summary 2025 9 18 19 508

MEETING OF THE ADVISORY
COMMITTEE ON IMMUNIZATION
PRACTICES (ACIP)

SEPTEMBER  18-19, 2025
MEETING SUMMARY

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

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Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  THURSDAY : SEPTEMBER 18, 202 5

WELCOME AND ROLL CALL

Call to Order/Roll Call

Dr. Mina Zadeh, ACIP Executive Secretary, CDC, convened the meeting at 10:00 a.m. on
September 18, 2025, and welcomed participants to the September 18– 19 session of the
Advisory Committee on Immunization Practices (ACIP). She provided general logistical information and noted that presentation slides were available on the ACIP website. Dr. Zadeh
reviewed the public comment process, explaining that two oral comment sessions were
scheduled, with 19 speakers selected in advance through a blinded lottery, and that written
comments were accepted through regulations.gov (Docket No. CDC -2025 -0454). She
reaffirmed ACIP’s commitment to transparency and reviewed conflict of interest policies, noting that members must disclose relevant conflicts and may receive limited waivers for activities that
enhance expertise but may not vote on related matters.

Dr. Zadeh then conducted the roll call and introduced five new ACIP members appointed for the September 2025 meeting: Dr. Catherine M. Stein, Dr. Evelyn Griffin, Dr. Hilary Blackburn, Dr.
Kirk Milhoan, and Dr. Raymond Pollak. A complete list of Members, Ex  Officio members, and
Liaison Representatives is provided in the appendices at the end of this summary document.
While no conflicts of interest were identified for the first day of the meeting, Dr. Robert Malone
abstained from the MMRV votes due to existing legal agreements.

UPDATE ON WORK GROUPS

Dr. Kulldorff provided an update on the  current  work group s, noting that several are actively
engaged in ongoing scientific discussions and analyses, with some scheduled to present their
deliberations during this session. He announced the formation of two new work groups: one
focused on vaccines in pregnant women  and another on the childhood and adolescent vaccine
schedule.

He explained that most existing work groups focus on individual vaccines or related vaccine groups . The new group will  examine interaction effects and optimal sequencing within the
broader vaccine schedule. Dr. Kulldorff emphasized the importance of careful consideration when evaluating vaccines during pregnancy due to potential risks, such as birth defects. He
concluded by noting that findings from these new work groups will be presented at future ACIP
meetings.

MEASLES, MUMPS, RUBELLA, AND VARICELLA  (MMRV) VACCINE

Introduction
Dr. Martin Kulldorff (ACIP Chair)
Dr. Martin Kulldorff, Chair of the ACIP, opened the session by introducing the MMRV (measles, mumps, rubella, varicella) vaccine. He noted that the vaccine combines protection against four
diseases in a single injection, developed to replace two separate shots (MMR and varicella),
thereby reducing the number of needles children receive.

3
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Background on MMRV
Dr. Arjun Srinivasan (CDC/NCIRD)
Dr. Arjun Srinivasan (CDC/NCIRD) provided background information on the measles, mumps,
rubella, and varicella (MMRV) vaccine. He reviewed the significant health burden of these
diseases in the United States (U.S.) before vaccine introduction. During the 1964 to 1965
rubella epidemic, approximately 11,000 pregnant women lost their babies, 2,100 newborns died,
and 20,000 were born with congenital rubella syndrome, which can cause deafness, heart
defects, and developmental delays. Before the measles vaccine, an estimated 48,000
hospitalizations and 400 to 500 deaths occurred each year due to measles. Mumps was the
leading cause of viral encephalitis and sudden -onset deafness before the introduction of
vaccination. In the early 1990s, varicella caused between 10,500 and 13,500 hospitalizations
annually, along with 100 to 150 deaths.
 The introduction of vaccines to protect against these diseases, in the form of monovalent
vaccines and combination vaccines such as MMR (measles, mumps, rubella) and MMRV
(measles, mumps, rubella, varicella), coupled with achieving and maintaining coverage  rates
above 90%, led to dramatic reductions in disease burden in the U.S. These efforts resulted in the elimination of endemic measles in 2000, elimination of endemic rubella in 2004, a 99%
decline in mump cases by the early 2000s, and a 97% decline in va ricella incidence by 2019.

In the U.S., two options are available for measles, mumps, rubella, and varicella vaccination: the
combination MMRV vaccine or MMR plus varicella vaccine. The routine schedule consists of
two doses, administered at 12– 15 months and 4– 6 years. The MMRV vacc ine available in the
US, ProQuad, manufactured by Merck, was licensed by the FDA in September 2005 based on
the non -inferior immunogenicity of its components compared with the simultaneous
administration of the MMR and varicella vaccines. Efficacy of the i ndividual components had
already been established in clinical studies of the monovalent vaccines. At the time of  MMRV
licensure, disease burden in the U.S. was too low to perform efficacy -based clinical trials for the
MMRV vaccine , so immunobridging trials were used to support approval.  [Of note,
immunobridging trials is an established approach for the development of vaccines. ]

Immunogenicity after the first dose of MMRV was compared with that of MMR plus varicella
vaccine in children aged 12– 23 months in four randomized clinical trials. A total of 5,446
children received MMRV and 238 received MMR plus varicella at separate injec tion sites. In
these studies, seroconversion rates and geometric mean titers were similar between groups and met the pre -established criteria for non -inferiority. Immunogenicity after the second dose in
children aged 4– 6 years was assessed in one randomized clinical trial, where 399 children
received MMRV, 205 received MMR plus placebo, and 195 received MMR plus varicella. The
findings also met the pre -established criteria for non- inferiority. As noted in the 2008 and 2009
reviews by the ACIP Vaccine Work G roup, safety after MMRV was compared with MMR plus
varicella. Based on the demonstrated non- inferior immunogenicity, vaccine effectiveness was
assumed to be equal.

Upon licensure in September 2005 for children aged 12 months t hrough  12 years, MMRV was
preferred over the separate administration of MMR and varicella vaccines, consistent with the
ACIP’s preference at the time for combination vaccines. In February 2008, preliminary post -
licensure safety findings from two studies identifi ed an increased risk of febrile seizures after the
first dose of MMRV, leading ACIP to remove its preference for MMRV over separate
administration of MMR and varicella for both the first and second doses. After further review of
safety data, consideration of the benefits of one fewer injection with MMRV, analysis of febrile
4
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  seizure epidemiology, input from parents and providers, and consultation with ethics experts,
the ACIP issued updated recommendations in June 2009.
 These recommendations remain current and state that for the first dose of measles, mumps,
rubella, and varicella vaccination at age 12– 47 months, either MMR plus varicella or MMRV
may be used. Providers who consider administering MMRV should discuss the benefits and
risks of both options with parents and caregivers. At the time of publication, CDC
implementation guidance recommended that, unless a parent or caregiver specifically preferred
MMRV, the first dose in this age group should be administered as separate MMR and varicella
vaccines. For the first dose at age 48 months or older and for the second dose at any age
through 12 years, MMRV is generally preferred over separate administration of MMR and
varicella vaccines.

No post -licensure vaccine effectiveness estimates are available for MMRV used  in the U.S., as
measles and rubella have been eliminated, and mumps and varicella remain at very low levels.
There are not enough cases or outbreaks among children in the U.S. to assess vaccine
effectiveness. However, those vaccinated with either MMRV or MMR plus varicella continue to
have very low rates of measles, mumps, rubella, and varicella. To date, CDC has received no
reports suggesting lower effectiveness of MMRV compared with the separate component
vaccines, consistent with the immunogenicity resu lts observed in clinical trials.
 In terms of utilization, MMRV accounts for 15% of first -dose measles, mumps, rubella, and
varicella vaccination among children aged 19– 35 months. In most states, the use of MMRV for
the first dose ranges from about 10% to under 20%, based on the first and third quartiles. Among children aged 4– 6 years, MMRV accounts for 75% of second- dose vaccination.
 Dr. Srinivasan concluded that the MMRV vaccine is one of two options for vaccination of U.S.
children against measles, mumps, rubella, and varicella. As ACIP assessed in 2008 and 2009,
given the balance of risks and benefits of a first dose of MMRV compared with a first dose of
MMR plus varicella, and the importance of individual values and preferences in weighing these
risks and benefits , maximizing choice remains an important ethical principle. Decisions should
be made on a case -by-case basis by providers , parents, or caregivers. The two vaccination
options, MMRV or separate injections of MMR and varicella, are considered equivalent in terms
of protection. Under current recommendations, most MMRV use in the U.S. is among children
aged 4– 6 years for the sec ond dose. Overall, vaccination for measles, mumps, rubella, and
varicella has resulted in a reduction of at least 97% in all four diseases compared to the pre -
vaccine era.

Discussion
 Dr. Milhoan requested clarification on the adjuvant content, specifically comparing the amount in
the MMRV vaccine with that of administering MMR and varicella separately, and whether the
adjuvant is similar or different between these options.
Dr. Oliver, NCIRD SME, clarified that neither the MMRV vaccine nor the separately administered MMR plus varicella vaccines contain an adjuvant.

Dr. Hibbeln  inquired about the overall risk -benefit balance, noting that the benefits were
described extensively and that febrile seizures were identified as a potential risk. He requested
an assessment of the magnitude of harm from febrile seizures and other side ef fects in relation
to the benefits at both the individual and population levels.

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Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Srinivasan stated that Dr. Su would present the risk profile in the following presentation.

Dr. Malone disclosed that, due to his prior service as an expert witness in litigation involving
vaccines, which granted him access to internal manufacturer communications under a legal
agreement, he is bound not to conduct research on or offer opinions about these products. He
clarified that he will not vote on this topic and has no opinion to provide due to the pre -existing
legal agreement.

Dr. Pebsworth requested clarification on the varicella antigen amount in the two vaccination
options: MMRV versus separate MMR plus varicella, and whether the amounts differ.

Dr. Marin, NCIRD SME, clarified that the measles, mumps, and rubella components are the
same in MMR and MMRV. The varicella component in MMRV utilizes the same virus strain as
the single- antigen varicella vaccine, but at a higher potency, approximately 3.99 log10 PFU,
compared to about 3.13 log10 PFU in the single- antigen product, or roughly sevenfold higher.
The viruses themselves are identical across products; the difference is potency.

Dr. Levi asked whether there is a biological or clinical rationale for the higher varicella antigen
amount in MMRV compared with separate administration of MMR plus varicella, and why more
is needed when included in the combination vaccine.
 Dr. Marin explained that initial manufacturer trials using the same varicella potency as the
single -antigen vaccine within MMRV produced a suboptimal immunologic response to the
varicella component. Manufacturers then tested higher varicella potencies and selected the
current formulation as the best balance of immunogenicity and adverse events. Evidence
reviewed in 2008– 2009 suggested potential interference between the measles and varicella
viruses when combined in the same vaccine, resulting in a stronger measles response (with
more fever and a measles -like rash) and a weaker varicella response than with a single- antigen
varicella vaccine. Increasing the varicella potency in MMRV was intended to achieve an immune
response comparable to that of the single- antigen varicella vaccine.

Dr. Levi asked whether there is a clearly understood biological mechanism that explains why
different vaccine formulations and combinations produce different immune responses, beyond
the outcomes observed.
 Dr. Kulldorff shared that the manufacturer will provide more information on this topic later in the
meeting.

Dr. Blackburn requested clarification on immunogenicity following the first dose of the MMR
vaccine. She noted that most children develop protective antibodies after the initial dose and
asked for the scientific basis for recommending a routine second dose. She wondered whether
the second dose primarily addresses primary vaccine failure, waning immunity, or both, and
whether antibody titers could be used to verify response after the first dose, rather than
universally administering a second dose.

Dr. Oliver stated that antibody titers are one component of the protective response and are
higher after two doses. She noted that the second dose, particularly for measles, helps identify
and protect children who did not mount a protective response to the first dose, addressing
primary vaccine failure. Two doses are recommended because this schedule has been used in
many efficacy studies and provides additional overall protection.

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Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Blackburn requested percentages.

Dr. Oliver referenced slide 15 in the presentation, which showed seropositivity rates, percent
fold rise in antibody titers, and geometric mean titers across multiple doses for ProQuad
(MMRV), with MMR plus Varivax shown at the bottom of each group as the separate- vaccine
comparator.
 Dr. Milhoan inquired whether data are available on the serologic response after the primary first
dose, noting that the presented results reflect responses after the second dose, and requested
seroconversion or seropositivity data following the first dose.

Dr. Oliver shared that the data can be found on slide 13.

Dr. Meissner emphasized that while recent attention has focused on measles vaccination,
rubella vaccination is equally critical. He noted that the last rubella pandemic in the U.S.
occurred in 1964– 1965, resulting in approximately 11,000 fetal deaths and 20,000 infants born
with congenital rubella syndrome, a severe condition associated with congenital heart disease, developmental delay, and eye problems. He added that in 1969, Dr. Stanley Plotkin and
colleagues at the Wistar Institute developed the rubella vaccine, which has been highly
effective. In recent years, the U.S. has typically seen fewer than five cases of congenital rubella annually, primarily among women born in countries without rubella vaccination programs. He
underscored the importance of ens uring every child is vaccinated against measles, mumps,
rubella, and varicella.
 Dr. Meissner thanked the chair and expressed appreciation for the participation of professional
societies focused on infectious diseases and vaccines. He stated that the American Academy of Pediatrics’ non- participation in these discussions is a mistake and expressed concern that
continued absence could diminish the Academy’s influence.
Febrile Seizures following Measles, Mumps, Rubella, and Varicella (MMRV) vaccine
Dr. John Su (CDC/NCEZID)
 Dr. John Su (CDC/NCEZID) presented on febrile seizures following Measles, Mumps, Rubella,
and Varicella (MMRV) vaccine. The ACIP chair requested that the Immunization Safety Office
present an analysis of febrile seizures following the administration of MMR V compared with the
simultaneous administration of separate MMR and varicella vaccines, with results stratified by two age groups: 1– 2 and 4 –6 years. The presentation should draw on data from randomized
clinical trials and from the Vaccine Safety Datalink (VSD) project.
 Dr. Su recapped that MMRV was licensed in the U.S. in 2005. Interim recommendations in 2008
removed the preferential recommendation for MMRV, and updated recommendations were
issued in June 2009. Between February 2008 and June 2009, the MMRV Vaccine Safety  Work
Group reviewed multiple data sources, including two post -licensure studies from Merck and
analyses from the Vaccine Safety Datalink (VSD). In brief, the 2009 updates stated that unless
a parent or caregiver prefers MMRV, the first dose for children aged 12– 47 months should be
administered as separate MMR and varicella vaccines, while MMRV remains generally
preferred for the second dose. Additional details can be found in the May 2010 issue of the
MMWR Recommendations and Reports.

Background on the MMRV vaccine and febrile seizures was provided. Combination vaccines,
like MMRV, reduce the number of injections a child receives and can improve vaccine
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Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  compliance and coverage. MMRV is licensed for children aged 12 months –12 years. The
routine schedule recommends two doses: the first at 12– 15 months of age and the second at 4–
6 years  of age . ProQuad is the MMRV product licensed for use in the U.S.

Febrile seizures are seizures that occur in children who have a fever. By age 5 years, 2– 4% of
children have had at least one. They occur primarily between 6 months and 5 years  of age, with
a peak between 14 and 18 months of age. Although distressing, most febrile seizures are short (less than 15 minutes) and resolve without complications. They most commonly accompany
fevers from routine childhood illnesses such as middle ear infections, viral upper respiratory
infections, and roseola. Still, they can occur  with any condition that causes fever, including
those that follow vaccination. A family history of febrile seizures increases risk.

Pre-licensure studies of MMRV among children aged 12– 23 months found that fever and
measles -like rash were reported significantly more often during the 0– 42 days after vaccination
in children who received a first dose of MMRV than in those who received separate first doses
of MMR and varicella at the same visit. Fever occurred in 21.5% of MMRV recipients versus
14.9% of recipients of separate MMR and varicella (risk difference 6.6%; 95% CI, 4.6% –8.5%).
Considering these findings, CDC and Merck initiated pos t-licensure studies to evaluate whether
an increased risk of febrile seizures might be associated with the first dose of MMRV.

Analyses of postvaccination intervals from a Vaccine Safety Datalink (VSD) study and a Merck -
sponsored study, conducted primarily among children aged 12– 23 months, used different
populations and methods. Yet, both found significant associations in the firs t two weeks after
vaccination. The VSD study, after medical record review, confirmed an increased risk of febrile
seizures during days 7– 10 after MMRV compared with MMR plus varicella, with an attributable
risk of 4.3 per 10,000 doses and a relative risk o f 2.0 (95% CI, 1. 4–2.9). The Merck -sponsored
study also observed an increased risk during days 5– 12 after MMRV, with an attributable risk of
1.3 per 10,000 doses administered during 0– 30 days postvaccination; the relative risk was 1.1
with a non -significant confidence interval.

An analysis of VSD outpatient visits for fever among children aged 12– 23 months from 2000 to
2008 revealed that fever visits increased after any measles -containing vaccine during days 7–
10 postvaccination, with the greatest increase following MMRV. Temporal scan statistics
identified significant clustering on days 7– 10 for all measles -containing vaccines (p < 0.001),
while no temporal clustering of fever visits was observed after varicella vaccination alone.

An analysis of the number of seizures after vaccination among children aged 12– 23 months
(2000– 2008) revealed peaks on days 7– 10 following any measles -containing vaccine, with the
highest counts occurring after MMRV vaccination. Temporal scan statistics indicated significant clustering on days 8– 10 after MMRV (relative risk 7.6; p=0.001), days 7– 10 after MMR plus
varicella given at the same visit (relative risk 4.0; p=0.001), and days 7– 11 after MMR alone
(relative risk 3.7; p=0.001). No seizure peak or significant temporal clustering was observed
after varicella vaccination alone.

A review of the biomedical literature on post -licensure febrile seizures following MMR or
varicella vaccination identified one study showing a significant increase in febrile seizures during
days 8– 14 after MMR compared with unvaccinated children, corresponding to approximately
one additional febrile seizure per 3,000– 4,000 children vaccinated. No increased risk of febrile
seizure was observed among children aged 12– 23 months after varicella vaccination during the
0–30 days postvaccination.

8
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  A 2015 systematic review and meta -analysis assessed the risk of febrile seizures following
MMRV vaccination, including studies that used Priorix Tetra (MMRV) or ProQuad (MMRV). The
analysis included both clinical trials and post -marketing observations, wit h some studies
enrolling children as young as 9 months. Clinical trial data showed no significant differences in
febrile seizure incidence between MMRV and MMR, with or without varicella, after any dose
across multiple risk windows. Additionally, concomitant administration of MMRV with other pediatric vaccines was not a significant predictor of febrile seizures. In post -marketing analyses,
an approximate twofold increase in risk of seizure or febrile seizure was observed during days
7–10 or 5– 12 after MMRV vaccination in children aged 10– 24 months.

A 2021 Cochrane review examined the use of MMRV in children, including five cohort studies,
four of which evaluated first -dose vaccination only. Overall, there was a significant increase in
febrile seizure risk among children receiving MMRV compared with s eparate MMR and varicella
during the 0– 42 days postvaccination and during days 7– 10. In brand- stratified analyses, a
cohort study of Priorix Tetra reported non- significant findings for febrile seizure risk compared
with separate MMR and varicella vaccines,  including in post hoc analyses. The four other cohort
studies, which evaluated ProQuad, showed a significantly increased risk during the 0– 42-day
and 7– 10-day postvaccination windows.

