimab or nirsev imab during
their first season. There are no safety or effectiveness concerns with using clesrovimab in the
first season and nirsevimab in the second.
The proposed use of RSV antibody immunizations in infants, including nirsevimab or
clesrovimab, is largely consistent with current nirsevimab recommendations. One dose is
recommended for infants under 8 months of age during or entering their first RSV seas on,
typically October through March in most of the continental U.S., if the mother did not receive RSV vaccine during pregnancy, if maternal vaccination status is unknown, or if the infant was
born less than 14 days after maternal vaccination. Use may also be considered for infants born
to mothers with reduced immune response or impaired antibody transfer, or for infants with
42
 conditions that lead to loss of maternal antibodies, or infants with substantially increased risk for
severe RSV disease.
To prevent severe RSV in infants, most will not need both maternal vaccination and an RSV
antibody. Pregnant women should work with their healthcare provider to choose one of the two
options.
Maternal RSV vaccine is recommended from September through January, and infant RSV
antibodies are recommended from October through March. For infants already born before
October, the optimal time to administer RSV antibody is just before the start of the s eason. In
areas with varying RSV seasonality, providers should follow guidance from their state, local, or
territorial health authorities.
Administration errors have occurred, including the incorrect distribution of RSV immunization
products to the wrong population. Only RSV antibodies should be given to infants. RSV
vaccines, such as Abrysvo, Arexvy, and mResvia, should not be administered t o children. Only
Abrysvo is approved for use in pregnant women. Arexvy and mResvia should not be given
during pregnancy. Older adults may receive any of the three approved RSV vaccines. RSV
antibodies should not be administered to pregnant women or older adults.
If an infant or child receives either nirsevimab or clesrovimab, palivizumab is not recommended
during the same RSV season. Clesrovimab will be administered in the same manner as
nirsevimab, as an intramuscular injection into the vastus lateralis muscle of  the anterolateral
thigh. The gluteal muscle should not be used for administration. It is acceptable to administer
infant RSV antibodies concurrently with routine vaccines.
Clesrovimab should be stored in a refrigerator and used within 48 hours of being removed. It should not be frozen, shaken, or exposed to light.
If RSV antibodies are administered alone, suspected adverse events should be reported to
MedWatch. If they are given at the same time as any vaccine, suspected adverse events should
be reported to the VAERS. Additional reporting to MedWatch is not necessar y in that case.
Proposed Recommendation:
ACIP recommends that infants aged<8 months born during or entering their first RSV
season who are not protected by maternal vaccination receive one dose of clesrovimab.
Dr. Georgina Peacock (CDC/NCIRD) shared updates on the RSV vaccines VFC resolution. The
purpose of the resolution is to update the existing policy to include an additional long- acting
monoclonal antibody for the prevention of RSV.
The first component of the resolution addresses the RSV maternal vaccine. There are no
changes to the eligible groups, recommended schedule, or dosing intervals. However, the name
of the individual product has been replaced with a product group name to ref lect the availability
of two licensed products. There are also no changes to the dosage, contraindications, or
precautions.
The second component of the resolution has been retitled to reflect a product group name
instead of a specific product. The eligible groups remain unchanged, as does the list of children at increased risk for severe RSV disease. The recommended schedule an d intervals for
nirsevimab are unchanged. A new row has been added to the table to include clesrovimab, the newly licensed long- acting monoclonal antibody for RSV prevention. As noted, clesrovimab is
not indicated for use during a second RSV season.
43
 Table notes have been added to define long -acting monoclonal antibodies and to provide a link
to published information on the timing of administration. The language below the table has also
been updated to reference the product group rather than an individual product. There are no
changes to dosage, contraindications, or precautions.
Finally, ACIP recommendations published within six months of the resolution will be incorporated by reference, except for changes related to eligible groups.
Proposed Recommendation: VFC update
 Approve the updated Vaccines for Children (VFC) resolution for prevention of RSV .
Dr. Levi acknowledged the consensus that RSV is a serious illness, particularly for young infants
and those with underlying health conditions or born preterm. He expressed hope that newly
developed RSV therapies will help prevent severe outcomes, including hospitalizations and
deaths. However, he raised concerns based on clinical trial data related to the safety of these
products. In the Melody trial, which tested nirsevimab in healthy infants, there were five deaths
in the immunized group and none in the placebo group. Although serious adverse events
(SAEs) were balanced overall, nervous system -related SAEs appeared more frequently in the
immunized group. He noted that two deaths due to gastroenteritis in healthy infants were
particularly unusual. In the Medley trial, which involved high- risk infants and compared
nirsevimab to palivizumab, the imbalance in deaths continued (five in the immunized group
versus one in the comparator group), with similar patterns in nervous system SAEs and gastroenteritis cases.  The Harmony trial, conducted in Europe, showed no deaths in either
group but still reflected a higher rate of SAEs in the immunized group, particularly involving the nervous system. Dr. Levi also highlighted data from the clinical trial of clesrovimab, the product under current consideration. In that trial, there were seven deaths in the immunized group compared to three in the control group. Nervous system SAEs were reported in 25 immunized
infants versus four in the control group, and gastroenteritis cas es occurred in 30 versus 10
infants. He pointed out the higher dose used for clesrovimab (105 mg) compared to nirsevimab
(50 to 100 mg), suggesting the need to examine potential dose -related effects. Additionally,
early reports from the Melody trial sugges ted that immunized infants had longer hospital stays
upon admission, raising concerns about the potential for immunization- enhanced disease. Dr.
Levi concluded by asking whether these patterns, though based on small numbers, might signal potential safety c oncerns. He noted that post -marketing analyses presented so far have been
limited in scope and duration, and he urged CDC and committee colleagues to consider whether
the observed imbalances warrant further investigation alongside the recognized benefits.
A representative from Merck Research Laboratories spoke about clesrovimab, a monoclonal
antibody recently licensed by the FDA for the prevention of RSV disease in infants entering their first RSV season. The representative explained that the FDA conducted a thorough review of the product’s safety and efficacy data and that Merck had shared detailed materials with the
ACIP working group during its deliberations in November of the previous year. They emphasized
that all adverse events reported during the clinical trials were extensively evaluated, and none were found by investigators to be related to RSV or the intervention given to the infants. No patterns or trends were observed in terms of cause, affected organ systems, or timing of events.
The representati ve also pointed out that the main trial in healthy infants, known as Protocol 4 or
44
 CLEVER, used a 2:1 randomization ratio, which should be considered when interpreting event
numbers.
A member of the Maternal/Pediatric Workgroup addressed concerns about deaths observed in
the pivotal Phase 2b/3 trial of clesrovimab. They noted that deaths were evaluated as potential
harm over the 365 days following immunization. The events were balanced  between the
clesrovimab and placebo groups when accounting for the study's 2:1 randomization ratio.
Specifically, there were seven deaths in the clesrovimab group and three in the placebo group,
which aligns with the expected distribution based on the tri al design. No patterns were observed
in the cause or timing of deaths that suggested a link to the intervention.
An ex officio member clarified that clesrovimab was approved by the Center for Drug Evaluation
and Research (CDER). As someone who works within CDER, they explained that they preferred not to speak on behalf of the review team and instead suggested deferri ng to CDER for an
official comment on the safety review.
Ms. Hodowanik stated that she did not have much to add beyond Merck’s summary but emphasized that the FDA carefully reviewed all case narratives. She confirmed that no trends or clustering were observed in the causes of death, and there was nothing to suggest a drug -
related cause in any of the cases. She also noted that clesrovimab is a monoclonal antibody
and that this class of products is generally well tolerated with limited toxicity.
Dr. Levi thanked the group for their responses and acknowledged the 2:1 randomization ratio
used in the trials. However, he raised a concern about a possible trend in the data. He noted
that across four separate trials, the number of deaths consistently oc curred more frequently in
the immunized groups. While he agreed that the trials were small and not powered to detect
most safety signals unless those signals were very strong, he questioned whether seeing a
similar pattern across multiple studies involving two similar products should prompt further
consideration. He asked the group for their thoughts on whether this recurring outcome might be
meaningful.
Ms. Hodowanik responded by acknowledging that the numerical counts of deaths in the studies
appeared higher in the immunized groups. Still, she emphasized that the actual percentages
were very close, at 0.3% versus 0.2%. She stated that this would not be c onsidered a
meaningful difference in death rates between the study arms. She noted that these are very
small numbers and do not indicate a significant trend. Additionally, she explained that the FDA
placed significant weight on reviewing the narratives of each case and assessing the potential biological plausibility between the causes of death and the administration of clesrovimab. No
such connections were identified in their review.
Dr. Kulldorff commented that among the four trials discussed, three involved nirsevimab, which
has already been recommended by ACIP and is not under consideration for a vote in the current
meeting. He noted that the observed imbalances in those trials are important and should be
closely monitored moving forward, particularly regarding mortality and other potential adverse
events associated with nirsevimab. He clarified that the current vote pertains to clesrovimab, and based on the data presented, mortality  appeared to be more balanced between the study
arms for this product. Dr. Kulldorff suggested that it is possible clesrovimab may prove to be
45
 superior to nirsevimab, although this is not yet known. He emphasized the importance of
continuing to evaluate both products during the upcoming RSV season.
Dr. Levi requested clarification to ensure his understanding was accurate. He inquired whether
there is currently an ongoing trial for clesrovimab in which the most recent reporting shows eight
deaths in the immunized group compared to four deaths in the non- immunized group receiving
standard care. He asked if that was an accurate interpretation of the available data.
A representative from Merck confirmed that, in addition to the healthy infant study (Protocol 4, also known as CLEVER), there is an ongoing trial in at -risk infants called Protocol 7, also
referred to as SMART. In this study, infants are randomized one -to-one to receive either
clesrovimab or palivizumab. An interim analysis was conducted to support FDA licensure, and
as noted, it showed eight deaths in the clesrovimab arm and four in the palivizumab arm. Each of these deaths was thoroughly evaluated and rev iewed by an independent external data
monitoring committee. As with the earlier trial, no deaths were attributed to the study