Dr. Su summarized that post -licensure studies assessed febrile seizures in children aged 12– 23
months who received a first dose of MMRV compared with children who received a first dose of MMR and varicella at the same visit. Despite differences in methods,  populations  of children,
and MMRV formulations, the findings were consistent across all studies. Studies identified an
increased risk of febrile seizures during the 1– 2 weeks after the first dose of MMRV compared
with the first dose of MMR plus varicella;  outside that period, risks were similar between the two
options.
 MMRV is licensed as a two- dose series, with the routine second dose at ages 4– 6 years. The
risk of febrile seizures is lower in children aged 4– 6 years than in those aged 12– 15 months. In
Merck pre -licensure trials, fever rates were lower after a second dose of MMRV in children aged
15–31 months than after the first dose. Among children aged 4– 6 years, fever rates were similar
after receiving a second dose of MMRV and after receiving a second dose of MMR plus varicella, both administered at the same visit.

Merck -sponsored studies among children aged 4 –6 years observed no febrile seizures in either
of the comparison arms. In a VSD post -licensure study, very few seizures were identified by
ICD-9 codes after measles -containing vaccines, with no significant diff erences during days 7 –10
or 0– 42 after MMRV, MMR plus varicella, or MMR alone. However, rates were numerically
higher after MMRV. Electronic medical record review of the four events coded as seizures, 7– 10
days after MMRV, found two afebrile seizures, one indeterminate event, and one confirmed
febrile seizure. The resulting occurrence  of febrile seizure 7– 10 days after a second dose of
MMRV was 1 per 86,750 doses (about 1.2 per 100,000), with the upper 95% confidence limit corresponding to no more than 1 per 15,570 doses (about 6.4 per 100,000). Similarly, for MMR
plus varicella given the same day, the upper 95% confidence limit corresponded to no more
than one febrile seizure per 18,282 doses.
 The systematic review published in 2015 examined febrile seizure incidence and risk after the
second MMRV dose. Pre -licensure data showed no statistically significant differences between
children who received MMRV alone and those who received MMRV with one or more other
pediatric vaccines at the same visit. Likewise, there were no significant differences between children who received MMRV plus other pediatric vaccines and those who received other
9
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  pediatric vaccines without MMRV. The systematic review also summarized a post -licensure
VSD study concluding that, among children aged 4– 6 years, neither MMRV nor same -day
separate MMR and varicella vaccination was associated with an increased risk of febr ile
seizures.

Dr. Su summarized that among children aged 4– 6 years, the data do not suggest an increased
risk of febrile seizures after a second dose of MMRV compared with a second dose of MMR
plus varicella given at the same visit. In conclusion, there is a small increased risk of febrile
seizures after the first dose of measles -containing vaccines (MMR and MMRV), with the risk
slightly higher after MMRV. Studies have shown a small increased risk during days 5– 12 after
the first MMR dose; no increased risk has been observed after the varicella vaccine alone.
There is no increased risk of febrile seizures after MMRV in children aged 4– 6 years.

Discussion

Dr. Kulldorff asked whether vaccine coverage rates are influenced more by the reduced number
of injections with combination vaccines or by concerns arising from adverse reactions that may
spread through families and communities. He requested studies that quantify both effects and
indicate which has the greater impact on coverage.
 Dr. Srinivasan acknowledged the question, noted that subject matter experts could better
address the effects of vaccine coverage, and requested the backup slide on the parent and
provider survey to inform the discussion.

Dr. Oliver reported that the National Immunization Survey Child COVID module, published in
2024, asked parents to consider routine childhood vaccines (measles, polio, tetanus) and
indicate overall hesitancy. Only 14% of parents of children aged 6 months –4 years expressed
hesitancy toward these routine vaccines.
 Dr. Kulldorff asked whether the 14% hesitancy figure referred specifically to parents whose child
had experienced a febrile seizure or to the broader survey population.

Dr. Oliver clarified that the 2024 National Immunization Survey Child COVID module was a
random -digit-dial survey of the general parent population, not specifically parents of children
who had experienced febrile seizures.

Dr. Kulldorff asked how a febrile seizure attributed to MMRV, compared with MMR plus
varicella, affects parents’ willingness to continue vaccinating the child, vaccinate younger
siblings, and recommend vaccination within their social circles. He asked whet her such events
reduce coverage and whether any studies quantify these effects relative to the coverage gains from fewer injections with combination vaccines, and which effect is larger.

Dr. Oliver referenced background slide 27 from the MMRV presentation and noted that there are
no survey data specifically of parents whose children previously had febrile seizures. She
explained that during the 2008– 2009 Work Group discussions, a parent su rvey of mothers
found that approximately 33% would be resistant to MMRV, about 25% were neutral, and
around 40% would accept it. She emphasized that the most effective conversations about
vaccination risks and side effects occur between the pediatrician and the parent, and that
parents should be offered a choice between MMRV and separate MMR plus varicella. The CDC
recommends that pediatricians include these risks in counseling and help families weigh the
benefits and risks for the specific child and situat ion.
10
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.
Dr. Kulldorff acknowledged that there are no data available and that it is difficult to quantify how
much vaccine hesitancy might increase because of additional febrile seizures.

Dr. Meissner noted that the discussion mirrors debate from about 15 years ago and was one of
the few times the ACIP and the American Academy of Pediatrics (AAP) diverged, with the AAP not expressing a preference for the 12– 15 months dose, while the ACIP al lowed the use of
separate MMR plus varicella. He added that a busy pediatric practice might see about one
additional febrile seizure after MMRV at 12– 15 months compared with separate vaccines. He
asked Drs. Su and Oliver to confirm that febrile seizures af ter MMR alone at 12– 15 months
occur at roughly 1 per 3,000 doses and that MMRV increases the risk about twofold.

Dr. Su confirmed that prior studies show an additional risk of about one febrile seizure per
3,000– 4,000 children after MMR and that a twofold increase in risk with MMRV compared with
separate MMR plus varicella is correct.
Dr. Meissner asked to confirm that more than 95% of febrile seizures occur before age 4, with
only a small percentage occurring after age four from any cause.

Dr. Su noted that febrile seizures after age five are rare.
 Dr. Levi proposed that existing records could quantify downstream effects of febrile seizures on
vaccine uptake, since diagnoses identify which children experienced a seizure and
immunization records show subsequent vaccinations. He cautioned that the lower observed risk after the second dose might reflect selection bias if children who reacted strongly to the first
dose delayed or skipped the second dose. He also questioned the field’s limited mechanistic
understanding, noting that a higher varicella antig en dose in MMRV may provoke a stronger
immune response in some children. He asked whether children who experience febrile seizures
have been evaluated for distinctive immune responses or biomarkers to clarify the underlying
mechanisms, emphasizing that saf ety assessment should extend beyond symptoms to a
biological explanation.

Dr. Pollak echoed concerns about limited mechanistic understanding and noted that very young
children may have heightened IL -1–mediated fever responses. He asked whether cytokine
levels were measured in febrile children and whether cytokine gene polymorphi sms or other
genetic predispositions were assessed. He cautioned that second- dose findings may reflect
selection bias if pediatricians avoid revaccinating children with a history of febrile seizures. He
recommended that guidance address how to manage vacci nation schedules for children who
have had prior febrile seizures.
 Dr. Kulldorff agreed with the point that existing medical and immunization records could quantify
whether a febrile seizure affects subsequent vaccination for the child and younger siblings. He
added that he was not aware of any analysis that has examined this to date, though the data
likely exist to do so.

Dr. Milhoan emphasized that febrile seizures are diagnosed retrospectively and that, for
families, a 15 -minute seizure feels incredibly long. He noted that in his practice, families who
have experienced a febrile seizure are often hesitant to proceed with the next vaccine, and he shares their caution. He asked whether fever from natural viral illness shares the exact
mechanisms as vaccine- associated fever, highlighted that rising temperature lowers the seizure
threshold in all people, and questioned whether  the measles vaccine further lowers that
threshold. He observed increased vaccine hesitancy among families and emphasized the
11
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  importance of clearly communicating the risks and benefits of vaccination. He also asked
whether there are long- term follow -up data on children who experienced a febrile seizure after
the first dose.

Dr. Su stated that the request was to present data on the risk of febrile seizures and that he
would need to review data regarding longer -term outcomes.

Dr. Stein asked how risks are communicated to parents and guardians in practice, noting that
some evidence predated the guidelines and additional data have been published since. She
wondered how parental choice is incorporated into those discussions.

Dr. Marin explained that one- pagers were developed to support risk communication: a provider
one-pager in table format outlining risks, benefits, and their implications, and a parent one- pager
noting the increased risk of febrile seizures with MMRV compared to MMR plus varicella. These
materials were designed to help pediatricians discuss options in clear, understandable terms.

Dr. Oliver added that usage data indicate about 85% of children receive separate MMR plus
varicella at the first visit, while roughly 15% receive MMRV. She noted this distribution likely
reflects discussions between pediatricians and parents about risks and benefits.
 Dr. Griffin inquired whether manufacturers or other groups are conducting studies on the
educational performance of children following febrile seizures.

An NCIRD SME shared that the group is not currently doing any long- term studies on the topic.

Dr. Griffin noted that, since the product has been licensed since 2005, it would be helpful to
reassure parents that studies on children’s educational outcomes after febrile seizures have
been conducted. She also asked whether any studies were tested against a trustworthy saline
placebo.

Dr. Su said a follow- up would be necessary to answer the question definitively. Most available
studies compare MMRV with MMR plus varicella.
Dr. Griffin argued that comparing MMRV with separate MMR plus varicella introduces
confounding and makes risk interpretation difficult. She noted the usual rationale that vaccine
versus saline placebo trials are considered unethical once a vaccine is deemed safe and
effective. Still, she contended that, given current levels of parental non- vaccination by informed
choice, an actual placebo- controlled study could be ethical. She suggested inviting parents who
have already chosen not to vaccinate their childre n to participate, to enable a clearer
assessment of the risks.
 Dr. Marin explained that a placebo study would require a randomized controlled trial. Selecting
only parents who avoid vaccination would introduce confounding, as their children may differ
systematically (for example, prior adverse events). Participants cannot be chosen based on
willingness to forgo vaccination; they must consent to random assignment to either the vaccine
or control group.
 Dr. Oliver added that in a randomized controlled trial, participants must have an equal likelihood
of receiving either a placebo or a vaccine, and families must consent to the randomization
process. Given the currently elevated measles activity, asking par ents to accept a chance of a
12
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  placebo, and therefore no protection against measles, mumps, rubella, or varicella, would be
concerning.
 Dr. Griffin thanked Dr. Oliver for her response and shared that, in today’s environment, many
parents are asking for more studies. She suggested that the public would welcome
observational studies comparing vaccinated and unvaccinated children.

Dr. Kulldorff suggested that ethical randomized trials could be conducted by varying the timing
of vaccination rather than withholding it, noting that countries recommend MMR at different
ages. For example, children could be randomized to receive MMR at 12  months versus 18
months, allowing randomized designs without denying vaccination.

Dr. Blackburn asked why trials were designed with MMR and varicella given on the same day,
noting that simultaneous administration might produce adverse event rates similar to MMRV.
She suggested that separating MMR and varicella by at least 28 days could better distinguish
differences in adverse reactions. She asked whether this approach had been considered, given
that typical pediatric visits occur at 12, 15, 18, and 24 months of age.

Dr. Marin explained that trials were designed to compare MMRV with the same- day
administration of separate MMR plus varicella, because MMRV is intended to replace two injections with one. The primary question was whether a single injection would provide
comparable immunogenicity and an acceptable adverse event profile relative to administering
both vaccines at the same visit. While some studies included arms with MMR alone or varicella
alone, most focused on the two practical options parents and providers f ace. Spacing MMR and
varicella across separate visits (for example, at 12 and 15 months) would not answer the
substitution question because children would still receive two injections.
 Dr. Pebsworth inquired whether the MMR/MMRV Vaccine Information Statement states that a
prior febrile seizure or any post -vaccination seizure constitutes a contraindication, noting that
this relates to informed consent. She also referenced VSD findings that included both febrile
and afebrile seizures and questioned whether the lack of statistical significance for second- dose
events at ages 4– 6 years might reflect selection bias. Additionally, she asked whether the
assumption that febrile seizures are largel y benign is clinically justified and whether a history of
febrile seizures should be considered a contraindication to receiving the vaccine again.

Dr. Oliver noted that the MMRV Vaccine Information Statement advises parents to consult their
health care provider if the child has a history of seizures or if a parent or sibling has a seizure
history. She added that the FDA sets contraindications.

Dr. Marin added that the MMRV Vaccine Information Statement includes language under “Risks
of a vaccine reaction”, noting that seizures, often associated with fever, can occur after MMRV.
The risk is higher with MMRV than with separate MMR and varicella when given as a first dose.
The VIS advises that a health care provider can recommend the appropriate vaccines.

Dr. Meissner stated that febrile seizures occur in 3– 5% of children, are familiar to pediatricians,
and have an excellent prognosis. He emphasized that while the episodes are frightening for
families, they are not associated with impaired neurocognitive development, school problems, or
long- term performance issues. He noted that the practical question is whether to use MMRV or
separate MMR plus varicella doses. Combination vaccines can improve completion rates by
reducing the number of injections, whereas s eparating doses may reduce compliance. The
argument against using MMRV at 12– 15 months is a slight increase in febrile seizure risk. He
13
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  supported the current ACIP wording, which allows parents to choose based on their
preferences: those concerned about febrile seizures may select separate MMR and varicella
vaccines. In contrast, those prioritizing fewer injections may choose MMRV. He added  that
about 85% of children currently receive separate MMR and varicella at the first visit and
concluded that the existing guidance is appropriate.

Dr. Levi expressed unease about assumptions underlying current interpretations. He cautioned
that febrile seizures after viral infection may differ biologically from those observed after
vaccination and that measurement alone may obscure important mechanis tic differences. He
urged agencies to investigate mechanisms, including biomarkers, and to follow children who experience seizures over the long term. He noted that higher antigen content may be
associated with more events and recommended that safety asses sments extend beyond 30– 40
days.

Dr. Meissner thanked Dr. Levi and responded that febrile seizures are well -defined: they occur
in children, usually under 5 years (often under 4), are generalized rather than focal, last less
than 15 minutes (typically a few minutes), and do not recur within 24 hours. He noted that most
febrile seizures are not associated with vaccination and that the prognosis is excellent apart
from the emotional impact on families. Given the limited resources and extensive pediatric
experience with these events, he quest ioned whether investing heavily in additional studies on
vaccine -associated febrile seizures would be the most effective use of effort.

Dr. Milhoan cautioned that heavy reliance on ICD codes can be problematic. As a practicing physician, he noted that selecting precise codes is often time -consuming and prohibitive, and
retrospective analyses should account for this limitation. He emphasized the importance of
“clean” data, suggesting a clear distinction between ICD -coded febrile seizures temporally
related to vaccination and those not associated with vaccination. He urged researchers who use ICD-based datasets to acknowledge that these codes  are imperfect and may not fully capture
clinical reality.
 Dr. Pebsworth thanked Dr. Meissner for his comments and clinical perspective; however, she
noted a 2023 study on long- term neurodevelopmental outcomes of febrile seizures reporting
clinical and animal evidence of potential adverse effects, including attention deficit hyperactivity
disorder, increased susceptibility to epilepsy, hippocampal sc lerosis, and cognitive decline in
adulthood, while mechanisms remain unclear. She recommended adding this topic to a future agenda for safety review.
 Rick Haupt, a Merck representative, noted that as a pediatrician, he witnessed fatal
pneumococcal, Hib, and varicella infections before they became vaccine- preventable and
emphasized the importance of not returning to that era. He stated that ProQuad (MMRV ) has
been rigorously evaluated in clinical trials and post -licensure studies, with findings shared with
regulators, public health agencies, and medical societies, and published in journals. He
reiterated that a slight increase in febrile seizures after the first dose was first reported in a 2009
observational study with Kaiser and has informed current recommendations: MMRV is preferred
for the second dose, while separate MMR plus varicella is preferred for the first, with provider or
family choice allowing  MMRV; about 15% choose MMRV at the first visit. He stressed evidence
and consensus that combination vaccines improve series completion and on- time vaccination.
He cited recent CDC data showing kindergarten coverage below the 95% threshold needed for
measl es herd immunity. He cautioned that policies that reduce clarity or consistency around
MMRV could further erode public confidence. Addressing antigen content, he explained that
only the varicella antigen is higher in MMRV (the MMR antigens remain unchanged), which was
14
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  necessary to demonstrate a non -inferior immune response compared with separate MMR plus
varicella, likely due to local antigen interference in the combination product.

Dr. Kulldorff offered a correction, noting that the initial identification of an excess risk of febrile
seizures with MMRV compared with MMR was made at CDC using the Vaccine Safety
Datalink’s rapid cycle analysis. He said the signal was detected after approximately 25,000 doses and highlighted the strong work of the CDC and the VSD in monitoring vaccine safety.

Dr. Hibbeln cautioned that the small risk of febrile seizures —likely without long -term
consequence— must be weighed against the danger of vaccination coverage falling below 90%,
which could lead to devastating outcomes such as fetal loss, neonatal death, and congenital
rubella syndrome. He stressed avoiding actions that might drive nonvaccinating through fear or
oversimplified “for or against” views of vaccines. He emphasized that any major change to long-
standing guidance should have a powerful, clearly art iculated rationale.

Proposed recommendations and discussion
Dr. Martin Kulldorff (ACIP Chair)

Dr. Martin Kulldorff, Chair of the ACIP, presented the proposed recommendations from the
MMRV Vaccine Work Group.
 Proposed Recommendation:

The pediatric vaccine schedule should be updated to reflect the following change:
-For measles, mumps, rubella and varicella vaccines given before age 4 years, the
combined MMRV vaccine is not recommended.
-Children in this age group should receive separate measles, mumps, and rubella
vaccine and varicella vaccine (MMR+V).

Discussion
Dr. Stein asked how the proposed recommendation differs from current guidance, noting that
the 2009 recommendation appears to call for two separate shots for the first dose.
Dr. Kulldorff outlined two differences. First, the proposal states that both options are acceptable,
with a preference for MMR plus varicella for doses administered between 12 and 47 months of
age. Second, for children who receive a “second” dose before age 4 (for example, after an early
outbreak dose at 7 months followed by a dose at 12– 15 months), that dose would be treated as
a pre -4-year dose so that the preference would be separate MMR plus varicella rather than
MMRV.
Dr. Levi stated that if adherence were guaranteed to be the same, separate MMR plus varicella
doses would be preferable, given the added adverse events with MMRV and the lower antigen
exposure with separate vaccines. He questioned whether separating the fi rst-dose vaccines
meaningfully reduces adherence, suggesting that safer profiles likely increase trust and
adherence. In the absence of strong evidence either way, he favored the option that appears
safer.
Dr. Pebsworth sought confirmation that at the first visit (12– 15 months), approximately 85% of
vaccinations are administered as separate MMR plus varicella and about 15% as MMRV.
Dr. Kulldorff confirmed that at the first visit (12– 15 months), about 85% of vaccinations are
administered as separate MMR plus varicella, and roughly 15% as MMRV. He commended
15
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  pediatricians and nurses for prioritizing the option associated with fewer febrile seizures and
shared a brief personal example illustrating providers’ awareness of the rationale.
Dr. Meissner shared two points. First, an MMR dose given before 12 months is intended for infants traveling to measles -endemic areas and does not count toward the routine two -dose
series; those children still need doses at 12– 15 months and 4– 6 years. He al so clarified that
MMRV is licensed only for ages 12 months through 12 years. Second, he cautioned against
removing parental choice for the first dose, noting that while about 85% currently receive
separate MMR and varicella, some parents prefer a single vi sit with MMRV, and that option
should remain available.
Dr. Goldman inquired whether a fully vetted Evidence to Recommendations (EtR) presentation
would be provided, addressing harms, benefits, acceptability, and feasibility, with input from
practicing clinicians and liaisons. He argued the proposed recommendat ion could confuse the
public, does not reflect real -world clinician experience with vaccine hesitancy, and might enable
insurers and the Vaccines for Children program to decline coverage. He added that the change
would remove parental choice for informed decision -making with their physicians. He urged the
committee not to change recommendations and, if proceeding, to use the established EtR process with transparent data to support debate and discussion.
Dr. Hopkins agreed with Dr. Goldman.
Dr. Middleman endorsed Dr. Goldman’s comments and emphasized the need to present all available evidence in a single, coherent, and scientifically vetted format, so that providers and
patients can understand the full scope of information. She emphasized the  importance of
focusing on what the evidence reveals rather than beliefs unsupported by evidence.
Dr. Kulldorff thanked Dr. Srinivasan and Dr. Su for their excellent and informative presentations.
Dr. Levi requested clarification on what information had not been discussed or considered,
noting that prior comments had implied missing data. He asked whether anyone is disputing the
evidence of increased febrile seizures after MMRV, and what additional data they believe
should be reviewed.
Dr. Goldman argued that the discussion was not thoroughly vetted and relied too narrowly on
selected data points without incorporating real -world clinical experience. He noted that liaison
members have been removed from work groups, reducing subject matter  expertise and the
patient voice. He emphasized that a complete assessment should address implementation,
acceptability, feasibility, equity, and the balance of harms and benefits, and urged inclusion of
physicians’ practical experience with patients.
Dr. Middleman echoed Dr. Goldman’s comments and requested that all available evidence be
presented together, encompassing the full extent of scientific literature rather than only the few
studies discussed.
Dr. Levi responded that he trusts the CDC staff to have presented all relevant data and noted that several colleagues are pediatricians with experience in patient care. He invited anyone who
believes information is missing to specify it so the committee can consider it.
Dr. Hopkins appreciated the CDC data, describing it as thorough and informative, but noted that equity considerations and the practical implications for patients and practicing physicians had
not been adequately addressed. He stated that without a full Evi dence to Recommendations
(EtR) review of these elements, the committee lacks a complete basis for decision- making.
Dr. Goldman agreed with Dr. Hopkins.
16
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Jshlay emphasized practical considerations at the 12- month visit, noting that children may
receive multiple vaccines and some parents prefer fewer injections. She estimated that up to 7
vaccines can be given at a single visit and underscored the need f or informed consent and
alignment with parental preferences when scheduling and selecting vaccines.
Dr. Stein noted that the Vaccine Information Statement indicates an increased risk of fever and
seizures after the combined MMRV shot compared with separate MMR and varicella shots. She asked how this risk is communicated to parents in practice and whether  clinic time pressures,
such as busy patient flow, ever limit the ability to provide clear informed consent. She invited
input from medical professionals on how these discussions are handled.
Dr. Milhoan suggested asking parents directly about the adequacy of risk and benefit
discussions rather than relying solely on clinicians’ perspectives. He noted that in busy
practices, informed consent is often incomplete across various medicines and vacc ines, with
rare but serious risks not always being thoroughly reviewed. He said that many parents felt they were given little information and concluded that current practices may not fully meet the
standard for informed consent.
VFC Resolution Update: MMRV Vaccine
Jeanne Santoli (CDC/NCIRD)

Jeanne Santoli (CDC/NCIRD) presented the VFC resolution update with all revisions from the
previously approved resolution shown in red. The purpose of the update is to provide revised
guidance on the use of the combined measles, mumps, rubella, and varicel la (MMRV) vaccine.
The resolution includes three components: MMR, varicella, and the combined MMRV. No changes were made to the MMR or varicella components; eligibility, recommended schedules,
dosage intervals, contraindications, and precautions remain the same. The changes apply only
to the combined MMRV component and clarify eligible groups, recommended schedule,
dosage, and contraindications to align with the proposed recommendations under discussion
today by the ACIP.

Discussion
Dr. Kulldorff noted that, as is standard procedure, two votes will be conducted. The first will address the recommendation, followed by a separate vote on the VFC resolution. He added that
this approach is consistent with the process used during the June m eeting.
Dr. Griffin echoed comments from Dr. Milhoan, noting from her personal experience as a mother
that vaccine information statements were not always consistently explained when her children
received immunizations, with the expectation that parents would read the handout
independently. She added that many of her patients and non- physician acquaintances had
reported similar experiences, although she acknowledged that this was anecdotal. Dr. Griffin
emphasized the value of having additional data for committee rev iew and clarified her earlier
comments regarding randomized controlled trials, acknowledging the ethical limitations of such
studies. She concluded by stressing the importance of considering a broader range of studies
and raw data, as well as individual ex periences that collectively inform the balance of vaccine
benefits and risks.
Dr. Jshlay shared that at the Public Health Institute of Denver Health, her large- scale
immunization program provides the VFC and VIS forms before vaccination and reviews them
with patients to ensure informed decision- making. She emphasized that providing the VIS
before vaccination is a requirement and noted that local public health agencies across the
country follow this same practice. She added that, although she could not comment on
anecdotal reports, her clinic strives to uphold this standard.
17
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Middleman emphasized the importance of grounding public health recommendations in a
comprehensive body of data rather than anecdotal evidence. She noted that while physicians
focus on individual patients, public health decisions must consider the healt h of the entire
population. She highlighted the breadth of studies that inform the evidence -to-recommendation
process and stressed the need to evaluate all elements of public health, including disease
impact, risks and benefits, feasibility, acceptability,  cost-benefit ratio, and equity. Dr. Middleman
questioned the urgency of deciding at this meeting and urged the committee to follow a
methodical evidence -to-recommendation process to ensure scientific rigor and maintain public
confidence.
Dr. Kulldorff apologized for sharing an anecdote about his twins’ vaccinations but noted that the
committee had engaged in a strong, science -based discussion. He commended the CDC
colleagues for their presentations and highlighted the quality of the debate  on various aspects of
the vaccines.
Dr. Pebsworth acknowledged that at the 12– 14-month visit, many vaccines are administered
and noted that approximately 85% of pediatricians and parents currently choose MMR plus
varicella separately. She then raised a technical question regarding the language of the posted
vote, which states “recommends.” She sought clarification on whether this language would
prohibit the use of the FDA -licensed MMRV vaccine for certain patients, emphasizing the
importance of preserving provider discretion to administer lic ensed products.
Dr. Kulldorff clarified that the committee’s role is to make recommendations, while the FDA determines which vaccines can or cannot be used. He noted that committee votes may have
consequences for insurance coverage, including through CMS, but emphasized t hat the
authority to approve vaccine use rests with the FDA.
Dr. Srinivasan suggested that it would be helpful for a VFC representative to comment on how
ACIP recommendations affect the Vaccines for Children program, given that the program funds
many pediatric vaccines.
 Dr. Santoli explained that if a vaccine is designated as “not recommended,” it will not be
covered under the VFC program for children. She noted that while there are ways to address
individual -based decisions that allow for coverage, the current resolution under consideration
would mean that VFC would not cover the vaccine even if a parent and physician chose it.

Dr. Johnson added that a “not recommended” designation could also affect coverage under
Medicaid and the Children’s Health Insurance Program, as well as individual and group
insurance markets. She noted that this could impact overall coverage and potential ly result in
out-of-pocket costs, such as co -pays.

Dr. Kulldorff clarified that the coverage discussion pertains specifically to the MMRV vaccine. He
emphasized that coverage for the MMR and varicella vaccines will remain unchanged, with both
continuing to be fully covered.

Dr. Johnson confirmed.
 Dr. Hibbeln requested clarification that under the proposed change, administration of the MMRV
vaccine before four years of age would be considered “not recommended,” and therefore would
not be covered for payment.
 Dr. Santoli clarified that, under the Vaccines for Children program, the MMRV vaccine would not
be covered for children under the age of four.
18
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.
Dr. Hibbeln expressed concern that under the proposed change, parents would lose the option
to choose the MMRV vaccine for their child unless they were willing to pay out of pocket. He
noted that if parents preferred a single vaccination rather than multiple shots, this option would
effectively be taken away despite their understanding of the risks and benefits.

Dr. Santoli confirmed that VFC would not cover the vaccine for those children.

Vote: MMRV Vaccines Vote
Dr. Martin Kulldorff (ACIP Chair)  read the following proposed ACIP voting language for
MMRV vaccines into the record:
The pediatric vaccine schedule should be updated to reflect the following change:
-For measles, mumps, rubella and varicella vaccines given before age 4 years, the
combined MMRV vaccine is not recommended.
-Children in this age group should receive separate measles, mumps, and rubella
vaccine and varicella vaccine (MMR+V).

Motion/Vote: MMRV Vaccines

Dr. Levi motioned to approve the recommended voting language, stating,
“The pediatric vaccine schedule should be updated to reflect the following change:
-For measles, mumps, rubella and varicella vaccines given before age 4 years, the combined
MMRV vaccine is not recommended.
-Children in this age group should receive separate measles, mumps, and rubella vaccine and
varicella vaccine (MMR+V).”
Dr. Pagano seconded the motion. No COIs were declared. The motion carried with 8 votes in
favor, 3 votes opposed, and 1 abstention. The disposition of the vote was as follows:

    8 Favored:  Pagano, Milhoan, Stein, Griffin, Pollak, Pebsworth, Levi, Kulldorff
    3 Opposed:   Blackburn, Hibbeln, Meissner
    1 Abstained:  Malone
 Discussion
 Dr. Santoli requested clarification on the wording used during the vote discussion, noting that
she had heard the term “compensate” and wanted to ensure it was understood correctly. She
explained that a yes vote would align the VFC resolution with the recommendation vote that had
already passed, meaning the combination vaccine would not be covered in VFC for children
under four years of age. A 'no' vote would maintain the current VFC coverage as it stands today,
which includes the combination vaccine for children aged 12 months through 12 years. She
acknowledged that timing issues had prevented the full written materials from being available
before the meeting, as the resolution had to be made late the previous evening to align with the
committee’s proposed language.

A CMS representative confirmed that the same coverage decision would apply to Medicaid,
CHIP, and the individual and small group markets, clarifying that the combined vaccine for
children under four years would not be covered if the resolution were to pass .

19
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Meissner expressed confusion, asking what would happen if the committee voted no, and
emphasized the need for clarity.
 Dr. Santoli reiterated that a no vote would maintain VFC coverage unchanged, meaning the
combination vaccine would remain covered; however, CMS and VFC could ultimately have
different coverage policies, potentially creating confusion.

Dr. Malone commented that it was difficult for the committee to vote without a written text of the
resolution, even though the presentation was clear, and suggested that complete written
information be provided in the future.

Dr. Pagano sought clarification on whether a recommendation automatically leads to
reimbursement.

Dr. Levi stated that his understanding was that there are two parallel decisions: the
recommendation and the resolution. If no new approval is granted, the previous decision
remains in effect.

Dr. Pagano noted that this process seemed convoluted, as the committee was being asked to
vote no to maintain coverage.
 Dr. Milhoan requested clarification on the relationship between the VFC and CMS programs. Dr.
Santoli explained that VFC covers Medicaid, uninsured children, American Indian and Alaska Native children, and underinsured children served in federally qualified health centers, while
CHIP is administered separately under CMS.
 A CMS representative confirmed that CHIP and the individual markets are not directly affected
by this vote but rather by the broader ACIP recommendation.

While there was a VFC vote on the initial day of the meeting, with the results of 1 in favor, 8
opposed, and 3 abstained, the committee decided to reconsider the vote due to not fully
understanding the implications. Dialogue to follow:

Dr. Kulldorff noted that most members were still new to ACIP and might not yet grasp specific
technical issues. He explained that after the meeting, a member had raised concerns about the
second vote taken on the VFC resolution regarding the MMRV vaccine a nd whether the
committee had fully understood the implications. He stated that VFC votes are typically aligned to ensure equal coverage and access for all children, and that some consideration had been
given to resolving the conflicting votes.

Dr. Pebsworth moved to reconsider the VFC resolution on MMRV that had been voted on the
previous day.
 Dr. Griffin seconded the motion.

Dr. Kulldorff explained that the committee would first vote on whether to reconsider the matter. If
that vote passed, the resolution itself would then be voted on a second time. He asked
members to state their names, declare any conflicts of interest, and indicate their votes. Results
to follow:

20
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Vote: To Reconsider the original MMRV Vaccines-  VFC Vote

Motion/Vote: MMRV Vaccines

Dr. Pebsworth motioned to reconsider the VFC resolution vote voted on September 18, 2025.
Dr. Griffin seconded the motion. No COIs were declared. The motion carried with 10 votes in
favor, 0 votes opposed, and 2 abstentions. The disposition of the vote was  as follows:

    10 Favored:      Levi, Pebsworth, Hibbeln, Pollak, Griffin, Stein, Blackburn, Milhoan, Pagano,
Kulldorff
    0 Opposed:
    2 Abstained:  Malone, Meissner

Discussion
Dr. Goldman, representing the American College of Physicians, expressed concern about the
vote taken the previous day because the committee had two conflicting votes on the same
resolution, with the second primarily affecting children from lower socioeconomic backgrounds.
He questioned whether the outcome of the first vote implied that children from lower
socioeconomic groups should only receive what the committee had described as a harmful
vaccine, or whether the second vote revealed that there was no evidence of harm from MMRV
and that the risk was not a concern. He argued that the second vote should be considered valid
for the entire population, as it indicated that there was insufficient data to support claims of
harm.

Dr. Levi stated that the chair had already explained there was an error in the interpretation of
the votes and suggested that the committee focus its time on scientific debate rather than
pursuing discussion without merit.
 Dr. Hibbeln stated that the committee had acknowledged the wording of the second vote was confusing and imprecise. He remarked that, considering the extensive work by CDC and the
committee, the confusion was mainly due to wording and expressed appreciation for the more
precise phrasing now provided.

Dr. Kulldorff emphasized that the vote’s outcome ensures every child, including those in the
Vaccines for Children program, will have access to vaccination against measles, mumps,
rubella (also known as German measles), and varicella (chickenpox). He stated that this guarantees all children will be able to receive protection against these four critical diseases.
 Vote: MMRV Vaccines - VFC Vote
Dr. Martin Kulldorff (ACIP Chair)  read the following proposed ACIP voting language for
MMRV vaccines into the record:
Approve the updated Vaccines for Children (VFC) resolution for prevention of measles,
mumps, rubella and varicella.

Motion/Vote: MMRV Vaccines

21
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Levi motioned to approve the recommended voting language to approve the updated
Vaccines for Children (VFC) resolution for prevention of measles, mumps, rubella and
varicella. Dr. Pebsworth seconded the motion. No COIs were declared. The motion carried
with 9 votes in favor, 0 votes opposed, and 3 abstentions. The disposition of the vote was as
follows:

   9 Favored:  Levi, Pebsworth, Hibbeln, Pollak, Griffin, Stein, Milhoan, Pagano, Kulldorff
   0 Opposed:
   3 Abstained:  Blackburn, Malone, Meissner

HEPATITIS B VACCINE S
 Introduction
Dr. Martin Kulldorff (ACIP Chair)
ACIP Chair Dr. Martin Kulldorff  opened the session by introducing the Hepatitis B Vaccine. He
explained that the focus of the discussion today  was very specific: to evaluate only the birth
dose of the hepatitis B vaccine given within 24 hours of birth, and only for infants whose
mothers have tested negative for hepatitis B. He clarified that no changes are being considered
for infants born to mothers who test positive or whose status is unknown.
Hepatitis B Birth Dose Vaccination
Dr. Adam Langer (CDC/NCHHSTP)

Dr. Adam Langer (CDC/NCHHSTP) presented on Hepatitis B birth dose vaccination. Hepatitis B
virus (HBV) infection causes hepatitis B, which affected an estimated 254 million people
worldwide in 2022. While some infections clear naturally, many progress to chronic hepatitis B,
an incurable condition that can lead to severe liver disease, liver cancer, and death.
 HBV can be transmitted from mother to child (perinatal transmission) as well as through household or community exposure. [hepatitis B is easily transmitted through relatively casual
contact; sexual contact or sharing of needles is not required to transmit the virus to others.]
Without intervention, up to 85% of infants born to HBV -infected mothers will become infected.
Risk of developing chronic infection is highest in children: about 90% of infants perinatally
infected develop chronic hepatitis B, and roughly 25% infected in childhood die prematurely from related complications.  [Likelihood of chronic infection increases inversely with age, so the
youngest children (i.e., newborns and infants) are at greatest risk.]

In the U.S., an estimated 2.4 million people are living with hepatitis B, about half unaware of
their infection. Roughly 70% of those with chronic hepatitis B were born in countries with intermediate to high prevalence, often infected at birth or early chi ldhood.  [Chronic hepatitis B is
incurable and can ultimately be fatal, so immunization against hepatitis B is lifesaving, and the earlier in life the vaccination series is started, the more lives that will be saved and severe
chronic illness that will be p revented.]

22
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Vaccination programs have reduced hepatitis B among U.S. children, but most reported cases
now occur among unvaccinated adults. In 2023, about 14,400 acute cases were estimated, with
the highest rates in adults aged 40– 59 years.

Chronic hepatitis B carries significant healthcare costs. Analysis of claims data from 2004 to
2015 showed annual per -patient costs (adjusted to 2015 dollars) ranging from approximately
$94,000 for less severe disease to roughly $325,000 for those requiring a liver transplant.
Overall, more than $1 billion is spent annually on hepatitis B -related hospitalizations in the U.S.

Two products prevent perinatal hepatitis B virus (HBV) infection: the hepatitis B vaccine, which
provides long- term protection and is used for both pre - and post -exposure prophylaxis, and
hepatitis B immune globulin (HBIG), which offers temporary protection in specific post -exposure
settings.

When used together, vaccination and HBIG prevent about 94% of mother -to-child
transmissions. The hepatitis B vaccine is the cornerstone of prevention, with effectiveness
increasing the sooner the birth dose is given after delivery.

The hepatitis B vaccine, available in the U.S. for more than 40 years, was the first vaccine to
prevent infection with a cancer -causing virus. Two single- antigen recombinant vaccines are
FDA-approved for use from birth: Recombivax HB (1986) and Engerix -B (1989). [These
vaccines were tested using placebo- controlled randomized trials prior to licensure in the United
States, so there is no need to do additional placebo- controlled studies now.] Extensive research
and reviews by the Institute of Medicine and WHO  confirm the vaccine’s safety and
effectiveness.  [The vaccine has been routinely given to all newborns in the United States since
1991, and very few serious adverse effects of the vaccine have been identified over the 34 years that this vaccine has been in routine use. The worst reported adverse effect,  anaphylaxis,
is literally a one in a million occurrence, and this extremely rare reaction can be addressed with
immediate treatment and causes no long- term injury to the vaccinated person.]