intervention. There was no evidence of clustering by cause, system organ class, or timing of the
events. The representative emphas ized that these events are rare and that the study remains
ongoing.
Dr. Meissner stated that these issues were thoroughly discussed within the workgroup, which
included over 60 members. He emphasized that the group carefully reviewed all available data
in detail and appreciated Dr. Levi's close examination of the records. However, he noted that the workgroup was comfortable with the findings from the clesrovimab trials. He acknowledged that
studies involving high- risk infants, including those born preterm, involve a particularly fragile
population where unexpected deaths can unfortunately occur in both treatment and control
groups. Dr. Meissner reiterated that there was no evidence of an imbalance or pattern in serious adverse events among clesrovimab recipients. He concluded by affirming the workgroup’s
confidence in the recommendation they made.
Dr. Kulldorff expressed his gratitude to the work group, noting that the effort involved not only Dr. Meissner but many others who worked very hard on this review. He also thanked his fellow
ACIP committee members, noting that while the presentations from the previous day primarily
focused on the maternal vaccine and nirsevimab, which had already been recommended in a prior meeting, the work group members went beyond that information. They examined the data
on clesrovimab in great detail, which is the produ ct currently under consideration and was
recently approved by the FDA. He commended the committee for stepping in and conducting a
very thorough review.
Dr. Malone stated that there has been very active discussion and consideration within the
committee regarding this product. For the record, he emphasized that the topic has been
thoroughly debated internally. Despite the short timeframe available to addres s it, he expressed
confidence that the committee had sufficient information. He noted that the committee had
rigorously considered the various aspects of the product, had been appropriately briefed on the
underlying issues and science, and had taken the ti me to investigate and discuss the matter to
the best of its ability.
46
 Dr. Hopkins, representing the National Foundation for Infectious Diseases, emphasized that
RSV is the leading cause of hospitalizations in infants in the United States. He stated that the
scientific evidence clearly supports the use of maternal RSV vaccines during pregnancy, as well
as monoclonal antibodies for infants whose mothers were not vaccinated. He urged ACIP to ensure that any changes to RSV recommendations remain grounded in evidence. He reaffirmed
NFID’s commitment to protecting infants from seri ous RSV -related outcomes.
Dr. Levi shared a personal perspective, noting that while he is a scientist, he is also a father of
six children. He emphasized the importance of considering the parents' viewpoint when
evaluating the data. Reflecting on his own experience, he explained that if he were the parent of
a baby born prematurely or with underlying health conditions, he would likely choose to use
these products, given the serious threat RSV can pose to vulnerable infants. However, he stated that if his child were healthy and born full- term, he would feel hesitant about using a new
product, even with scientific knowledge in hand. He expressed concern about introducing an
immunization for a disease that has historically presented challenges in vaccine development.
Dr. Levi emphasized that, beyond metrics such as hospitalization and disease burden, it is
crucial to consider how parents might perceive and respond to the available data. He concluded
by acknowledging that, as a father, he would feel cautious in such a situation and wanted to
share that perspective with the committee.
Dr. Pepsworth asked for clarification on the differences in health outcomes between very sick
infants and healthy children. She also inquired about available data on the effectiveness and
safety of clesrovimab when administered according to the current imm unization schedule.
Specifically, she questioned whether there is information on the safety of administering
clesrovimab concurrently with other routine vaccines, including those for hepatitis B, rotavirus,
DTaP, Hib, pneumococcal, polio, COVID -19, and inf luenza. She emphasized the importance of
understanding how simultaneous administration may impact safety outcomes.
Dr. Meissner responded by explaining that approximately 80% of children hospitalized for RSV are otherwise healthy, without prematurity, congenital heart disease, or chronic lung disease.
These infants typically become symptomatic when infected, and about one -third of RSV cases
in children lead to lower respiratory tract infections that require medical attention, such as visits to a pediatrician or the emergency department, even if hospitalization is not required. He
emphasized that it is currently not poss ible to predict which healthy infants will develop severe
disease, making it difficult to target monoclonal antibody use solely based on known risk factors.
While RSV -related deaths in infants are very rare in the United States, with fewer than 100
annuall y and mostly among those with comorbidities, hospitalization is the most reliable primary
endpoint to assess product effectiveness, with ICU admissions also being monitored. He
clarified that products like clesrovimab and nirsevimab are monoclonal antibodi es administered
passively and are not vaccines in the traditional sense, as they do not stimulate an immune
response. He addressed maternal vaccination, stating that if a pregnant woman chooses not to
receive an RSV vaccine between 32 and 36 weeks of gestation, the alternative is to administer a monoclonal antibody to the infant at birth. He added that if he were Dr. Levi’s pediatrician, he
would strongly recommend that his wife either receive the maternal RSV vaccine or that the
newborn receive a monoclonal antibody. He expressed strong support for the progress made in
47
 RSV prevention, crediting much of it to the work of Barney Graham, who received NIH support.
He described the new monoclonal antibody products and vaccines as remarkable, both safe
and effective. He stated that the work group and the FDA had conducted extensive reviews,