Full hepatitis B protection requires a multi -dose series, typically three doses. Protective antibody
responses are seen in 25% of infants after the first dose, 63% after the second dose, and 98% after the full three- dose series. Immunity can last for decades; one Alaska- based study showed
that more than 90% of individuals retained protection over 30 years after vaccination.  [The
sooner the vaccination series is started, the sooner that the child is protected.]

Since 1988, universal screening for hepatitis B surface antigen (HBsAg) has been
recommended for pregnant women, with additional testing for at -risk women later in pregnancy
or at delivery. Vaccination at birth has been recommended since 1984 for infants o f women
testing positive, with the timing specified as within 12 hours of birth starting in 1988. HBIG administration has also been recommended within 12 hours for infants of HBsAg- positive
women since 1984, and since 2018 for infants under 2,000 grams bor n to women with unknown
results.

In 1991, the U.S. adopted universal infant hepatitis B vaccination. Guidance on the timing of the
birth dose has evolved from “before hospital discharge but no later than 2 months” (1991), to
“administered in the birth hospital” (2005), to “within 24 hours  of birth” (2018).
 The universal hepatitis B birth dose provides a critical safety net for infants who may have
unrecognized HBV exposure during pregnancy or early childhood, which can lead to severe
outcomes. Gaps in post -exposure prophylaxis occur due to lack of prenatal c are, missed
23
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  screening, or administrative errors. One reported case involved a mother with a positive test
result that was miscommunicated, resulting in her infant not receiving prophylaxis and later
dying from fulminant hepatitis. Between 1999 and 2002, more than 500 similar transmission
events were documented when prophylaxis was not administered.

In the U.S., 12– 16% of pregnant women receive inadequate or no prenatal care, and a similar
percentage are never tested for hepatitis B. The national perinatal hepatitis B prevention
program identifies less than half of infants born to HB sAg-positive mothers annually,
underscoring the importance of universal birth dose vaccination.

The birth dose also protects against household or community transmission. HBV can survive for
over seven days on surfaces, and even microscopic amounts of blood or body fluid are
sufficient to transmit the infection. Unvaccinated infants are at risk if they live with or are cared
for by individuals with chronic HBV, many of whom are unaware of their infection. Studies
before widespread use of the birth dose showed 7– 11% of U.S. -born children of immigrant
mothers with no HBV evidence tested positive, pointing to community exposure.  [Even for
infants born to mothers known to be HBsAg- negative, the birth dose and subsequent doses
provide crucial protection against household and community (e.g., daycare) exposures that
could occur as soon as the infant leaves the hospital.]
 Initiating the hepatitis B series on the first day of life offers early protection and benefits infants
of both positive and negative mothers. It poses no increased risk of adverse events compared to
later vaccination.

Over t hree decades of data- driven, evidence- based hepatitis B vaccination recommendations
for newborns and infants have led to significant reductions in U.S. acute hepatitis B cases. Following the 1991 recommendation for universal infant vaccination (within 12 hours for infants
of mothers with unknown status), the number of reported acute cases fell by 69%, from 18,003
in 1991 to 5,494 in 2005. Following the 2005 guidance to administer the first dose before
hospital discharge, later updated in 2018 to withi n 24 hours of life, cases dropped an additional
60% to 2,214 in 2023. However, after adjusting for underreporting, the estimated actual number
of 2023 cases was 14,400.

Rescinding the universal birth dose recommendation poses risks, including more perinatal HBV
transmission, increased lifetime risk of severe liver disease, added administrative complexity,
gaps in care, reduced vaccine series completion, and higher lifetim e healthcare costs. Harms
would fall disproportionately on uninsured or low -engagement patients. The only potential
benefit is a reduction in already rare adverse events; serious events, such as anaphylaxis, occur
at a rate of 1.1 per 1 million doses.

CDC was asked to address four specific questions related to the hepatitis B birth dose. The first
two questions, reviewed in this session, concern hepatitis B vaccination recommendations in
developed countries: specifically, the recommended age of the firs t dose for infants born to test -
positive mothers and for all other infants, and the prevalence of hepatitis B infection among
pregnant women. The remaining two questions will be addressed later by colleagues from the
Immunization Safety Office.
 Countries differ in their approaches to the birth dose. Some recommend a universal birth dose
for all infants regardless of maternal status, others recommend it only for infants of HBV -positive
mothers, some provide a universal birth dose in limited regions, and some have no
recommendation at all. Currently, 43 countries do not have a birth dose policy; however, with
24
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Gavi support beginning in 2024, many of these countries are either introducing the birth dose or
have expressed plans to do so within the next three to five years.
 Among the 38 countries reviewed by ACIP, 36, including the U.S., recommend a birth dose
within 24 hours along with HBIG for infants born to HBV -positive mothers. The only exceptions
are Ireland and Denmark, though both generally provide the vaccine within 24 hours. For infants
born to test -negative mothers, eight countries provide a universal birth dose within 24 hours. Of
the 38 countries, 26% limit the birth dose to infants of HBV -positive mothers but still recommend
routine infant vaccination later. Canada’s policies differ by province. Only four countries,
Denmark, Finland, Iceland, and New Zealand, limit the birth dose to infants of HBV -positive
mothers and do not offer universal infant vaccination.

The most recent prevalence data from 2023 or the past 10 years for hepatitis B among pregnant
women were available in 20 of the 38 countries. Nine reported prevalence below 0.5% and all
used selective birth dose policies. Eight countries reported prevalenc e between 0.5% and 0.9%,
while three reported prevalence greater than 2%. No U.S. prevalence data have been available
in the past 10 years. Only six of the 38 countries maintain national registries to track HBV
prevalence in pregnant women, while the other  32, including the U.S., do not collect this data
regularly.

Screening data were available in 19 of the 37 comparator countries. Several countries met the
2030 global target of screening 90% or more of pregnant women. In the U.S., an estimated 14%
of pregnant women are not screened, placing the U.S. below the target . The U.S. is one of five
countries not meeting the goal and one of only three without universal healthcare coverage.
Unlike the U.S., most countries provide universal health coverage, ensuring access to prenatal
care and vaccination, which supports higher  screening rates and timely prophylaxis. This
difference highlights the importance of the universal birth dose in the U.S. as a safety net for
infants born to mothers with unknown HBV status. Notably, no country has reverted from
universal to selective bir th dose, and several are moving toward universal adoption.
The second question requested a systematic review of randomized trials on administering the
hepatitis B vaccine within 24 hours of birth. The updated review screened 1,390 studies in
addition to 833 from the existing review. Seventeen studies met the inclusion criteria, including
seven from the earlier review and 10 from the update.

The risk of bias assessment revealed a high overall risk, primarily due to unclear methods of
randomization and limited reporting on whether investigators were blinded to the outcomes,
which could impact the results. The 17 studies were grouped by intervention type, including
efficacy, timing of vaccination, product or formulation differences, dose and schedule, and HBIG
co-intervention. Outcomes of interest included protection, efficacy, and safety.

Efficacy trials demonstrated high levels of protection among infants born to HBV -positive
mothers. Birth dose vaccination alone reduced transmission by up to 94% and combining the vaccine with HBIG reduced transmission by up to 99%. Adverse events were few  and generally
mild, such as low -grade fever.
 A timing study among infants of HBV -negative mothers compared vaccination at birth, 2
months, or 6 months, with a control group starting at 18 months. All timing groups showed high levels of protection (91%) with no significant safety differences.

25
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Several product and formulation trials comparing different hepatitis B vaccines found them to be
non-inferior. Across studies, high levels of seroprotection and equivalent efficacy in preventing
perinatal transmission were observed, with few reported adver se events.

Dose and schedule trials showed strong seroprotection in both HBV -positive and HBV -negative
infants. One study reported 96% seroprotection in the intervention arm compared to 0%
seroprotection in the comparator arm with no birth dose. Efficacy was consistently high across
groups, and safety profiles were similar, with very few local or systemic adverse events.

The updated systematic review did not identify any new placebo- controlled trials assessing
efficacy, which is unsurprising since the vaccine’s efficacy was established in the 1980s, and
withholding it would be considered unethical. There was limited report ing for pre- term, low
birthweight, and extremely low birthweight infants, and no morbidity or mortality outcomes were
reported. The studies were heterogeneous, and many were conducted before the CONSORT
statement was widely adopted, resulting in weaker reporting standards. The risk of bias was
primarily associated with randomization and outcome measurement; however, even studies with
a high risk of bias can provide helpful information if the findings are consistent and the effects
are significant.

Dr. Langer concluded that the body of evidence from both the existing and updated systematic
reviews supports the birth dose as safe, effective, and capable of inducing strong seroprotection
in infants born to mothers who are both test -positive and test -negative. CDC interprets these
findings as continued support for the ACIP’s universal birth dose recommendation, first made in
1991 and later strengthened in 2005 and 2018 as part of the national strategy for hepatitis B
elimination.
 Discussion

Dr. Griffin asked how many of the 17 studies included in the review had declared a conflict of
interest.
 Dr. Nyendak , an SME who oversaw  the rapid systematic review, stated that, to her knowledge,
there were no reported conflicts of interest but noted they would confirm and provide that
information later.

Dr. Griffin noted that the ACIP group does not have open access to journals, and purchasing
individual studies can cost $45 to $60 each, which becomes a significant barrier when reviewing
hundreds of studies. In reviewing the 17 studies included in the systematic review, she found
that eight declared conflicts of interest. Among the studies focused on adverse events, five of
the eight had declared conflicts, while three others had unclear declarations. Several involved
pharmaceutical funding, where companies both funded the study and provided the vaccine. She
expressed concern about this issue and then referenced CDC data, stating that there were 912
hepatitis B -related deaths in 1991, the year the vaccine was approved, compared to 1,740
deaths in 2021. She asserted  that percentage rates indicate an increasing death rate despite
the adoption of the vaccine and asked what accounts for this change.

Dr. Nyendak  clarified that  after conferring with the systematic review team in real time,  the team
was aware of three studies that reported conflicts of interest and provided this as a correction to
the record.

26
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Wester from the Division of Viral Hepatitis stated that the team would investigate the
question further regarding hepatitis B death rates. She noted that, for surveillance purposes,
reportable death rates come through the National Vital Statistics Syst em and that reporting
practices have evolved significantly over the decades referenced.

Dr. Levi reviewed the data by age group and noted that vaccination of infants born to HBV -
positive mothers clearly reduced cases in children aged 0– 19. However, he observed that after
the 2005 recommendation for universal birth dose, further reductions mai nly appeared in older
age groups rather than in young children. He questioned whether the data demonstrate an
added benefit of universal vaccination at birth for infants of test -negative mothers living in typical
environments. Dr. Levi emphasized that the vaccine is critical for infants born to HBV -positive
mothers and other high- risk populations but expressed uncertainty about the evidence
supporting universal administration to all newborns.
 Dr. Langer responded to Dr. Levi, identifying two questions: why declines are more visible in
older age groups than in younger ones, and whether there are data on community and
household exposures. He explained that the observed declines in older groups reflect a birth
cohort effect, where individuals vaccinated as infants in the early 1990s have since aged into
older cohorts. As time passes, those who benefited from early vaccination policies move into
older  age categories, which explains the shifts seen i n the data.
 Dr. Levi observed that since universal birth dose vaccination began prior to hospital discharge in
2005, infants born after that year would not yet have aged into the older cohorts where declines
are being measured. He suggested that any measurable impact of the universal policy may not
be evident until these cohorts are older. He noted that current data may not yet show a
meaningful effect.
C
Dr. Stein asked about the incidence of hepatitis B in children born to mothers confirmed as
hepatitis B negative, noting this would help understand the risk. She also pointed out that only
two of the reviewed clinical trials specifically stratified childre n born to negative mothers, and
both were rated as high risk of bias. She asked how reliable the data are on hepatitis B
incidence in this group.

An SME referred to slide 30, noting that in dose and schedule trials involving infants of hepatitis
B surface antigen– negative mothers, efficacy was equivalent between intervention and
comparator groups. The randomized efficacy literature has focused more on infants of surface
antigen– positive mothers, where outcomes such as seroprotection, efficacy, and safety are
more measurable and show larger effect sizes. Infections among infants of negative mothers
typically result from missed or late maternal infecti on or early horizontal exposure from a
household member or caregiver. This underscores the rationale for a universal birth dose as a
safety net. Data have shown a 7– 11% prevalence of infection among U.S. -born children of
immigrant mothers with no evidence of maternal infection, reflecting community or household
transmission as the only plausible explanation. The universal birth dose policy was adopted
after risk -based strategies failed to prevent perinatal and early childhood transmission, with only
26% of acute hepatitis B cases linked to a reported risk factor , [and the universal birth dose
policy has been demonstrated to be highly successful in reducing incidence of new hepatitis B
infections in the United States.]
 Dr. Kulldorff commented that although U.S. data on hepatitis B prevalence among pregnant
women were not available, estimates based on women aged 20– 40 suggest a prevalence of
about 4– 5% overall, with less than 0.1% among U.S. -born women. He noted that roughly 80%
27
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  of infections are among immigrants and 20% among U.S. -born women, emphasizing that U.S.
rates are very low compared to Western European countries, where only Portugal has a
universal birth dose policy. He also reviewed adverse event data, noting five local ized and ten
systemic events among 178 vaccinated infants compared to three localized and four systemic
events among unvaccinated infants. Although overlap between localized and systemic events
was unclear, combining them produced a borderline statisticall y significant result (p = 0.054)
with a relative risk slightly above two. Although the sample size was small, the data suggest
somewhat higher adverse events for infants vaccinated at birth, which should be considered in
deliberations.
 Dr. Levi inquired about the duration of the clinical trials for safety monitoring and the
surveillance time window for these results.

Dr. Kulldorff responded that he believed it was short -term.

Dr. Levi then asked whether the short -term safety monitoring period in the trials was only a few
days, such as up to five, and clarified that if so, the data may suggest higher adverse events in the first days after vaccination but provide no information beyond that period.

An SME directed participants to slides 44 and 45, which show sample sizes and follow -up
periods in months. Most safety data were collected after the first dose, with monitoring beginning at 24 hours. The follow -up periods were  shown for study  and ranged from five to 24
months.
 Dr. Levi asked whether data from the longer follow -up periods could be used to compare
adverse events overall.

SME responded that the studies reported safety outcomes for as long as each study continued.

Dr. Milhoan asked what specific signals were being tracked during follow -up, noting that if the
period extended to 24 months, it would be important to know whether the criteria included
hospitalizations, fevers, hepatitis, or other potential adverse reacti ons, especially since children
would have received additional vaccines during that time.

SME explained that slide 41 of the extra slides shows the time points used in the studies.
Seroprotection was reported at the first time point after the last dose in the series. Efficacy was
measured at the latest available time point with the ongoing intervention, and safety was assessed at birth at the closest time point immediately after the birth dose, as  requested.

Dr. Milhoan asked if it was for seroprotection rather than side effects.
 SME clarified that it referred to the follow -up period.
 Dr. Levi requested clarification on whether there were any follow -up reports of side effects
beyond the first few days after birth.
 SME responded that follow -up varied across studies and said they would provide clarification
later.

Dr. Wester responded to questions about the prevalence of hepatitis B infection in the U.S. She
explained that there is no disease surveillance registry to answer this directly, but NHANES data
28
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  from 2013– 2018 estimated national prevalence at 0.3%. She noted this may underrepresent
populations with the highest burden. Stratification revealed a similar prevalence among males
and females, as well as among reproductive- age adults (25– 49 years). By co untry of birth,
prevalence was 0.1% for U.S. -born individuals and 1.2% for non- U.S.-born individuals. A
modeling study estimated that in 2015, approximately 0.5% of U.S. births were to women who
were HBsAg -positive, with 40% of these women being U.S. -born and 60% non- U.S.-born. She
also noted that evolving recommendations over the past three decades have had a generational
impact. Finally, she clarified that the 1991 infant vaccination recommendation was intended for
administration before hospital discharge . However, it allowed vaccination up to two months of
age, with a preference for vaccination before discharge.

Dr. Malone asked if there were data on the number needed to treat to prevent a case of
hepatitis B in a child born to an HBsAg- negative mother in the U.S. population.

Dr. Wester replied that such data are  not available. She noted, however, that if delaying the first
dose for infants of test -negative mothers were considered, it would be important to have
modeling data to estimate potential harms from unrecognized exposures during pregnancy or
early childhood.

Dr. Malone added that to assess the risk -benefit reasonably, more granular data on the number
needed to treat for infants of mothers with negative test results are required, as well as a clear risk analysis of potential adverse events and their incidence r ates for the vaccines.

Dr. Wester clarified that there is no data on new cases associated with delaying the birth dose
recommendation to one month of age.
 Dr. Kulldorff asked whether the FDA has any information on this and suggested it may be fair to
say no.

Dr. Hoeg  noted that the original clinical trial data from the 1980s, which appear on the product
label, only included short -term follow -up of four to five days. She stated that this makes it
difficult to directly compare the safety risks of giving the vaccine at bi rth versus later in early
childhood. She asked how many of the studies presented by the CDC applied specifically to
neonates and echoed earlier questions about follow -up and long -term safety data. She
emphasized the need for more robust long- term data, particularly for infants of hepatitis B -
negative mothers, where the risk of infection is low, to weigh risks and benefits thoroughly.
 Dr. Griffin addressed Dr. Stein’s earlier question about safety, noting that the CDC confirmed as
early as 2020 that no cases of hepatitis B transmission had been documented in school
settings, including elementary, middle, or high schools. She then referr ed to slide six, asking
about its source and what year it was from.

Dr. Langer responded that multiple reports are stating the vaccine was safe, published in 1994,
2002– 2004, 2012, and 2013.

Dr. Griffin followed up, noting that in 2012, the Institute of Medicine reviewed hepatitis B vaccine
safety studies and concluded that evidence was inadequate to rule out the possibility that
vaccination could lead to more than two dozen neurologic and aut oimmune disorders. She
asked how this statement could be reconciled with describing the vaccine as safe and effective.

29
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Wester added that, while the 2012 Institute of Medicine report stated there was insufficient
evidence to accept or reject a causal relationship, an extensive body of literature has emerged
over the past four decades. She noted that colleagues in the Im munization Safety Office would
provide additional data and are better positioned to respond in detail.

Dr. Hibbeln stated that the question before the committee is whether the first dose of the hepatitis B vaccine should be delayed until one month of age for infants of hepatitis B -negative
mothers. He said he was unclear if any safety or hazard data had been presented comparing
vaccination before versus after one month. He asked why one month was chosen as the time
point, and whether data exist showing a greater risk of adverse effects before or after that age.

Dr. Kulldorff noted that the current schedule recommends the second dose at one to two
months of age, so delaying the first dose until one month would coincide with or come after the
second dose. He suggested that the CDC is best suited to address the broader question of
safety.

Dr. Hibbeln reiterated that the committee is being asked to vote on whether the first dose should
be delayed until at least one month of age for infants of negative mothers. He wondered if data
show that vaccination before one month carries a greater risk of adverse effects than after one
month.
 Dr. Malone added by asking whether there is data on a gradient of adverse events by age post -
birth, rather than only at the one- month time point, and whether risk decreases over time.
Dr. Hibbeln agreed, emphasizing that if the committee is to vote on delaying the dose to one month, data are needed comparing adverse effects before and after that time.
 Dr. Malone asked whether one month represents a distinct point of higher or lower risk, or if risk
changes more gradually over time, and whether data is available to clarify this.

Dr. Kulldorff suggested the committee proceed to the safety presentation to address these
questions.
 Dr. Pebsworth raised concern about data showing that 12– 16% of women do not receive
prenatal care or hepatitis B screening. She questioned whether infants are being born in the
U.S. without the mother’s hepatitis B status known, noting that a rapid test (s tat titer) should be
able to provide results within one to two hours, which has important implications for infant care.
Dr. Kulldorff responded that while in principle maternal status should always be known, the
standard test typically takes one to three days, so results may not be available before delivery.

Dr. Pebsworth noted reports that a stat titer can provide results in one to two hours and asked if
this was accurate.
 Dr. Griffin, speaking as an obstetrician- gynecologist, confirmed that the screening test can
indeed be completed in under one hour, with results often available the same day. She added
that in the U.S., 98– 99% of women deliver in hospitals with laboratory capacity, and most
receive prenatal care. While approximately 7% of women lacked prenatal care in 2023
(according to the March of Dimes), hospitals routinely test for hepatitis B surface antigen at
delivery if prior results are unavailable, with results ty pically available within hours.

Dr. Levi asked whether informed consent discussions with mothers include the opportunity to
test at delivery, assuming such talks take place as part of the decision to vaccinate the infant.
30
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.
Dr. Griffin added that women typically remain in the hospital for at least 24 hours postpartum,
allowing time for confirmatory testing and administration of infant vaccinations and HBIG, if
needed. She reflected that this raises an important question: are we vaccinating all newborns on
day one to lower hepatitis B prevalence in high- risk populations, essentially asking babies to
solve an adult problem?
 Dr. Langer explained that while a rapid hepatitis B test can sometimes be completed within 30
minutes to an hour, this assumes an ideal situation. Factors such as births outside hospitals,
laboratory backlogs, or the need for confirmatory testing can cause delays in results. He noted
that vaccination within 12 hours can avoid these risks and ensure timely protection. He added
that there are no data showing harm from vaccinating at birth compared to one month, but there
are potential harms to delaying the dose, while the vaccination series would still be needed
regardless.

Dr. Kulldorff clarified that initial rapid testing can identify if a mother is negative within a short
time, while positive results require longer confirmatory testing.

Dr. Griffin agreed, noting that the purpose of screening is to quickly identify those at risk, which
allows for counseling and informed consent. She confirmed that in practice, results are available
within a few hours, certainly within the first day, while the patient is still in the hospital.
 Dr. Kulldorff added that for the committee’s decision, it is only necessary to know if the mother is negative. If the initial test is positive, the mother can be treated as positive without waiting for
confirmation.
 Dr. Griffin agreed.

Dr. Pollak noted that data suggest children not vaccinated in the perinatal period are much less
likely to return for vaccination later, with a hazard ratio of three. He emphasized that this
disproportionately affects single mothers, women of low socioeconomic status, persons of color,
and high- risk groups such as Alaskans and First Nations. He requested data from the CDC on
follow- up and vaccination completion among infants who were not vaccinated at birth, such as
those weighing under 2,000 grams or those  with contraindications.

Dr. Langer responded that there is an association between receiving the birth dose and
completing the vaccine series on time. Infants who do not receive the birth dose are less likely
to be vaccinated later.

Dr. Pagano asked whether this association is confounded by parental choice, noting that some
parents may refuse the birth dose and also decline later doses.
 Dr. Langer agreed that the association does not imply causation. Parents who accept the birth
dose are more likely to complete the series, but the underlying factor may be parental
willingness rather than the timing of the first dose.

Dr. Levi noted that Canada’s provinces have a wide range of hepatitis B vaccination policies,
with first doses given as early as two months or as late as 11– 12 years. He asked whether
outcomes differ by province and if delaying vaccination for infants of m others with negative test
results shows any impact on incidence.

31
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Meissner emphasized that targeting select groups for vaccination has historically been less
effective than broad recommendations. He noted the difficulty of identifying and vaccinating
high- risk groups such as IV drug users, sex workers, and people experiencing homelessness.
He added that hepatitis B vaccination at birth, followed by the recommended series, likely
provides lifelong protection, as even if antibodies wane, cellular immunity produces an
anamnestic response upon exposure. He argued that no data suggest that vaccination at two or
three months is safer than at birth, calling the vaccine extremely safe, with severe allergic
reactions occurring in approximately one in a million doses. He questioned what would be
gained by delaying the birth dose.
 Dr. Hibbeln asked for clarification that hepatitis B can be transmitted to infants from sources
other than the mother, noting that the virus survives on surfaces and can be spread by many
people.

Dr. Levi responded that he was not aware of any documented data showing children becoming
infected through such mechanisms, although he acknowledged that he could have missed
relevant studies.

Dr. Langer pointed out that during his presentation, he discussed  a study of U.S. -born children
of immigrant mothers who tested negative at birth found that 7– 11% later tested positive for
hepatitis B surface antigen, proving infections occurred postnatally. These children were too
young for sexual or injection drug exposures, and their mothers were confirmed negative, so
transmission had to occur through casual or household contact. He added that the virus can survive on indoor surfaces for at least seven days, suppo rting the likelihood of community or
household transmission.

Dr. Stein observed that the percentages cited for infections from non -maternal sources
represent attributable risk rather than raw incidence counts. She emphasized that while still
important, these numbers are not the same as direct incidence data.

Dr. Hibbeln responded that his concern was not about exact numbers but about the framing of
the committee’s vote, which divides infants only by maternal hepatitis B status. He argued that
infections can occur from other household or community sources, and therefore, relying solely
on maternal status is insufficient. He stated that the most prudent approach would be to
vaccinate as many children as possible to protect them broadly.
 Dr. Griffin noted that informed consent discussions and social history intake are part of medical
practice, where providers assess risk factors with patients.

Dr. Hibbeln countered that if roughly half of infected people are unaware of their status,
informed consent discussions cannot reliably identify risk.
 Dr. Griffin replied that physicians should still ask these questions and document the responses
in electronic medical records, which could eventually be analyzed using advanced tools.

Dr. Hibbeln responded that patients often cannot answer questions about their household
infection status if no one in the household has been tested.
 Dr. Griffin reiterated that risk assessment must start somewhere.

32
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Hibbeln concluded that if the goal is lifelong universal protection from a vaccine with very
few side effects, then limiting the recommendation based on maternal status alone is flawed,
since infection can occur from many sources throughout life.

Dr. Meissner emphasized that medicine is not precise, and the risk for hepatitis B cannot be
reliably determined through questioning alone, similar to HIV. He added that maternal testing is not perfect, with potential errors in transcription, assay perform ance, and distinguishing between
hepatitis B surface antigen and surface antibody. He concluded that no system will ever identify
all hepatitis B surface antigen– positive mothers at delivery with 100% accuracy.
 The ACIP chair , Dr. Kulldorff,  requested a review of the 2004 study by Garly and colleagues
titled Hepatitis B vaccination associated with higher female than male mortality in Guinea -
Bissau: an observational study . The review included an assessment of non- specific effects of
vaccination and findings from a rapid systematic review on mortality following hepatitis B
vaccination.

Non-specific effects are defined as vaccine effects beyond protection against the target
pathogen, possibly due to changes in the immune system. These differ from adverse, cross -
protective, or indirect downstream effects. Clinical manifestations may include all -cause
mortality, increased susceptibility to unrelated infections, or an increased risk of allergic and
autoimmune diseases. Live attenuated and non- live vaccines may differ in these effects.
 Garly and colleagues noted that while some studies have examined non- specific effects of
vaccines on all -cause mortality, few have assessed hepatitis B vaccination specifically. Their
study aimed to determine whether the hepatitis B vaccine was associated with sex -specific
differences in mortality. The study was conducted within a trial of a two- dose standard measles
vaccine in the Bandim Health Project surveillance system in Guinea- Bissau. Birth cohorts from
March 1994 through February 2000 were included. Children born from March 1996 through
February 1997 were eligible to receive a hepatitis B vaccine at 7.5, 9, and 10.5 months of age.
The product used was a human plasma- derived vaccine, which is not licensed in the U.S.  [This
raises questions about the applicability or relevance of the Garly et al. study to current U.S.
hepatitis B immunization recommendations.]

A Review of the Safety of Hepatitis B Birth Dose Vaccination
Dr. John Su (CDC/NCEZID)
Dr. John Su (CDC/NCEZID) reviewed the safety of hepatitis B birth dose vaccination. The ACIP
chair requested safety data on hepatitis B administration within 24 hours of birth from the CDC’s
Vaccine Safety Datalink (VSD) and the FDA’s Biologics Effectiveness and Safety System. The
request included mild and serious adverse events, all -cause morbidity and mortality, short - and
long- term safety, outcomes of predetermined concern, and data- mining results, with findings
reported both combined and stratified by s ex.
To address this, the CDC conducted a rapid systematic review of safety data on hepatitis B
vaccination within 24 hours of birth. The key question was the safety of the vaccine when
administered in the first 30 days of life. To capture a broad range of studies, the review included
all vaccines administered within 30 days, not just 24 hours. The search was performed on July
31, 2025, using PICO (ST) criteria, and databases searched included Medline, EMBASE,
CINAHL, and Cochrane.
Inclusion criteria were newborn infants receiving hepatitis B vaccine at 30 days or less,
randomized controlled trials, observational studies, case series with 10 or more patients, and
33
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  surveillance data. Outcomes included safety, adverse events, serious adverse events, and side
effects. Exclusion criteria included non- English articles, animal studies, populations not
receiving the vaccine within 30 days or less, case series with fewer than 10 patients, clinical trial protocols, conference abstracts or posters, proceedings, or journal titles beginning with a
number.
The search identified 1,916 studies; after removing duplicates, 1,90 7 remained. Title and
abstract screening excluded 1,678, and full -text review excluded another 158. Of the 71 studies
left, 20 either focused on the birth dose or reported results stratified by birth dose.
Among these, five defined birth dose as administration within 24 hours of birth, including one VSD study. Four, including another VSD study, used terms such as “at birth,” “birth dose,” or
“within 120 hours.” One study reported that 85% of infants received  hepatitis B on the day of
birth, with none vaccinated beyond 8 days. The remaining 11 studies allowed vaccination at any
time in the first month of life; although included in the systematic review provided to ACIP, they
were not discussed at the meeting.
Studies evaluated l ocal reactions. One randomized trial found 7.7% of infants experienced pain
with movement or pressure within 5 days of vaccination. Three studies reported pain or
soreness within 4 days for fewer than 10% of infants, with few severe cases. For injection site
redness, one trial reported none within 5 days, while three studies reported 8– 20% within 4
days, with no severe cases. For swelling, one trial reported a 7.7% rate within 5 days, while
three studies reported 0– 4% within 4 days, with no severe cases. One trial that evaluated local
reactions as a combined outcome found 2.8% of infants experienced a reaction within the first week.
Studies also evaluated systemic reactions. Four studies on fever after hepatitis B vaccination
within 24 hours of birth reported rates ranging from 0 to 5.6% during birth hospitalization up to
21 days after birth. Among three studies where vaccination occu rred within 0 –5 days of birth,
fever within 4 days of vaccination was reported for 0– 5.9% of newborns. Few cases were
severe.
For anorexia or decreased appetite, one randomized trial of vaccination within 24 hours of birth
reported no cases within 5 days of vaccination. In three studies where vaccination occurred
within 5 days of birth, anorexia, feeding issues, or decreased appe tite within 4 days of
vaccination were reported in 2.6– 16.5% of newborns, with few severe cases.
For diarrhea or vomiting, one randomized trial of vaccination within 24 hours of birth reported no
cases within 5 days of vaccination. Two additional studies where vaccination occurred within 5
days of birth found diarrhea or vomiting within 3 days of vacc ination in 8.1 –11.7% and 4.4–
22.3% of infants, respectively , with no severe cases .
For irritability or fussiness, one randomized trial of vaccination within 24 hours of birth reported
11.5% of infants affected within 5 days of vaccination. Across three other studies where
vaccination occurred within 5 days of birth, irritability, fussiness, or unusual crying within 4 days
of vaccination was reported in 1.5– 22.1% of infants. Few cases were severe.
No studies specifically evaluated sleep disturbance after vaccination within 24 hours of birth.
However, three studies where vaccination occurred within 5 days of birth reported drowsiness or
increased sleep within 4 days of vaccination in 5.1– 32.4% of inf ants, and restlessness or
reduced sleep within 3 days of vaccination in 16.9– 31.1% of infants. Few cases were severe.
A cohort study of vaccination within 24 hours of birth found no differences in care for allergic
reactions between vaccinated and unvaccinated newborns within 21 days of life. No additional
studies evaluated allergic reactions in infants vaccinated within 5 days of birth.
34
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  One study evaluated infections after hepatitis B vaccination within 24 hours of birth. In this
cohort study, vaccinated newborns were less likely to be evaluated for possible sepsis and less
likely to have a positive blood or cerebrospinal fluid culture. N o studies assessed infections
among newborns vaccinated within 5 days of birth.
Two studies examined other adverse events. In one cohort, hepatitis B vaccination within 24
hours of birth did not increase the risk of seizures or other neurologic disorders. In another cohort of preterm infants identified through Australia’s surveillance system, hepatitis B
vaccination appeared to have a slight protective effect against bronchopulmonary dysplasia. In
an additional cohort where vaccination was administered within 5 days of birth, one serious
adverse event was reported: a cough that require d hospitalization 37 days after vaccination,
which the investigators deemed unrelated.
One study evaluated all -cause mortality after hepatitis B vaccination within 24 hours of birth. In
a cohort of preterm infants in Australia, there were no differences in mortality within 3 months of
life between vaccinated and unvaccinated infants. Two studies assessed mortality after hepatitis
B vaccination within 8 days of birth. In one randomized trial, no deaths occurred during a 7-
month follow -up period among infants who received the hepatitis B vaccine within 4 days of
birth. In a large US cohort study including more than 350,000 live births between 1993 and 1998, 1,363 neonatal deaths within 29 days were identified. Of these, 72 (5%) occurred in
infants who received the hepatitis B vaccine at birth. No significant differences were observed
between vac cinated and unvaccinated newborns in rates of expected or unexpected deaths,
including deaths due to sudden infant death syndrome.
Limitations of this rapid systematic review include the small number of studies on hepatitis B
vaccination within 24 hours, inconsistent reporting of timing, and heterogeneous methods that
prevented meta- analysis. Most studies have focused only on short -term outcomes, such as
reactogenicity or mortality within 30 days, while long- term outcomes have not been captured.
Dr. Su concluded that the review found no increased risk for allergic reactions, mortality, sudden
infant death syndrome, seizures, or other neurologic disease. Compared to infants who did not
receive the birth dose, those who did had lower risks of invasi ve diagnostic procedures, positive
cultures, and bronchopulmonary dysplasia. Results on short -term reactogenicity varied across
studies.
Non-specific effects following hepatitis B vaccination
Dr. John Su (CDC/NCEZID)
Dr. John Su (CDC/NCEZID) shared data on non -specific effects following hepatitis B
vaccination. The ACIP chair requested that the Immunization Safety Office present the 2004
study by Garly and colleagues, “Hepatitis B vaccination associated with higher female than male
mortality in Guinea- Bissau : an observational study .” In addition, Dr. Su presented the results of
a rapid systematic review of non -specific effects (NSEs) of Hepatitis B vaccination, including
data on mortality after hepatitis B vaccination. NSEs are effects beyond protection against the
target pathogen, potentially  mediated by immune system changes; they are distinct from
adverse, cross -protective, or indirect effects , and may manifest as changes in all -cause
mortality, unrelated infections, or risk of allergic and autoimmune diseases. Live- attenuated and
non-live vaccines may differ in their NSEs.
The Garly 2004 study aimed to assess whether hepatitis B vaccination is associated with sex -
specific differences in mortality. It was conducted within a two- dose standard measles vaccine
trial embedded in the Bandim Health Project surveillance system in Guinea- Bissau. Birth
cohorts from March 1994 through February 2000 were enrolled. Children born from March 1996
35
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  to February 1997 were eligible for the hepatitis B vaccine at 7.5, 9, and 10.5 months of age. The
hepatitis B product used was a human plasma– derived vaccine not licensed for use in the U.S.
Dr. Su summarized three mortality comparisons. First, across birth cohorts, mortality at 7.5– 12
months was compared with mortality at 1.5– 7.5 months; overall, the rate ratio was 0.97, but in
the year when most children received the hepatitis B vaccine at 7.5 months, it was 1.62 (95%
CI, 1.09 –2.41). Second, among 5,441 children in the two-dose measles vaccine trial , the
mortality rate ratio at 7.5 –12 months was 1.81 (95% CI, 1.19– 2.75) for hepatitis B -vaccinated
children compared to unvaccinated children. Third, among measles -vaccinated children, the
female- to-male mortality rate ratio was 1.66 (95% CI 0.80– 3.45) through 12 months of age for
those who also received hepatitis B vaccine; through 24 months of age, the rate ratio was 2.20
(95% CI 1.07– 4.54) with both vaccines versus 0.96 (95% CI 0.70 –1.32) with measles vaccine
only. The study authors (Garly, et al.)  concluded these analyses suggest changes in mortality
patterns after hepatitis B vaccine introduction in a high- mortality setting, with a stronger eff ect
among females, raising the possibility of sex -differential non- specific effects.
These analyses were not planned when the trial was designed, and the study was not randomized, so unbiased comparisons over the same time period could not be ensured.
Hepatitis B vaccine was administered at 7.5, 9, and 10– 10.5 months in this study; therefo re, the
effects may differ when given at birth or alongside other vaccines, such as BCG. A higher
female- to-male mortality ratio could also reflect reduced male mortality.
A rapid systematic review was conducted to [address the question, “W hat are the non -specific
effects of hepatitis B -containing vaccines administered in childhood?”]  The review included
studies published through August 20, 2025, among infants and children up to six years of age
who received either a monovalent hepatitis B vaccine or a combined vaccine, compared with
any or no comparator. Outcomes included non -specific effects ; studies in any setting and of any
duration of follow up were included for review.
Inclusion criteria allowed for clinical trials, observational studies, surveillance reports, and
systematic reviews. Eligible populations included infants and children younger than seven years
of age who had received a hepatitis B vaccine, either alone or in combination. Included s tudies
evaluated outcomes related to non -specific effects. Exclusion criteria ruled out case reports and
case series, narrative reviews, animal studies, children older than seven years, adults, vaccines other than hepatitis B, an d studies assessing outcomes outside of non -specific effects.
A total of 2,068 studies were identified. After keyword screening, 237 remained; however, 221 were excluded during the title and abstract review. Sixteen full texts were reviewed, and eight
were excluded, resulting in eight studies included in the final review.
Of the eight included studies, four evaluated the hepatitis B vaccine as part of a pentavalent
vaccine and four evaluated the monovalent vaccine. Seven were cohort studies and one was a
nested case series. Six studies were conducted in low - and middle- income countries and two in
high- income countries. Four studies evaluated mortality, five assessed sex -differential mortality,
and one examined another non -specific effect.
Among the three studies that evaluated mortality, two cohort studies in high- income countries
found no association between hepatitis B vaccination and all -cause mortality. A cohort study
conducted in a low - to middle- income country found an increased risk of all -cause mortality
following vaccination.
Evidence regarding sex -specific mortality was inconsistent. One study observed both no
difference and an increase in the female- to-male mortality ratio. Another study suggested that
there is no difference in mortality by sex.
36
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  One cohort study in a high- income country evaluated cancer -related and cardiovascular -related
mortality and found no effect of hepatitis B vaccination on these outcomes.
Overall, there are few studies available to inform the non -specific effects of hepatitis B
vaccination in children. Studies in high- income countries found no association with all -cause
mortality, while one study in a low - to middle -income country suggested  an increased risk.
Evidence regarding sex -specific mortality was inconsistent.
Dr. Su concluded that non- specific effects may vary in settings with different background
mortality rates and infectious diseases burden . These effects may not be generalizable across
immunization programs and might also vary depending on the specific vaccine product used.
For example, Heppacine is not licensed for use in the United States, where the hepatitis B
vaccine is administered earlier and often in combination with other routine vaccines. The
biological, molecular, and immunologic mechanisms underlying non- specific effects are not fully
understood. In particular, the timing between vaccination and the onset of any non- specific
effect, as well as the duration of such effects, remains uncertain. The duration of a vaccine’s
non-specific effect may also be complicated by subsequent vaccinations received.
Discussion
Rick Haupt (Merck), head of the ID Vaccines Medical and Scientific Affairs group, shared a manufacturer statement. He referred to Dr. Langer’s presentation, which highlighted the
rationale and importance of routine newborn vaccination as a crucial public health strategy to
prevent chronic viral hepatitis and its severe long- term consequences. He noted that the risk of
developing chronic hepatitis B infection is strongly age- dependent, with up to 90% of infants
infected at birth progressing to chronic infect ion, which can lead to chronic liver disease and
liver cancer. Transmission may occur from an infected mother or through close contact with an
infected family member. He emphasized that the CDC has reported that one in two people is
unaware of their infect ion status. He stated that Merck’s Hep B vaccine, Mercivovax HB, was
first approved in the United States in 1986 and has been a foundation of hepatitis B prevention, with more than 330 million doses distributed between 1990 and 2019. Universal infant and
childhood vaccination for hepatitis B has resulted in a 99% decline in reported cases of acute
hepatitis B among children, adolescents, and young adults under 19 years of age. He concluded
that vaccines remain the best defense against many serious diseases,  with strong scientific
evidence supporting their use. He cautioned that reconsidering newborn hepatitis B vaccination
on the established schedule would pose a serious risk to the health of children and the public
and could lead to a resurgence of preventable infectious diseases.
Ayman Chit (Sanofi), head of the medical affairs department at Sanofi Vaccines in the United
States, shared a manufacturer statement. He emphasized that the company’s top priority is
ensuring access to safe and effective vaccines. He stated that administra tion of hepatitis B dose
early in life remains the most effective option for preventing hepatitis B infection in infants and children. He noted that scientific evidence strongly supports the safety of both hepatitis B
vaccines and combination vaccines that  include hepatitis B, and that these vaccines are
continuously monitored by manufacturers, public health agencies, and regulators before and after approval. He cautioned that changes to the hepatitis B infant schedule could disrupt
implementation and reduc e the benefits provided by combination vaccines. Combination
vaccines lessen the number of injections infants receive, improve provider workflow, and help
limit administration errors. If recommendations change for one component, providers will need
to stoc k both single- antigen and combination products, creating challenges with supply, storage,
handling, administration, and documentation. He warned that delaying the hepatitis B birth dose
puts infants at risk of infection and reduces families’ options to use combination vaccines. He
added that such a change would likely cause significant supply disruptions lasting a year or
37
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  longer due to the production lead time, affecting not only combination vaccines but also single-
antigen products such as Hib and polio. He concluded that maintaining current
recommendations for hepatitis B vaccination is critical to ensure infants remain protected early
in life, high -risk infants are not missed, and families continue to have access to widely available
combination vaccines that protect against multiple vaccine- preventable diseases.
Dr. Griffin stated that regarding the first presentation, she wanted to know how many of the
studies were based on thimerosal -containing vaccination.