leaving no unresolved safety or efficacy issues in his view.
Dr. Kulldorff addressed Dr. Pebsworth’s question about the concomitant administration of
monoclonal antibodies with routine childhood vaccines given on the same day. He noted that the work group had reviewed this issue and requested follow -up from Dr. Meis sner to provide
additional context and information.
Dr. Meissner explained that there are three monoclonal antibodies used for the prevention of
RSV. Palivizumab was the first -generation product, introduced around 1999, while clesrovimab
and nirsevimab are second- generation antibodies that incorporate speci fic mutations in the Fc
fragment, extending their half -lives. This allows a single dose to protect throughout the RSV
season. In contrast, palivizumab required monthly dosing for five months to maintain coverage
during the season. He noted that there is ex tensive experience with palivizumab, and despite its
repeated dosing schedule, no interference has been observed with any of the standard,
routinely recommended childhood vaccines. Based on this experience, he expressed
confidence that concomitant administ ration with other vaccines is not a concern.
Dr. Goldman, representing the American College of Physicians and speaking as an individual,
expressed support for the intervention under consideration. He thanked Dr. Meissner for his earlier remarks and added that, as a clinician, he sees firsthand the im pact of diseases when
they are not prevented or treated. He emphasized that healthy children do get RSV, and some become seriously ill, are hospitalized, or even die. He cautioned against limiting interventions only to those identified as high- risk, since risk is often not fully understood until illness occurs.
He noted that this product is not a vaccine but rather provides passive immunity. As a father of
two children, he wished it had been available when they were born. He called the product a major advancement in medical science and urged the committee to approve the resolution to
help protect children and keep them healthy.
Dr. Meyer addressed Dr. Pepsworth’s earlier question about the co -administration of monoclonal
antibodies with other vaccines. She noted that real -world evidence from the Vaccine Safety
Datalink, presented by Dr. Daly the previous day, showed that a high proportion of infants had
received clesrovimab at the same time as another routine vaccine. She then turned the
discussion over to Dr. Daly to provide further details from the real -world data.
Dr. Daley explained that the safety data presented the previous day covered approximately 74,000 infants who received nirsevimab, making the dataset roughly 20 times larger than the
original clinical trial. This data reflects real -world use in routine prac tice. He highlighted that
among the neonate cohort, 20 percent received same- day hepatitis B vaccination, and among
the older infant group, 84 percent received same -day vaccination with routine childhood
vaccines. He concluded that the safety evidence, par ticularly for infants aged 37 days to less
than 8 months, does include and support safety with simultaneous vaccination.
Dr. Malone shared a concern raised by colleagues in the medical community, particularly among primary care providers, about the possibility that monoclonal antibody products may simply
48
 delay RSV infection from the first year of life to the second. He noted that Dr. Meissner had
previously discussed the current understanding of RSV pathophysiology and asked him to address this issue. Specifically, he requested that Dr. Meissner explain the role of terminal micro airway development in infants and how it relates to the effectiveness and implications of
administering this product during early infancy.
Dr. Meissner explained that the most severe RSV disease typically occurs in the first 90 days of
life, as this is when infants are at the highest risk of hospitalization. The increased risk is due to the small size of their bronchioles, which are the narrow airways that conduct air into the alveoli, the tiny air sacs in the lungs where oxygen and carbon dioxide are exchanged. In very young or
preterm infants, these small airways can become completely blocked by inflammation during an
RSV lower respiratory tract infection. By the second year of life, a child’s airways are larger, making it much less likely that a small amount of inflammation will cause significant respiratory distress. Monoclonal antibodies are given to healthy infants to prevent RSV infection during the highest -risk period, particularly the first 90 days. Dr. Meissner noted that these antibodies do not
fully prevent infection but instead reduce the likelihood of lower respiratory tract disease, allowing the child to build natural immunity. This may offer protection in the second year of life. Even if infection shifts to the second year, it is generally less problematic because the airways
are larger and better able to tolerate inflammation without becoming obstructed.
Dr. Meissner recognized the contributions of Jefferson Jones, who led the work group throughout the process and was praised for doing an exemplary job.
Dr. Levi encouraged CDC colleagues to expand post -marketing analyses to include data on
deaths and a broader range of potential adverse events. He emphasized the importance of
understanding the risks alongside the benefits, regardless of the decision to use the product. He emphasized the importance of transparency in assessing the trade- offs involved. While he
acknowledged that the analysis presented the previous day was very well done, he noted that it was limited in scope, focusing only on specific periods and certain adverse events, and
expressed hope that future analyses would be more comprehensive.
Dr. Kulldorff expressed his deep appreciation to the work group for their thorough efforts, to the
CDC staff for their support, and especially to his fellow committee members. He acknowledged that, despite very short notice, the group fully engaged with the review of clesrovimab, which
was only approved by the FDA 16 days prior. He recognized the challenge of gathering and
reviewing a large amount of information in a limited timeframe and thanked everyone for their
commitment to carefully evaluating all the available data.
Vote: RSV Maternal/Pediatric Vote

Dr. Martin Kulldorff (ACIP Chair) read the following proposed ACIP voting language for the
RSV Maternal/Pediatric vaccine into the record:

A
CIP recommends infants aged <8 months born during or entering their ﬁrst RSV
season who are not protected by maternal vaccination receive one dose of
clesrovimab.
49

Motion/Vote: RSV Vaccines

Dr. Malone motioned to approve the recommended voting language, stating, ”ACIP
recommends infants aged <8 months born during or entering their ﬁrst RSV season who are
not protected by maternal vaccination receive one dose of clesrovimab. ” Dr. Pagano
secon ded the motion. No COIs were declared. The motion carried with 5 in favor and 2
opposed. The disposition of the vote was as follows:

   5 Favored:  Malone, Hibbleln, Pagano, Meissner, Kulldorff
    2 Opposed:   Levi, Pebsworth
    0 Abstained:

Vote:
 RSV Maternal/Pediatric- VFC Vote

Dr. Martin Kulldorff (ACIP Chair) read the following proposed ACIP VFC vote for RSV
Maternal/Pediatric into the record:

A
pprove the updated Vaccines for Children (VFC) resolution for prevention of RSV .

Motion/Vote: RSV Vaccines

Dr. Malone motioned to approve the recommended updated Vaccines for Children (VFC)
resolution for prevention of RSV . Dr. Pagano seconded the motion. No COIs were declared.
The motion carried with 15 in favor and 0 opposed. The disposition of the vote was as
follows:

    7 Favored:  Malone, Hibbleln, Pagano, Levi, Meissner, Pebsworth, Kulldorff
    0 Opposed:
    0 Abstained:

*Dr. Pebsworth disclosed that she owns shares in a healthcare sector fund that includes holdings relevant
to ACIP discussions, including vaccine manufacturers. However, the value of these holdings falls below
the de minimis threshold set by the Office of Government Ethics. Based on this, she confirmed her understanding that she is permitted to participate in the ACIP meeting fully.

PUBLIC C OMMENT

The f
loor was opened for public comment on June 25, 2025. The comments made during the
meeting are summarized in this document. Members of the public were also invited to submit
written public comments to ACIP through the Federal eRulemaking Portal under Docket Number
ID CDC- 2025- 0024. Visit regulations.gov  for access to read the comments received.
50
 Kim Mack Rosenberg, Esq.
Children’s Health Defense and Mack Rosenberg Law LLC

A
 representative from Children’s Health Defense provided public comment expressing concern
over the misuse of ACIP’s best practice guidelines by several states, including California and
New York, to restrict medical exemptions for school vaccine requiremen ts. The commenter
noted that ACIP guidelines define contraindications and precautions broadly, recognizing that
the lists are not exhaustive and cannot account for every circumstance in which a child may
need a medical exemption. However, many states and school districts are limiting exemptions to
only those explicitly listed, or even further restricting them to cases of anaphylaxis, disregarding
other serious medical risks identified by treating physicians. The speaker urged ACIP to amend its best practices guidelines or issue a public statement clarifying that the CDC is not authorized
to provide individualized medical advice and that clinical decisions regarding exemptions should
be made by treating physicians using CDC guidance, medical history, and clinical judgment. The
commenter shared the case of a 16 -year-old student in New York with multiple health
conditions, including acquired von Willebrand’s disease and a history of severe vaccine reactions. Despite certifications from six licensed physicians stating that a third hepatitis B
vaccine dose could endanger her life, her school district denied the exemption because her conditions are not explicitly listed as contraindications by ACIP. The commenter emphasized
that similar cases occur frequently, and some children have suffered serious injuries after being
forced to vaccinate against medical advice. The speaker concluded by urging ACIP to act
promptly to clarify its guidelines and protect both vulnerable students and physician autonomy.
Chrissie Juliano, MPP
Big Cities Health Coalition

C
hrissie Juliano, Executive Director of the Big Cities Health Coalition (BCHC), provided public
comment expressing concern over Secretary Kennedy’s recent dismissal of all 17 prior ACIP
members, including Dr. Mysheika Roberts, Columbus Health Commissioner and BCHC board member, who was scheduled to join the committee. Juliano emphasized the critical role of local
health departments in vaccination efforts and the trusted relationships they build with
communities. She stressed that ACIP’s independent, science- based vaccine recommendations
have guided public health for over 60 years, and sudden leadership changes risk increasing confusion and public distrust at a time when vaccine confidence is already fragile. She highlighted the resurgence of vaccine- preventa ble diseases, such as measles, and underscored
the importance of maintaining equitable access to routine vaccines. Juliano urged the new committee members to continue ACIP’s tradition of making decisions based on science and
evidence to protect public health.

D
r. Mary Koslap -Petraco
Pediatric Nurse Practitioner House Calls

Dr
. Mary Koslap -Petraco, a pediatric nurse practitioner with over 30 years of experience,
provided public comment expressing concern about the recent dismissal of 17 ACIP members. She stated that the former members had the expertise to design vaccine studi es and voiced
concern that the current committee has misinterpreted VAERS data, which provides safety
signals but does not establish causality. Dr. Koslap- Petraco emphasized the need to keep
COVID -19 vaccines available for children who need them, noting that misinformation has led
parents to lose trust in healthcare providers. She shared personal experiences with vaccine-
preventable diseases in her own family. She warned that if access to vaccines is reduced, more
children will suffer and die from diseases that are currently preventable. As a Vaccines for
51
 Children (VFC) provider, she urged ACIP to continue ensuring that all children have access to
life-saving vaccines.