Dr. Hause from the Immunization Safety Office stated that she did not have the number on hand
but could provide it after a brief review.

Dr. Griffin stated that she asked because there has not been a hepatitis B vaccine containing
thimerosal since 2001. She noted that she counted about five or six such studies and
questioned the rationale for including them. She asked if any of the studies were designed to
have safety as the primary endpoint, since many appeared to focus on immunogenicity.

Dr. Su stated that safety was part of the studies but deferred to colleagues for clarification on
whether safety was the primary endpoint.

Dr. Hause stated that several studies evaluated safety as the primary endpoint and that several
randomized controlled trials also included safety as a secondary endpoint.
 Dr. Griffin asked how many studies were specifically designed with safety as the outcome.

Dr. Hause stated that three studies specifically examined safety as an outcome.
 Dr. Griffin clarified that this meant three out of twenty studies and requested to go back to slide
23 from the first presentation.

Dr. Hause clarified that three out of nine studies were presented in the slides.

Dr. Griffin thanked her and requested that slide 23 be pulled up, noting it was a summary slide.
She inquired about the commentary on bronchopulmonary dysplasia, pointing out that she had
found one article, Morgan et al. (2025), and questioned whether that  was the only study used in
the summary.

Dr. Hause confirmed that it was.

Dr. Griffin expressed concern, stating that the authors of that study declared seven significant
limitations. She highlighted the inability to control for confounding factors, including infections
and respiratory support, and noted that clinician perception of newborn stability could also
influence vaccination decisions. She emphasized that withholding vaccination in unwell infants
could confound results and underestimate risks. She then asked if there were any other studies
showing findings related to bronchopulmonary dysplasia.

Dr. Hause stated that the study in question was included because it met the criteria for
systematic review. She noted that no other studies identified in the review met the criteria with
bronchopulmonary dysplasia as the outcome.

38
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Pebsworth referred to slide 15 from the first presentation, which evaluated systemic
reactions such as irritability, fussiness, or crying, noting rates of 20– 22% among participants.
She stated that these rates seemed very high, particularly since they may be early symptoms of
neurologic problems requiring long- term follow -up, which is lacking in the available data. She
commented on the Institute of Medicine (IOM) reports, clarifying that the IOM did not conclude
that the hepatitis B vaccine was safe but  instead reviewed multiple conditions and assessed the
weight of epidemiologic evidence, mechanistic evidence, and causality conclusions. She noted
that the IOM reviewed three reports on hepatitis B between 1994 and 2012 and concluded that
the evidence was  inadequate to accept or reject a causal relationship between the hepatitis B
vaccine and conditions such as encephalitis and encephalopathy. Additionally, the IOM found that of 26 conditions reviewed, this same conclusion applied to at least 24 of them. S he listed
several of the conditions considered in the IOM report, including encephalitis, encephalopathy,
seizures, acute disseminated encephalomyelitis, transverse myelitis, optic neuritis,
neuromyelitis Optica, multiple sclerosis onset and relapse, Guill ain-Barré syndrome, chronic
inflammatory demyelinating polyneuropathy, lupus, vasculitis, polyarteritis nodosa, psoriatic
arthritis, and reactive arthritis, emphasizing that the IOM conclusions indicated uncertainty
rather than confirmation of safety. She also referenced a 2024 systematic review on the safety
of hepatitis B vaccines in preterm infants, noting that it found no publications on the timing of the
birth dose and adverse events, and that reporting was limited to short -term outcomes,
highlighting that research on the safety of hepatitis B vaccination in preterm infants within seven
days of birth, especially regarding long- term morbidity, is lacking. She further referenced a 2016
mouse model study showing that neonatal hepatitis B vaccination impair ed behavior and
neurogenesis in early adulthood, with the conclusion that vaccination impaired hippocampal LTP and neurogenesis and that the possible mechanism involved alterations in the brain
neuroimmune milieu from a systemic TH2 bias. She concluded that there are gaps in knowledge
about the effects of hepatitis B vaccination on very young infants and stated that concluding the vaccine is safe may be premature.

Dr. Levi stated that the Garly paper was one of the most well -done examples of a natural
randomized experiment. He recalled that children vaccinated between seven and a half months
and 12 months showed almost 80% higher mortality compared to other cohorts.  He asked why
this result was not discussed and whether it was because the focus was on earlier age groups.

Dr. Su asked if Dr. Levi was referring to the Garly paper and clarified that he was reviewing his
slides. [This finding was presented on slide nine. In comparison two, a mong children enrolled in
the measles vaccine trial, compared with HBV -unvaccinated children, the mortality rate ratio for
children 7.5 -12 months of age from the HBV -vaccinated cohort was 1.81 (95% CI 1.19, 2.75). ]

Dr. Kulldorff stated that while Dr. Su was reviewing, the discussion could move to Dr. Milhoan.

Dr. Milhoan stated that the neonatal period is a very sacred time for intervention and that
medical decisions at this stage must be approached with caution, as any changes in the baby’s
condition lead to invasive evaluations and treatments. He explained that risks are higher for
procedures such as anesthesia and surgery in newborns, particularly premature infants. He
emphasized that while public health prioritizes populations, it does not always prioritize
individual patients, and decisions for the most vul nerable must be made with utmost caution. He
questioned whether seroconversion rates had been evaluated starting at two months rather than at birth, pointing out that while seroconversion occurs at a rate of 26% at birth, higher levels are
achieved after s ubsequent doses, with approximately 95% after the third dose. He suggested
that beginning vaccination later might reduce the number of doses required and decrease risk,
39
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  since every injection carries some risk. He asked whether T -cell immunity, which may be more
robust early in life, had been considered as part of the vaccine response.

Dr. Levi added that seroconversion rates were 25% after the first dose, 63% after the second
dose, and 95% after the third dose.

Dr. Milhoan stated that if vaccination began at two months and continued at six months, the
seroconversion rate should be examined to see whether earlier vaccination unnecessarily adds
doses. He clarified that he was not advocating against vaccination but instead suggesting that
risks could be reduced if the schedule were reevaluated. He also referred to slide 23, which
summarized death outcomes, stating that rather than showing a positive effect of hepatitis B
vaccination, the data reflected selection bias : healthier children were more likely to be
vaccinated early, leading to more favorable outcomes unrelated to the vaccine. He noted that
this reflected selection rather than a true protective effect.

Dr. Kulldorff added that this phenomenon is called “healthy vaccination.”
 Dr. Milhoan continued by noting that while outcomes reported included allergic reactions and all -
cause mortality, other important outcomes were missing. He asked whether data were available
on whether infants required advanced care or were coded.
 Dr. Su stated that he did not have that information and referred to the investigators of the paper.

Dr. Blackburn asked how the language was decided to recommend vaccination at one month
rather than two months, noting that most other countries recommend delaying for hepatitis B -
negative mothers. She stated that while she could see justification for this approach, she was
concerned when reviewing safety data about the risks of fever and poor feeding. She explained
that any fever in a newborn under 28 days is considered a medical emergency and typically
prompts a full sepsis workup, spinal tap, hospitalizat ion, and empiric IV antibiotics. She added
that, as a parent with firsthand experience, early feeding is essential to successful
breastfeeding, and a decreased appetite in the early days of life can have a significant impact.
She emphasized that these risk s should be taken into consideration when weighing the benefits
and harms.

Dr. Kulldorff  responded that the decision was related to the fact that the second dose in the U.S.
is recommended between one and two months of age, and he noted that he had been personally involved in discussions about the recommendation with CDC staff.

Dr. Malone stated that while concerns about irritability, fever, and poor feeding may or may not
be indicators of neurological problems, it is important not to base votes or recommendations on
speculation. He emphasized that decisions should be based on da ta reflecting concrete risks or
benefits, rather than hypothetical clinical outcomes for which there is no evidence. He referenced the IOM findings, noting that although neurological outcomes had been considered,
there was no evidence to make a causal link  either for or against such conditions. He concluded
that the committee should not extend beyond the data when making determinations.
 Dr. Meissner stated that there is no association or lack of association between the hepatitis B
vaccine and bronchopulmonary dysplasia (BPD). He explained that BPD occurs in preterm
babies who are typically more than 10 weeks early, weigh less than two pounds, and are often
mechanically ventilated. He emphasized that the condition results from barotrauma or trauma
associated with mechanical ventilation, making it biologically implausible for the hepatitis B
40
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  vaccine to have any relationship with BPD, and he advised not placing too much concern there.
He then referred to the Garly study and asked for clarification, noting that Dr. Su had given
excellent presentations, and inquiring whether the vaccine in that s tudy was a human plasma–
derived hepatitis B vaccine.

Dr. Su stated that the Garly paper involved a plasma- derived hepatitis B vaccine.

Dr. Meissner explained that the original hepatitis B vaccine was produced from the plasma of
people with chronic hepatitis B, which was then inactivated by heat or chemical treatment to
prevent infection before being concentrated. He emphasized that this v accine was very different
from the current vaccine, which is made using cloned hepatitis B surface antigen in yeast,
resulting in a pure and well -defined product. He stated that the vaccine used in the Garly study
was not the same as the modern vaccine and  therefore should not be emphasized in current
discussions. He further noted that changing the recommendation for neonatal administration of
the hepatitis B vaccine would increase the risk of harm without evidence of benefit, as fewer
children would comple te the full hepatitis B vaccine series if initiation were delayed. He noted
that beginning vaccination in the hospital ensures that at least the first dose is administered. He stressed that there is no evidence to suggest that the vaccine becomes less safe  over time, that
it is extremely safe and pure, and that changing the recommendation could create unjustified
public doubts. He concluded that there is no evidence of harm from administering the neonatal
vaccine, either from presentations or from his review of the literature and expressed concern
about changing the recommendation.

Dr. Malone stated that he agreed with Dr. Meissner that the BPD signal was artifactual. He
noted that the reported improvement in risk of BPD in the paper likely reflects healthy vaccine
bias or reporting bias. He concurred that the Garly study involved the historic plasma -derived
vaccine, which was associated with adverse events not relevant to the modern product. He
noted that the question of changing recommendations also raised moral and ethical
considerations. He added that what he had not heard was clear data on the risks to premature
infants, and he asked for clarification on whether there are differences in safety, effectiveness,
immunogenicity, or seroconversion between premature infants and healthy newborns.
 Dr. Su responded that he could speak about the safety aspects, noting that the data were
limited to the studies that met the inclusion criteria. He stated that a few of those studies
addressed adverse events in premature infants, but deferred to other expe rts in the room for
further knowledge on that topic.
Dr. Hause stated that only one study met the criteria for the systematic review that looked at
premature infants, which was the Morgan study with the outcome of bronchopulmonary
dysplasia. She added that only one study specifically listed the use of a thim erosal -containing
hepatitis B vaccine.

Dr. Malone stated that, based on the discussion, there appeared to be insufficient data to
assess safety, immunogenicity, and seroconversion in premature infants, and he asked for
confirmation.

Dr. Langer responded that under the current recommendation, newborns weighing less than
2,000 grams who are born to hepatitis B -negative mothers should not be vaccinated at birth. He
clarified that the recommendation is to wait for one month.
 Dr. Milhoan asked whether the one month referred to gestational age or corrected age.
41
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.
Dr. Langer stated that he would defer to colleagues on that detail.
 Dr. Meissner stated that the recommendation is to wait until one month of age or until discharge
from the neonatal unit to home.

Dr. Kulldorff confirmed that this was correct.

Dr. Stein stated that her question concerned the extensive data provided in the summary
document, which included many detailed study summaries. She asked for clarification on what
is meant by “low confidence.”

Dr. Hause explained that each study was reviewed for risk of bias and graded using
standardized tools for systematic review. She stated that results varied by study, particularly in
relation to study design, and that details could be provided to the commit tee after the meeting.

Dr. Stein added that several studies had shown potential long- term risks, but that bias might
influence these findings, and she had not reviewed them in detail.

Dr. Hause stated that there are studies examining long- term outcomes in the larger systematic
review. However , they were not included in the presentation because they did not assess
hepatitis B doses given within the first 24 hours of life, which was the specific request of ACIP.
She noted that those studies could be provided to the committee separately.

Dr. Middleman asked two questions. First, she asked what problem exists in the current
schedule that prompted the discussion, noting that the hepatitis B immunization schedule has been highly successful, with a favorable benefit -to-risk ratio. She emphasiz ed that while there
are always risks and benefits to weigh, risk -based approaches to vaccination have historically
not been effective across multiple vaccines. She expressed uncertainty about what specific
issue had led to reopening the discussion. Second,  she commented on the exclusion of liaison
members from working groups, noting that liaison members bring extensive knowledge and
represent patients. She emphasized that their perspectives on issues such as adjuvants or
neonatal vaccination thresholds add value to vaccine recommendations. She asked how liaison
members might be included again to contribute on behalf of their patients and their expertise.
 Dr. Kulldorff responded to the second question, explaining that the exclusion of liaison members
from working groups was a CDC -wide Federal Advisory Committee Act (FACA) policy, which
was outside the control of ACIP. He stated that in the past, ACIP had no t been following this
requirement, and the change was necessary to align with FACA rules. He agreed that liaison member input is valuable, but clarified that outside experts, including those affiliated with
organizations represented by liaison members, are included in working groups. He explained
that these experts serve as individuals rather than representatives of their organizations. He concluded that while outside expertise is incorporated, ACIP must comply with FACA policy
regarding liaison members. Regarding the first question, he invited Dr. Levi to respond.

Dr. Levi shared two personal experiences. He stated that he had received the hepatitis B
vaccine as an adult before traveling to high- risk areas, and that all six of his children received
the vaccine on the first day of life without prior discussion or inf ormed consent. He suggested
that this illustrates how often informed consent may not occur for this vaccine. He expressed
concern about the frequent claim that “there is no evidence of harm,” emphasizing that the
relevant question is whether there is evidence of no harm, particularly for a vaccine
42
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  administered on the first day of life to healthy infants. He argued that the risk of not vaccinating
on the first day of life is likely negligible during the first several months or even years. He
questioned why there have been no large, long- term randomiz ed clinical trials (RCTs) to resolve
the debate about safety, stating that the lack of such trials reflects broader problems with the
medical system and vaccine research. He reiterated his belief that the hepatitis B vaccine is life -
saving and essential fo r high- risk infants and adults. Still, he stated that arguing from weak
evidence undermines trust and is not a scientific approach. He described the absence of long-term RCTs as the “elephant in the room.”

Dr. Fryhofer, a general internal medicine physician in full -time practice and the American
Medical Association (AMA) liaison. She disclosed that she had received the hepatitis B vaccine
as a medical student after rotating through a hepatitis ward, where she saw severely ill patients.
She stated she was thankful the vaccine exists. She explained that the hepatitis B virus
primarily affects the liver and can cause chronic infection, cirrhosis, liver cancer, and death. She
noted that the virus can be transmitt ed in utero and through bloodborne routes, and that when
transmission occurs in utero, 90% of infants remain chronically infected. She highlighted that
administering the hepatitis B vaccine at birth has nearly eliminated perinatal hepatitis B, with
only 13 cases reported in 2022. She emphasized that the birth dose is safe and effective and
stated that the AMA strongly urges ACIP to maintain the recommendation for newborn
vaccination.
 Dr. Munoz, a pediatric infectious diseases physician specializing in transplant infectious
diseases at an institution that performs the largest number of pediatric liver transplants in the country, and a clinician- investigator with many years of vaccine re search experience, asked why
the hepatitis B vaccine recommendation is under review and whether there is a specific reason
for considering a change. She emphasized that the data presented show significant declines in
hepatitis B incidence and long- term con sequences due to vaccination, both in children and
adults, and that this progress is directly attributable to vaccination. She noted that the vaccine
strategy is safe, effective, and widely implemented globally, with U.S. data suggesting that
hepatitis B c ould be eliminated through continued vaccination. She emphasized that risk -based
strategies are imperfect due to potential false- negative tests, inadequate prenatal care, limited
access, and gaps in understanding vaccine benefits. She warned that changing the
recommendation could reintroduce vertical transmission or leave adolescents unprotected,
resulting in severe disease. She concluded that the vaccine is very safe, that those at greatest
risk would be most affected by changes. She urged the committee to maintain the current
recommendation to protect both individuals and the broader public, especially the most vulnerable.