M
arcia Cohen Zakai
Private Citizen

M
arcia Cohen Zakai provided public comments, questioning the recent dismissal of all 17 ACIP
members and calling the action unjustified, while raising concerns about its impact on public trust. She referenced a letter from the California Medical Association, the American Medical
Association, and over 100 other medical organizations urging the reinstatement of the
dismissed members. Zakai stressed that ACIP’s evidence- based recommendations have
historically ensured access to FDA -approved vaccines through a transparent process, and that
the current vacancies risk creating confusion and undermining vaccine confidence. She warned that this could lead to preventable illness, disability, and death. Zakai emphasized the urgent
need for expert vaccine guidance, especially amid ongoing COVID -19 and measles outbreaks,
to protect the public and maintain widespread access to life- saving vaccines.

C
aroline Brown, MD
The Children’s Clinic of Winston Salem

D
r. Caroline Brown, a general pediatrician from North Carolina, provided public comment
expressing deep concern about declining vaccination rates and the resurgence of vaccine-
preventable diseases. Drawing from nearly two decades of clinical experience, she described firsthand encounters with severe illness in children, including cases of RSV, pertussis, and
complications from diseases now preventable by vaccines. She noted that when she trained in
the early 2000s, routine spinal taps were performed on febr ile infants to rule out meningitis. Still,
vaccines like Hib and pneumococcal conjugate have since spared many children from such procedures and outcomes. Dr. Brown reported that just one day before the meeting, the first confirmed case of measles was announced in her county. She has since been responding to
concerned parents in her community. She emphasized that measles was eradicated in the
United States 25 years ago. Still, its return is a direct result of declining vaccine uptake driven
by misinformatio n, some of which she stated is amplified by members of the committee itself.

D
r. Alexandra Jones Packham
Private Citizen

D
r. Alexandra Jones Packham, a recent medical school graduate and incoming resident in
internal medicine and pediatrics, provided public comment. She shared that she is currently
pregnant and due in the middle of respiratory season, giving her a unique perspective as both a
future pediatrician and a soon- to-be mother. Reflecting on her medical training, she described
her experience in the pediatric ICU during the winter, where she saw numerous cases of bronchiolitis caused by RSV and influenza. She emphasized the limited treatment options for
these infections, noting that supportive care is often the only intervention available while the
body fights off the virus. Dr. Packham observed that during her rotations, every child she saw hospitalized with a severe respiratory infection had not been vaccinated against the pathogen
involved, either due to parental choice or because they were too young to qualify for
vaccination. She highlighted the effectiveness of vaccines and RSV monoclonal antibodies in
preventing severe illness and stated her intention to receive the RSV, flu, and COVID -19
vaccines during her pregnancy. She also plans to ensure her child gets all recommended
vaccines and antibody protections when eligible. Dr. Packham concluded by stressing the
52
 importance of providing parents with the opportunity to discuss vaccination with their
pediatricians and that vaccines and antibodies remain accessible and covered by insurance.

Di
ana Figueroa, LVN
Kaiser Permanente

Di
ana Figueroa, a licensed vocational nurse (LVN) with 16 years of experience, including 14
years in pediatric care, provided public comment. She expressed concern over the recent termination of 17 ACIP members, describing it as a poor decision given their  extensive vetting
and history of making evidence- based vaccine recommendations. She stated that the removal
of these members undermines trust in the vaccine decision- making process and increases the
risk of health policy being influenced by unqualified individuals making decisions based on
personal opinions rather than scientific evidence. Ms. Figueroa also addressed shared clinical
decision- making, noting that it creates barriers for LVNs and LPNs like herself to administer
requested vaccines, ultimately delaying patient care. She emphasized that the healthcare system is already overwhelmed and that preventative care, including immunizations, is critical to
reducing costly hospitalizations for both chronic and infectious diseases. She urged the FDA
and CDC  not to create additional barriers to vaccine access. She emphasized the importance of
protecting vulnerable populations, including pregnant women, newborns, the
immunocompromised, the elderly, and healthy individuals who choose to be vaccinated to
protect  their communities. Ms. Figueroa called for the reinstatement of the previously terminated
ACIP members, the removal of recently appointed unvetted members, and the restoration of prior COVID -19 vaccine recommendations for pediatric and pregnant populations, which she
believes have been effective in preventing disease.

Dr
. Amy Hardin
Northside Pediatrics

D
r. Amy Hardin, a pediatrician in private practice in Woodstock, Georgia, provided public
comment emphasizing the critical importance of vaccines in preventing severe childhood illnesses and deaths. She reflected on her training at Emory from 1990 to 1993,  when, before
the introduction of Haemophilus influenzae type B (Hib) and pneumococcal vaccines, pediatricians frequently admitted children with high fevers for complete septic workups. These included blood cultures, catheterized urine samples, and spinal taps to check for meningitis and
sepsis. At that time, one in 200 children under five developed invasive Hib disease, resulting in
conditions such as sepsis, epiglottitis, cellulitis, and meningitis. Many children died, while others
were left with lifelong  disabilities, including deafness, cerebral palsy, and severe learning
challenges. Dr. Hardin noted that she has not seen a single case of Hib or pneumococcal
meningitis or sepsis since 1999, a year she remembers vividly because it was the last time she
attended a funeral for a child who died from a vaccine- preventable disease. She recounted the
death of a two -year-old boy who missed his routine vaccination and died from pneumococcal
infection three months later. She expressed concern that vaccine hesitancy  and misinformation
are causing a resurgence of vaccine- preventable diseases. Her colleagues in Atlanta are now
treating new cases of Hib meningitis, primarily in unvaccinated children whose parents were
influenced by misinformation online. Dr. Hardin urged ACIP members to protect the health of America’s children by continuing to promote evidence- based vaccine policies. She concluded by
affirming that vaccines are safe, effective, and lifesaving, and warned against allowing the country to return to a time when preventable childhood deaths and disabilities were common.

A
drianna Williams
Private Citizen
53

Adr
ianna Williams, a private citizen, provided public comment expressing strong opposition to
vaccines, including those under discussion at the meeting. She referenced the Hippocratic Oath
and stated her belief that vaccines cause harm and should be abolis hed. Ms. Williams asserted
that there are safer, natural alternatives for disease prevention. She described vaccines as a bioweapon mechanism, claiming that cumulative harm results from the interaction of vaccine ingredients with bodily systems. She cited data from the Vaccine Adverse Event Reporting
System (VAERS), reporting over 8,000 adverse events and more than 70 deaths following RSV
vaccination. She specifically referenced VAERS report ID 28021 as an example of an RSV
vaccine- related death. Ms. Williams urged ACIP members to listen to individuals who report
vaccine injuries and called for the immediate cessation of all vaccine recommendations,
beginning with the RSV vaccines under consideration at this meeting. She concluded by asking
the committee to act following the principle of "do no harm" and to prioritize the health and
safety of both present and future generations.

Rosel
ie Bright, ScD
Private Citizen

Dr
. Roselie Bright, a retired epidemiologist from the FDA, expressed concern about the recent
erosion of scientific integrity in federal health agencies. She described how, during her career, regulatory decisions were based on transparent documentation and  collaboration among
experts, which built trust in the process. However, she now questions federal decisions due to political interference, mass firings of scientists, and changes to the structures of advisory committees. Bright urged continued consideration of long COVID in vaccine recommendations,
universal access to COVID -19 vaccines three times per year, and the development of more
effective vaccines. She called for increased transparency in ACIP meetings, including simultaneous public access to meeting materials, more time for public comment, and
summaries of those comments during meetings. She also advocated reinstating the 17 removed
ACIP members, requiring scientific competency for all members, and barring anyone who
disregards research ethics from serving in advisory roles.
Due to time constraints, Dr. Kulldorff announced that the remaining RSV discussion will continue on July 26, 2025; summaries of those discussions are included in the RSV section
above. The meeting was then recessed until July 26, 2025, at 8:00 AM  EST.

THURSDAY : APRIL  26, 2025

WELCOME AND I NTRODUCTIONS

C
all to Order/Roll Call

D
r. Martin Kulldorff, Chair of the ACIP, convened the meeting on June 26, 2025. Dr. Mina
Zadeh, ACIP Executive Secretary from the CDC, welcomed the committee, followed by a roll call from members, each of whom announced their presence.