Dr. Paulsen, a liaison with the Pediatric Infectious Disease Society, stated that he agreed with
the concerns raised by ACIP members regarding the protection of children in the newborn
period, which he described as a sensitive time. He noted that the hepat itis B birth dose
ultimately comes down to weighing risks and benefits. He emphasized that CDC presentations consistently showed the risks to be low and that the data specifically focused on the infant birth
dose. He highlighted that fever in infants often  prompts a sepsis workup, including a lumbar
puncture, but that CDC data showed the risk of requiring such a workup was lower in infants
who received the hepatitis B vaccine within 24 hours. He concluded that the benefit is avoiding
a lifelong, chronic, vaccine -preventable infection. While in an ideal world, all maternal infections
would be known and properly managed, public policy must be based on what protects the population broadly. He urged ACIP to continue preventing infection in children rather than
treating hepatitis B as an adult problem.

43
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Buchanan, representing the National Association of Pediatric Nurse Practitioners, stated that
she wanted to echo and reiterate the safety of the vaccine. She shared her personal experience
caring for many children and administering the hepatitis B vacc ine in clinics, emphasizing that
under her care, no child had been harmed by the vaccine. She added that while members were
sharing personal accounts, she also wanted to raise the broader question many were asking:
why the vaccine’s safety is being reconsi dered now, given its well -established record of safety
over several decades.

Dr. Hayes, representing the American College of Nurse Midwives, stated that in most facilities,
when a woman in labor signs the consent form, it includes consent for the hepatitis B vaccine
dose. She explained that in her experience, the process functions as a universal consent, with
the option for refusal, meaning parents can decline the hepatitis B vaccine if they choose.

Dr. Jshlay, a family physician who provides prenatal care, stated that hepatitis B screening is
often done early in pregnancy, but that risk can change over time. She noted that the growing
uninsured population, including those losing commercial or Medicai d coverage, increases the
likelihood of patients presenting without prenatal care at delivery, making it difficult to obtain timely test results. She added that many patients do not disclose risk information due to
embarrassment or stigma. She emphasized t hat if vaccination approaches differ based on risk,
mothers may be stigmatized; universal vaccination avoids this by ensuring all families are treated equally, which supports equity in care.
 Dr. Hopkins stated that his greatest concerns related to equity and lack of knowledge. He noted that about 50% of adults in the population, including those presenting for delivery, do not know
their hepatitis B status, and congenital hepatitis B infections  continue to occur. He stated that
removing the birth dose would increase population risk and that equity must remain central in the evidence -to-recommendation framework. He added that while additional long- term data may
be needed, as Dr. Levi suggested, i t would not make sense to remove a successful intervention
while waiting for such data. He concluded that decisions should be made with care and based
on the full body of evidence, rather than being rushed.

Dr. Malone stated that the central question repeatedly raised, particularly by liaison
representatives , is why the issue of deferring the hepatitis B birth dose to one month is being
considered now, given that no clear safety signal has been detected. He suggested that the
timing appears to be less tied to scientific evidence and more to public trust, noti ng that a
significant portion of the U.S. population has concerns about vaccine policy, mandates, and the administration of the hepatitis B vaccine at bir th without meaningful informed consent. He
observed that the birth setting is often stressful and overwhelming, making it difficult for parents
to process information and provide truly informed consent, and that some parents feel the
vaccine is administered unilaterally by medical professionals. He linked these concerns to
broader declines in public trust in vaccines and public health following the COVID -19 pandemic.
He referenced Sweden as an example where, despite the absence of vaccine mandates and a hepatitis B birth dose, vaccine uptake is high and infectious disease outcomes are strong,
attributing this to greater public trust in Swedish public health. He concluded that the issue
before ACIP is not driven by a safety signal but by public discomfort and  mistrust, and that while
data presented may provide reassurance, many concerns will likely persist. He clarified that he
had no direct communication with CDC or HHS leadership on this issue and was offering his
perspective based on public opinion trends.

44
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Proposed recommendations and discussion
Dr. Martin Kulldorff (ACIP Chair)
Proposed Recommendation #1:
 All pregnant women should be tested for hepatitis B infection.
Proposed Recommendation #2:
 The pediatric vaccine schedule should be updated to reflect the following change:
 If a mother tests HBsAG -negative:
-The first dose of the Hepatitis B vaccine is not given until the child is at least one
month old.
-Infants may receive a dose of Hepatitis B vaccine before one month, according
to individual based decision- making.*
*Also referred to as shared clinical decision- making.
Dr. Kulldorff clarified that if parents choose to have the first dose administered on day one or at
any time before one month, even if the mother tests negative, the dose will be covered by CMS,
Medicare, Medicaid, and other health insurance providers.
VFC Resolution Update: Hepatitis B Vaccines
Jeanne Santoli (CDC/NCIRD)
Jeanne Santoli (CDC/NCIRD) presented on the resolution with all revisions from the previously
approved resolution shown in red. The purpose of the update is to update the Recommended
Vaccination Schedule and Intervals section to align with the proposed  recommendations
regarding the hepatitis B birth dose  under discussion today by ACIP . She reviewed the changes
to the infant vaccination table, clarifying that for infants weighing at least 2,000 grams and born
to mothers who are hepatitis B surface antigen– negative, the timing of the first dose was  revised
to 1-2 months and the second dose was adjusted to 3-4 months  for infants receiving single
antigen vaccine. For infants weighing less than 2,000 grams and born to hepatitis B surface
antigen– negative mothers, the timing was the same. She explained a  revised footnote stating
that only the single- antigen hepatitis B vaccine can be given at less than or equal to six weeks
of age, replacing prior language that referred to birth. She highlighted two new footnotes
reflecting individual -based or shared clinical decision- making for both ≥2,000- gram and <2,000-
gram infants with hepatitis B surface antigen– negative mothers, allowing for one dose to be
administered before one month  of age. She confirmed that there were no changes to children’s
vaccination schedule table , related table notes, interrupted schedules, minimum dosing
intervals, revaccination guidance, recommended dosage, contraindications, or precautions. She closed by noting the standard clause that new guidance published within six months would be
incorporated by reference, which was also unchanged.
Votes
Discussion
Dr. Hayes suggested revising the wording slightly to specify the antigen test rather than the
antibody test, to provide clearer guidance for clinicians.
Dr. Kulldorff agreed that this was a good suggestion and stated that CDC colleagues could refine the exact language to ensure the proper test was clearly identified.

Vote: Hepatitis B Vaccine Vote #1
Dr. Martin Kulldorff (ACIP Chair)  read the following proposed ACIP voting language for the
vaccine into the record:
45
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.
All pregnant women should be tested for hepatitis B infection.

Motion/Vote: Hepatitis B  Vaccine

Dr. Levi motioned to approve the recommended voting language, stating,  “All pregnant women
should be tested for hepatitis B infection. ” Dr. Griffin seconded the motion. No COIs were
declared. The motion carried with 12 votes in favor, 0 votes opposed, and 0 abstentions. The
disposition of the vote was as follows:

    12 Favored:  Malone, Hibbeln, Pagano, Milhoan, Blackburn, Griffin, Stein, Pollak,
Pebsworth, Levi, Meissner, Kulldorff
    0 Opposed:
    0 Abstained:

Dr. Pebsworth stated that after reviewing the CDC’s presentation, specifically slide 18 on the
global distribution of vaccination policies, she noted that in 26 countries, the first dose of the
hepatitis B vaccine is given to infants born to hepatitis B surface antigen– negative mothers at
two or three months of age. She explained that this included most of Europe, listing England,
France, Spain, Germany, Ireland, Norway, Denmark, Sweden, and Iceland. She pointed out that
the CDC had also reported variable r ates of reactogenicity within the first week of life, with data
showing systemic reactions among vaccinated infants. According to the data presented, up to
5% developed a fever, 32% were drowsy or sleeping, 3% had reactions categorized as severe,
and irrit ability, fussiness, or crying was reported for 11% within the first 24 hours and 22% within
the first five days. She emphasized that these were not trivial reactions and could affect up to one-third of births. She referenced the 2016 Yang study, which repo rted that hepatitis B
vaccination impaired behavior and neurogenesis, and a 2013 study by Celich, published in the
European Journal of Pediatrics, which found that 30% of infants developed significant elevations
in C- reactive protein without clinical signs  of sepsis and with negative blood cultures. She
explained that this indicated a robust inflammatory response occurring during a critical window of neurodevelopment, including neurogenesis and synaptic development. She concluded that,
given these findings and CDC data on systemic adverse reactions, the committee should
exercise caution and consider adopting a more prudent vaccination policy, similar to that of
most European countries, where low -risk newborns are not vaccinated on the first day of life
and v accination is typically delayed until two to three months.
 Dr. Malone stated that there were differences between what was presented and what was
published regarding the findings of the Institute of Medicine. He explained that, in his
interpretation, the IOM report indicated that for the 22 most claimed serious har ms, all but one
could not be assessed because studies had not been conducted to determine whether the
vaccine caused harm or not. He argued that interpreting this absence of data as evidence of
safety was misleading. He emphasized that case reports and cas e series suggest potential
harm, and that the IOM report did not conclude safety but rather acknowledged a lack of data.
He stated that for interventions in pregnancy and newborns, the burden must be to demonstrate
safety, not to assume safety until proven  otherwise, and he disagreed with the interpretation that
the absence of data implies the product is safe.

Dr. Hibbeln stated that he is a strong advocate for clinical decision- making but noted that the
wording of the question was logically inconsistent. He explained that the language said the dose
should not be given until one month, but also allowed for clini cal decision- making, which
46
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  contradicts the prohibition. He suggested modifying the wording to state that the first dose of
hepatitis B is not given until the child is one month old, except in cases where clinical decision-
making dictates otherwise, which would resolve the inconsistency.

Dr. Kulldorff asked whether changing the wording to “not recommended” would address the
concern.

Dr. Hibbeln responded that the phrasing still created conflict, as it both prohibited and allowed
administration. He reiterated that the language should specify that the vaccine is not
administered until one month, except in cases where a clinical decision is made.

Dr. Pollak raised a point of order, noting that the committee was debating language without a
motion on the floor. He reminded members of Robert’s Rules of Order, explaining that a motion
must be made before discussion, after which debate can occur. Then a  vote should be taken to
either accept or reject the proposal.

Dr. Malone moved to indefinitely postpone the question, noting uncertainty around safety,
effectiveness, and timing.

Dr. Pollak motioned to table, and Dr. Malone seconded.
 Vote: To table the Hepatitis B Vaccine Vote #2

Motion/Vote: Hepatitis B Vaccine

Dr. Pollak motioned to table the second vote on the Hepatitis B Vaccine. Dr. Malone seconded
the motion. No COIs were declared. The motion carried with 11 votes in favor, 1 vote opposed,
and 0 abstentions. The disposition of the vote was as follows:

    11 Favored:  Levi, Pebsworth, Hibbeln, Pollak, Griffin, Stein, Blackburn, Milhoan, Pagano,
Malone, Meissner
    1 Opposed:   Kulldorff
    0 Abstained:

Discussion
Dr. Meissner, responding to Dr. Malone’s earlier comments, stated that it is challenging to prove
the absence of harm and that such a goal is not practical. He emphasized that extensive
experience has been accumulated from administering the vaccine within the first 12 to 24 hours
of life, and that the concerns raised about irritability or restlessness are not objective measures
for assessing safety. He noted that since the motion to table had passed, there would be no
votes on the hepatitis B vaccine during this meeting.
 Dr. Stein cautioned against making absolute statements such as declaring the vaccine entirely
safe or entirely unsafe. She emphasized that the perception of safety often depends on the
perspectives of parents and children. She advised that the committee ca refully consider the
broader literature and patient experiences before reaching a conclusion.

Dr. Meissner responded that no vaccine is 100% safe or 100% effective. He stressed that
providers must weigh whether the benefits of protection outweigh possible side effects for each
47
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  patient. He concluded that, overall, the benefits of the newborn hepatitis B vaccine clearly
outweigh any potential adverse effects.
 Dr. Munoz stated that she was pleased with the decision to table the vote. She emphasized that
there have been 30 years of progress in preventing hepatitis B disease and related cancers,
and that the concerns raised about safety were based only on case reports and anecdotes rather than substantial evidence. She urged the committee to use proper processes to address
potential concerns, including requesting additional studies if needed. She argued that
dismissing a successful program would be more harmful than beneficial, given the data
presented. She also commented on the previous vote, noting that hepatitis B testing is already a
routine standard of care in prenatal and obstetric practice, and she asked what the committee’s
plan would be regarding that motion.

Dr. Kulldorff responded that hepatitis B testing is currently conducted in about 86– 87% of
pregnant women, but the goal should be to move closer to 100%.

Dr. Hopkins stated that if the issue of hepatitis B birth dose is revisited, it should undergo a full
review by a work group, including the complete evidence- to-recommendations framework, with
particular attention to the domains of equity and practical implementation.

Dr. Goldman echoed Dr. Hopkins’ comments and asked the chair to explain what process would
be used in the future to review evidence. He emphasized the importance of transparency about
whether the committee would continue to use the evidence- to-recommendati ons framework and
the GRADE process that work groups have traditionally used to evaluate trial power, quality,
bias, and conflicts of interest. He noted that recent discussions had not gone through the work
group process and stated that the public should b e aware of how future evidence will be vetted.
He commended the committee for tabling the vote to allow further discussion but requested
clarification on future methodology.

Dr. Kulldorff stated that he hoped the committee could return to the issue at a future meeting
and acknowledged that he could not provide a detailed response at that time.
 Dr. Middleman stated that the concerns raised were not limited to hepatitis B but reflected
broader issues that had been discussed across the committee. She emphasized that no
intervention is without risk, noting that even common treatments, such as Tylenol, amoxicillin, or
chemotherapy drugs, carry some level of risk, as does everyday activity, such as walking across
the street. She explained that the committee’s scientific responsibility is to determine whether
the benefits outweigh the risks. She urged m embers to avoid being distracted by isolated
studies and to rely on systematic approaches such as the GRADE framework or the evidence -
to-recommendations process to evaluate risks and benefits. She emphasized that the consistent
use of these methods is cruc ial for all vaccine decisions and that some concerns arose from
their absence in recent deliberations.

Dr. Levi stated that while he appreciated the emphasis on scientific methods, he was puzzled
that many of those advocating for rigorous approaches spoke with great confidence despite the
absence of gold- standard, long- term randomized clinical trials agains t a placebo. He noted that
such trials do not exist for this intervention and argued that if the committee seeks to uphold scientific rigor, it should do so consistently. He cautioned that confident statements about
vaccines being “safe and effective” were  being made without the highest standard of evidence
and encouraged members to show greater humility and acknowledge the limitations in the
available data.
48
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Kulldorff reminded the committee that the motion had been tabled. He encouraged those still
wishing to comment to bring their remarks forward if the issue is returned at a future meeting.

Dr. Goldman stated that, as Dr. Levi had mentioned, the committee needs gold- standard
evidence to guide decisions. He agreed that this is the role of the work groups and emphasized that the public should be adequately informed about the processes used to vet and discuss future vaccines. He emphasized that the evidence- to-recommendations framework was
established to establish a consistent standard for evaluating vaccines, but noted that it had not been applied in recent deliberations. He urged the committee to clearly communicate how
vaccine decisions will be analyzed in the future so the public can maintain trust, faith, and
confidence in the committee’s work.
Dr. Kulldorff responded that Dr. Goldman had already raised this comment previously and that
he had addressed it at that time.

PUBLIC C OMMENT
 The floor was opened for public comment on September 18, 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 -0454. Visit regulations.gov  for access to read the comments received.

Ms. Anu Hosangadi
Hepatitis B Foundation

Ms. Hosangadi  spoke on behalf of the Hepatitis B Foundation, emphasizing the long-
established safety and efficacy of the hepatitis B vaccine. She noted that since 1982, over a
billion doses have been administered worldwide with no new or unexpected safety concerns
identified through decades of surveillance and studies. She cited multiple CDC and Vaccine
Safety Datalink reviews confirming the vaccine’s strong safety record, including studies in
newborns and infants showing no increase in adverse outcomes. She highlighted the vaccine’s
effectiveness in providing long- term protection, its safety among pregnant women and
individuals with HIV, and the global data supporting continued universal birth- dose
administration. Ms. Hosangadi concluded by affirming that maintaining the universal hepatitis B
birth dose is a proven, safe, and lifesaving intervention.
 Samantha Sears,
National Consumers League
Ms. Sears, representing the National Consumers League, underscored the importance of ACIP
grounding its recommendations in medical science, particularly amid rising public distrust and
declining vaccination rates. She urged the committee to preserve the integrity of the U.S.
immunization system and to combat misinformation through clear,  consistent communication.
Ms. Sears expressed concern about potential changes to the childhood vaccine schedule,
warning that altering established recommendations could create confusion, reduce access, and
impose financial burdens on families. She stressed the need for alignment between ACIP, the
American Medical Association, and the American Academy of Pediatrics to avoid contradictory
messaging and safeguard children’s health.
49
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.
Dr. Rita Isabel Lechuga, MD, MPH
NASTAD

Dr. Lechuga, director of the hepatitis team at NASTAD, discussed the public health benefits of
universal infant hepatitis B vaccination. She traced the policy’s origins to ACIP’s 1991 recommendation, which led to a sharp decline in childhood hepatitis B cases by replacing failing
selective vaccination strategies . She noted that universal vaccination has been both cost -
effective and lifesaving , reducing perinatal transmission from tens of thousands of annual cases
to fewer than 1,000  today. Dr. Lechuga desc ribed hepatitis B as one of the first “anti -cancer”
vaccines due to its ability to prevent hepatitis D and liver cancer. She concluded by expressing hope that continued adherence to the universal birth- dose policy will lead the U.S. to eliminate
perinatal hepatitis B transmission.

Michele Montandon
Private Citizen

Ms. Montandon, a family physician and former CDC global health leader, expressed deep
concern about the growing spread of vaccine misinformation and its effects on public trust and
health systems. Drawing from her international  experience treating vaccine -preventable
diseases, she condemned recent political interference in public health leadership and decision-making, including the removal of ACIP members and changes to vaccine guidance outside
standard scientific channels. She cited the tragic consequences of misinformation, including a recent attack on CDC headquarters, and warned that confusion among physicians and families
is already escalating. Ms. Montandon urged the restoration of science -based leadership at HHS
and CDC, emphasizing that delays or di sruptions to vaccination endanger public safety and
erode confidence in the healthcare system.