INFLUENZA  VACCINES

D
r. Vivien Dugan (CDC/NCIRD) summarized the influenza vaccine session, which covered five
presentations. These included data on the immunogenicity and safety of the Flublok
54
 recombinant influenza vaccine in older children and adolescents, updated estimates of influenza
burden and the impact of influenza vaccination for the 2024– 2025 influenza season, an
overview of the 2024– 2025 influenza season with proposed influenza vaccine recommendations
for 2025– 2026, a review of thimerosal preservative and proposed updates related to the use of
thimerosal -containing influenza vaccines.
Dr. Pedro Folegatti (Sanofi Pasteur) presented the results of a Phase 3 immunobridging non -
inferiority trial evaluating the quadrivalent recombinant influenza vaccine (RIV4) , which is
licensed as Flublok in older children and adolescents, compared to adults. Dr. Folegatti
disclosed that he was a full -time employee of Sanofi and held shares in the company.
Recombinant protein technology has been established a proven approach to vaccine development against infectious diseases since the late 1980s, demonstrating safety and
effectiveness across multiple pathogens, including hepatitis B, HPV, zoster, COVID -19, and
influenza. For influenza vaccines, this technology offers several advantages: it maintains the
sequence integrity of flu antigens consistent with FDA -selected strains, operates independently
of egg supply, and does not involve culturing or handling live influenza viruses. As a result, there
is no egg adaptation of the virus. Additionally, the recombinant influenza vaccine avoids the
inactivation step, preserving the native hemagglutinin conformation of the wild- type virus, which
supports a more optimal protective immune response.
Key clinical evidence supporting Flublok includes several Phase 3 trials. In a randomized controlled efficacy trial among adults aged 50 and older, Flublok provided 30 to 43% greater
protection against biologically confirmed symptomatic influenza compared to a U.S. -licensed
standard -dose inactivated influenza vaccine during a predominantly H3N2 mismatch season. A
Phase 3 immunobridging study in adults aged 18 to 49 demonstrated non -inferior immune
responses to three of four strains when compared to the same standard -dose vaccine. The
trivalent formulation of Flublok was first licensed in 2013, followed by the quadrivalent version in 2016 for individuals aged 18 and older. The label has since been updated and approved by the
FDA to include children aged 9 and  older, based on the data presented today. As of January 31,
2025, more than 43 million doses of Flublok have been distributed globally. The vaccine has an
established safety profile and is well tolerated, with no safety signals identified to date.
The study presented was part of a pediatric research plan for Flublok, developed in coordination with the FDA and international regulatory authorities. It was a Phase 3, multi -center, open- label,
non-randomized immunobridging study conducted at 36 sites ac ross Spain, Poland, the Czech
Republic, and the U.S. The trial aimed to enroll up to 1,334 healthy participants aged 9 to 49 years, all of whom received a single dose of Flublok. The primary objective was to demonstrate
non-inferiority of immune responses in children and adolescents (ages 9– 17) compared to
adults, where vaccine efficacy had already been established. Immune responses were evaluated using hemagglutination inhibition antibody titers and seroconversion rates four weeks
post-vaccination. The key  secondary objective was to assess the safety profile of Flublok by age
group.
Participants received their vaccination on Day 1, with a baseline blood sample collected. This
was followed by a safety phone call on Day 9 and a clinic visit on Day 29 for a safety review and
a second blood draw. They were monitored for six months after v accination. Solicited local and
systemic adverse events were collected over a seven- day period, while unsolicited and
medically attended events were tracked for 28 days. Serious adverse events and adverse
events of special interest were monitored throughout the study. Key exclusion criteria included
receipt of any vaccine within four weeks before or after enrollment, except for COVID -19
vaccines, which were allowed if administered at least two weeks apart from the study vaccine, and receipt of any influenza vaccine within the six months before enrollment. The primary
55
 immunogenicity endpoints were geometric mean titer (GMT) ratios and seroconversion rates at
Day 29 for each of the four influenza strains. The study was designed with 80% power to
demonstrate non- inferiority based on eight tests. Non- inferiority was met if  the lower bound of
the 95% confidence interval for GMT ratios was greater than 0.667, and the lower bound for the
difference in seroconversion rates was greater than - 10%.
Of the 1,334 participants initially planned, 1,308 were enrolled between October 27, 2022, and
May 1, 2023. A total of 641 participants in the 9 to 17- year-old group and 658 participants in the
18 to 49- year-old group received the vaccine. Among them, 626 children and adolescents, as
well as 634 adults, provided both pre - and post -vaccination blood samples for the primary
endpoint. Overall, the study achieved high and comparable retention rates across both age
groups.
The study included more females than males. The mean age was 13 years in the 9 to 17- year-
old group and 34 years in the 18 to 49 -year-old group. Most participants were White, with Black
or African American individuals making up nearly 19% of the total enrolled population.
Additionally, 87% of participants identified as non -Hispanic or Latino.
The primary endpoint assessed antibody responses four weeks after vaccination, comparing the
9 to 17- year-old group with the 18 to 49- year-old group. Geometric mean titers (GMTs) on Day
29 were evaluated for all four influenza strains in the vaccine. The data showed that antibody
responses were comparable between the two groups, with children and adolescents generally
exhibiting higher responses than adults. The GMT ratios, along with their 95% confidence
intervals, all exceeded the non- inferiority margin o f 0.667. The lower bounds ranged from 1.09
for B/Yamagata to 2.76 for H3N2, demonstrating that non- inferiority was met for all strains.
Seroconversion was defined as a four -fold or greater increase in antibody titers for participants
with a baseline hemagglutination inhibition (HAI) titer of 10 or higher, or a post -vaccination titer
of at least 40 for those who were seronegative at baseline. The differences in seroconversion
rates between the 9-  to 17 -year-old group and the 18-  to 49 -year-old group ranged from ( -)
0.59% for H3N2 to 14.3% for B/Yamagata. In all cases, the lower bound of the 95% confidence interval remained above the non -inferiority margin of –10%, indicating that the primary objective
of demonstrating non- inferior immune responses was achieved for all four influenza strains,
based on both Day 29 geometric mean titer ratios and seroconversion rates.
For the secondary objective, 10 participants, representing less than 1% of the total enrolled
population, reported at least one serious adverse event, and 5.1% reported at least one
medically attended adverse event. None of these events w
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Summary: MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)     J UNE 25-26 , 2025  MEETING SUMMARY                                                                        Tr ade names are used for identification purposes only and do not indicate endorsement.          2   WEDNESDAY : JUNE  25, 2025    WELCOME AND I NTRODUCTIONS     C all to Order/Roll Call     D r. Martin Kulldorff, Chair of the ACIP, convened the meeting on June 25, 2025. He welcomed  the members, thanked the current…