Dr. Judy Stone, MD
Private Citizen

Dr. Stone, an infectious disease physician with over 40 years of experience, provided a powerful
account of witnessing children die from vaccine- preventable diseases. She reminded the
committee of the tremendous progress vaccines have achieved in reducing child mortality and
disease incidence in the U.S. Dr. Stone warned that misinformation and vaccine hesitancy are
reversing these gains, citing the resurgence of measles and other infections. She emphasized
that measles is highly contagious and can cause s evere complications, including hospitalization
and death. Dr. Stone urged ACIP to protect access to vaccines, maintain school vaccination
requirements, and uphold its duty to safeguard community health, stressing that society must
not go back to the pre -vaccine era.
 Mr. Scott Bertani
HealthHIV

Mr. Bertani, director of advocacy at HealthHIV, urged the committee to uphold ACIP’s legacy as
an independent, science -driven body. He highlighted the public health importance of the
hepatitis B birth dose and combination vaccines such as MMRV, which protect infants and
reduce the long- term disease burden. He noted that declining vaccine uptake threatens
individuals with chronic illnesses and immunocompromised populations, including people living
with HIV. Mr. Bertani outlined three recommendations: preser ve the evidence- based ACIP
process, maintain the full immunization schedule as published, and reinstate universal COVID -
50
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  19 vaccination for all individuals aged six months and older. He concluded by stressing that
weakening these frameworks risks confusion, stigma, and inequities in access to care.
 Evan Sachs
Washington Heights– Inwood Mask Bloc

Mr. Sachs, founder of the Washington Heights –Inwood Mask Bloc, spoke as a mutual aid
provider and journalist. He compared vaccination to traffic laws and seatbelt use, describing them as shared rules that protect both individuals and communities. He argued that public
health requires collective responsibility, not personal preference, and that vaccines, while not perfect, are overwhelmingly effective and essential for community safety. Mr. Sachs also emphasized the importance of layered protections, including masking, given that no single
intervention is 100 percent effective. He encouraged continued public health measures
grounded in science and social responsibility.
 Ms. Melissa Kadri
Private Citizen
 Ms. Kadri, a Master of Public Health student, offered an emotional testimony describing the loss
of her uncle to COVID -19 and the subsequent death of her aunt from grief. She spoke about the
devastating impact on her family and the broader implications of restricted vaccine access. Ms.
Kadri emphasized the importance of maintaining herd immunity and cautioned that delaying or
limiting childhood vaccinations contradicts scientific evidence and endangers  lives. Using her
family’s story as an example, she implored the committee not to alter vaccine schedules in ways
that could lead to preventable deaths and suffering, urging members to remember the human
cost of their decisions.
 Due to time constraints, Dr. Kulldorff announced that the discussions and votes on the MMRV
and Hepatitis B vaccines  would continue on September 19, 2025. Summaries of those
discussions and votes are included in the sections above. The meeting was then recessed until September 19, 2025, at 8:30 a.m. EST.

FRIDAY : SEPTEMBER 19, 202 5

WELCOME AND ROLL CALL

Call to Order/Roll Call

Dr. Martin Kulldorff, Chair of the ACIP, convened the meeting on September  19, 2025. Dr. Mina
Zadeh, ACIP Executive Secretary from the CDC, welcomed the committee, followed by a roll call of members, ex officio members, and liaison representatives, each of whom announced
their presence .

AGENCY UPDATES
 The Centers for Disease Control and Prevention (CDC)
 Dr. Brandi Limbago, representing CDC’s National Center for Immunization and Respiratory
Diseases (NCIRD), provided updates on response and preparedness activities. As of
51
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  September 16, 2025, CDC confirmed 1,491 measles cases across 42 jurisdictions, the highest
since 1992. Of these, 86 cases were linked to 38 outbreaks, compared with 69% of cases and
16 outbreaks in 2024. Most measles introductions originated from U.S. trav elers returning from
countries with active measles transmission, leading to outbreaks in under -vaccinated
communities. Despite these increases, the overall risk to the general population remains low
due to high vaccine coverage and population immunity.

She also reported on preparations for the 2025– 2026 respiratory virus season, focusing on
influenza, COVID -19, and RSV. Current data show low flu and RSV activity but increasing
COVID -19 activity nationwide, with elevated emergency department visits and hospitalizations,
particularly among children under 5, youth 5– 17, and adults 65 and older. CDC is taking a
coordinated approach to address these viruses by aligning programs, data systems, outreach, and communications. Additionally, the agency continues to monitor other respiratory pathogens,
including Mycoplasma, Group A Streptococcus, and Pertussis.

Dr. Chris Braden provided an update on a significant outbreak response led by the National
Center for Emerging and Zoonotic Infectious Diseases. On September 1, CDC received reports
from local sources of suspected viral hemorrhagic fever in the Kasai Provi nce of the Democratic
Republic of Congo, which was later confirmed as Ebola virus Zaire. The index case was a
pregnant woman admitted to Bulap General Hospital on August 20 with high fever, bloody
diarrhea, hemorrhaging, vomiting, and weakness; she died on  August 25 from multi -organ
failure. Two healthcare providers who treated her also became ill and died.
 Genomic sequencing at the DRC’s National Public Health Laboratory indicated that the virus is
genetically distinct from viruses in previous Ebola outbreaks, suggesting a new spillover event
from wildlife. The DRC government promptly confirmed the outbreak and collaborated with CDC to initiate an emergency response. CDC has maintained a partnership with DRC for over 20
years, operating a country office since 2002 with about 30 staff members supporting laboratory
capacity, workforce training, and public healt h infrastructure.
 As of September 15, there were 37 confirmed cases and 19 deaths, with additional suspected
cases under investigation. Approximately 944 contacts have been identified, and vaccination of
healthcare workers and contacts began on September 13, with 369 vaccin ations completed by
September 15. All confirmed cases remain confined to Kasai Province, specifically the Bulabia
health zone. The actual extent of the outbreak may be greater than currently known, though no
related cases have been reported outside the DRC  or in the United States, and the overall risk
to the U.S. public remains low.

CDC issued a Health Alert Network advisory for U.S. public health departments and clinicians
outlining case identification, testing, and biosafety recommendations. CDC headquarters is
coordinating with its DRC country office, which has deployed additional staff to Kasai Province
and Kinshasa to assist with response efforts. Technical support focuses on laboratory testing,
surveillance, case investigation, contact tracing, and infection prevention and control measures.

Food and Drug Administration (FDA)

Dr. Tracy Beth Hoeg from the Food and Drug Administration (FDA) provided updates on recent
regulatory actions and announcements. The four currently approved COVID -19 vaccines,
MNEX Spike, Spikevax, Coity, and Newacovid, are indicated for adults aged 65 yea rs and older,
as well as for individuals at increased risk for severe COVID -19. Newacovid is authorized for
individuals aged 12 years and older, while Spikevax is authorized for those aged six months and
52
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  older. The previous Emergency Use Authorizations (EUAs) for Novavax, Pfizer, and Moderna
have been revoked.
 For the approved vaccine formulations, there are three ongoing post-marketing commitments,
including studies on the persistence of the spike protein and associated symptoms, and randomized, saline placebo- controlled trials to evaluate safety and efficacy. Dr. Hoeg
emphasized the importance of these trials, noting that real -world evidence can sometimes be
misleading, citing a recent example involving the hepatitis B vaccine and apparent protection against bronchopulmonary dysplasia, which was likely due to healthy vaccine bias.
She also announced that randomized controlled trials will now be required to assess the safety of administering multiple vaccines concurrently. In addition, the live attenuated ICK vaccine for
chikungunya virus has been temporarily suspended due to safety concerns.
 Centers for Medicare and Medicaid Services (CMS), Health Resources and Services
Administration (HRSA), Indian Health Service (IHS), and National Institutes of Health (NIH) did
not report updates.

COVID -19 VACCINES

Dr. Retsef Levi (ACIP Work Group Chair) introduced the COVID- 19 Work Group’s immediate
goals, which focused on discussing recently authorized vaccine products and determining which populations and subgroups should receive recommendations. Members discussed three
possible options, which were to recommend, not recommend, or make an individual -based
decision, and planned to define each later in the day. The work group emphasized the need to clearly communicate all risks and uncertainties to patients, noting that the current Vaccine
Information Statement (VIS) does not accurately reflect the full scope of these concerns and
should be updated for greater clarity and consistency. Members agreed that ACIP and its work
groups should be able to consider any relevant data or information that supports vaccine policy decisions. Three focus clusters were established based on members’ expertise to summarize
available evidence, identify key issues and knowledge gaps, and develop potential policy
options for review by ACIP. The work group reaffirmed its commitment to using all relevant
published and unpublished data, including real -world experience, and to focusing on
personalized risk -benefit analysis rather than general statements about safety or effectiveness.
Members agre ed to maintain respectful debate and transparency to ensure all perspectives and
opinions are represented.
 Dr. Arjun Srinivasan (CDC/NCIRD) shared updates on COVID- 19 epidemiology. He explained
that the data presented and discussed in this section come from the COVID -19–Associated
Hospitalization Surveillance Network (COVID -NET). COVID -NET is one of three RESP -NET
platforms, along with RSV -NET and FluSurv -NET, that collect data using similar methods and
catchment areas on laboratory -confirmed COVID -19, RSV, and influenza -associated
hospitalizations. It is a collaborative effort between CDC and state and local health departments
that share data through cooperative agreements.
 COVID -NET is a collaborative, population- based surveillance system that collects data from
more than 300 acute care hospitals in 185 counties across 13 states, representing about 10% of
the U.S. population. It gathers two primary types of information: population -based hospitalization
rates and detailed clinical data from a stratified sample of patients. These data include demographics, outcomes, underlying conditions, treatments, and discharge diagnoses.

53
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  The system’s primary purpose is to monitor laboratory -confirmed COVID -19–associated
hospitalizations among children and adults and provide timely information to decision- makers
and the public. Hospitalization rates are updated weekly to assess disease burden and trends,
while clinical data help identify who is most at risk and evaluate illness severity. A COVID -NET
case is counted when a resident of the catchment area tests positive for SARS -CoV-2 within 14
days before or during hospitalization. Similar def initions are used for RSV and influenza
surveillance systems.
 Dr. Srinivasan noted that there has been ongoing interest in distinguishing between
hospitalizations due to COVID -19 and those for COVID -19 illness. During the early stages of the
pandemic, when there was no immunity or vaccination and asymptomatic transmi ssion was
common, hospitals screened all patients upon admission. This practice often identified patients
who tested positive for SARS -CoV-2 but were hospitalized for unrelated reasons, such as
surgery or childbirth. To address this, COVID -NET implemented an algorithm to identify
hospitalizations primarily due to COVID -19, based on chief complaint and history of present
illness. Data using this approach, dating back to March 2020, are posted monthly on the public
COVID -NET dashboard. Although routine univer sal screening of all hospital admissions has
largely ended, COVID -NET continues to use this algorithm to maintain consistency in
surveillance.

Several factors must be considered when defining hospitalizations due to COVID -19. A positive
SARS- CoV-2 test can influence the decision to admit a patient with comorbidities or other
underlying conditions. At the same time, the presence of comorbidities o r other conditions can
also affect the decision to accept a SARS -CoV-2–positive patient. Data obtained from medical
records, such as test results, treatments, discharge diagnoses, and coding, may lead to
misclassification of hospitalizations as COVID -19-related or unrelated. ICD -10-CM codes in the
U.S. are designed for billing and administrative purposes, not surveillance, and may either overcount or undercount true cases. In some instances, a COVID -19 ICD code can be used
only to indicate a positive test r ather than hospitalization for COVID -19 illness.
 COVID -NET uses a standardized process to determine whether hospitalizations are due to
COVID -19. This process relies on information from the chief complaint and history of present
illness recorded at admission. Hospitalizations are classified as non- COVID -19-related if the
admission was for obstetric care, surgery, psychiatric reasons, trauma, or for newborns
hospitalized at birth. For remaining cases, if the medical record documents fever, respiratory
symptoms, a COVID -19–like illness, or suspicion for COV ID-19, the hospitalization is classified
as due to COVID -19. Cases that do not clearly fit these criteria are reviewed by two COVID -
NET physicians, with a third review if needed. Suppose a patient’s medical record indicates that
a positive SARS -CoV-2 test was incidental or that the hospitalization occurred for an unrelated
reason, such as a localized infection or a surgical procedure. In that case, the case is classified
as not related to COVID -19.
 Using this algorithm, 87% of hospitalizations among SARS -CoV-2–positive patients in COVID -
NET were determined to be due to COVID -19. Rates have increased over time, likely because
universal screening of asymptomatic patients is no longer standard. Among children, 89% of hospitalizations were due to COVID -19, and the percentage increased with age in adults. Adults
aged 65 years and older accounted for 70% of COVID -19–associated hospitalizations, with 91%
of those admissions determined to be primarily due to COVID -19.

COVID -NET balances the need for detailed clinical data with the workload of chart abstraction.
Data collection can be limited by timing and access, since ICD -10 codes are assigned after
54
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  discharge and may only be available in billing systems. To address this, surveillance officers
also review discharge summaries to capture conditions that developed during hospitalization.
Combining discharge summaries with ICD -10 codes provides a more complete picture of each
case and reduces bias that can occur when relying solely on billing data for public health
surveillance.

COVID -NET examined classif ying hospitalizations as being due to COVID -19using two different
approaches: ICD -10-CM discharge diagnoses and the network’s reason- for-admission
algorithm. Data from the 2023– 2024 season were used since ICD -10-CM codes are not yet
available for the 2024– 2025 season. During this period, COVID -NET identified more than
66,000 hospitalizations among patients of all ages, of which 7,279 were sampled for medical record abstraction. Using ICD -10-CM codes and discharge diagnoses, 81% of sampled
hospitalizations had a COVID -19 discharge code listed in one of the first nine coding positions,
52% had a sepsis or respiratory -related diagnosis, and 88% had either a COVID -19 ICD -10
code or a respiratory diagnosis. 12% of cases had neither  a COVID -19 ICD -10-CM code nor
sepsis or respiratory -related discharge diagnosis .
 Applying the reason- for-admission algorithm to the same sample, 85% of hospitalizations were
classified as due to COVID -19. Of these, 91% also had either a COVID -19 ICD -10 code or a
sepsis or respiratory -related diagnosis. Among the remaining 15% classified as hospitalizations
with COVID -19, 64% had a COVID -19 ICD -10 diagnosis code.

Dr. Srinivasan summarized that the two classification methods show strong agreement. Overall, 88% of hospitalizations had a COVID -19 ICD -10 code or a respiratory -related diagnosis, and
85% were identified as COVID -19 as the likely primary reason for admiss ion. 92% of
hospitalizations identified through the reason- for-admission approach also had a COVID -19
ICD-10 code or a sepsis or respiratory diagnosis. The reason -for-admission approach is more
conservative than relying solely on discharge diagnoses and can be completed more quickly.
These findings support the notion that COVID -NET’s methods provide a balanced approach to
timeliness, accuracy, and population representation.

COVID -19–associated hospitalization rates per 100,000 population were determined by age
group and reflect the cumulative risk of hospitalization for the 12 months from October 2024
through September 2025. The rates were based on the surveillance standard, which includes
hospitalized residents in the COVID -NET catchment area who tested positive for SARS -CoV-2.
Hospitalization rates were highest among adults aged 65 to 74 years and 75 years and older, as well as among infants younger than 6 months. Because no vaccine products are approved for
infants under 6 months of age, protection against hospitalization must come from maternal
vaccination.

A significant proportion of adults hospitalized due to COVID -19 experienced severe in- hospital
outcomes, including admission to the intensive care unit and in- hospital death. About 15% of
adults hospitalized with COVID -19 were admitted to the ICU, and in -hospital death occurred
more frequently among adults aged 50 years and older. Among all adults hospitalized due to
COVID -19 who died in the hospital, 84% were aged 50 years and older. These data include only
deaths that occurred during hospitalization, although additional COVID -19–associated deaths
occur outside the hospital, including some within 30 days after discharge.

Different respiratory viruses affect age groups differently, with the greatest overall impact seen
at the extremes of age. Cumulative data show that RSV causes the highest burden of
respiratory disease in children under one year. COVID -19 has the greatest impact on older
55
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  adults but also remains a significant cause of hospitalization among infants, with rates
comparable to influenza during October 2024 -2025, a high- severity influenza season  that was
the most severe since the 2010– 2011 season. COVID -19–associated hospitalization rates
among infants younger than 6 months have remained close to those among adults aged 65 to
74 years, but in recent weeks have risen more rapidly, reaching 223 per 100,000 c ompared to
194 per 100,000 among adults, a 14% higher rate among infants  compared to adults aged 65 to
74.

Dr. Srinivasan shared an update to a peer -reviewed study published in 2021, which had
informed a previous infographic summarizing the relative risk of hospitalization among individuals with chronic conditions compared to those without. Data sources for the updated
analysis included three primary datasets: COVID -NET data on hospitalizations due to COVID -
19 from October 2022 through September 2023; the Behavioral Risk Factor Surveillance System (BRFSS), the largest ongoing health survey system in the world th at collected data
annually from hundreds of thousands of community -dwelling U.S. adults; and population data
from the U.S. Census provided by the National Center for Health Statistics.

The analysis methodology was complex. COVID -NET provided weighted counts of individuals
hospitalized due to COVID -19 who had underlying conditions, limited to community -dwelling
adults aged 18 years and older, for consistency with BRFSS data. Weighted coun ts of adults
with and without chronic diseases of interest were calculated using BRFSS data and state
population modeling. Adjusted rate ratios of hospitalization rates for adults with versus without
chronic conditions were then calculated. Chronic conditi ons examined were limited to those
included in the BRFSS survey  and included coronary artery disease, history of stroke, diabetes
mellitus, chronic kidney disease, COPD, asthma, obesity, severe obesity, and current smoker .

Findings showed that the prevalence of most chronic conditions among adults hospitalized due
to COVID -19 was higher than in the general population. Among adults, most chronic conditions
increased the risk of being hospitalized due to COVID -19. The risk for hospitalization conferred
by several conditions, such as coronary artery disease, diabetes, and obesity, appeared to
decline with age but this may have reflected challenges in adjusting for coexisting conditions or
low prevalence of some diseases within s pecific age groups; for example, severe obesity was
uncommon among adults aged 75 years and older, while COPD was uncommon among adults
younger than 50 years.
 The analysis also showed that the risk for hospitalization due to COVID -19 increased with both
the number of chronic conditions and with age. Having multiple comorbid conditions and older age were the strongest risk factors for hospitalization due to COVID -19 identified among adults .
Adults with three or more underlying conditions were nearly six times more likely to be
hospitalized due to COVID -19 compared with those with no underlying conditions.
Hospitalization rates were 18.5 times higher among adults aged 75 years and older compared with those aged 18 to 49 years, making age 75 and above the greatest identified risk factor for
hospitalization.

The analysis had several strengths, including the use of data from a robust COVID -19
hospitalization surveillance system that enabled comparisons across state -level prevalence data
and allowed examination of how specific conditions, multiple comorbidities,  and age contributed
to hospitalization risk. However, there were also limitations. The results remained preliminary
and under review. The analysis was limited to community -dwelling adults and did not include
children or individuals living in long- term car e facilities, where risks may have differed. Some
conditions tended to co -occur, such as diabetes and chronic kidney disease, and adjustments
56
Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  for these comorbidities could not always be made due to limited data, particularly in younger
adults. In addition, differences in rate ratios by outcomes (e.g., ICU admission) or by race and
ethnicity could not be assessed due to the sparse data.

Dr. Malone asked whether there was a significant overlap and diagnostic difficulty between
COVID -19 and other influenza- like illnesses.

Dr. Srinivasan confirmed that the symptoms of COVID -19 overlapped almost entirely with those
of other respiratory illnesses.

Dr. Malone noted that when he had previously asked a CDC representative about the specificity
and sensitivity of the diagnostic tests used, he was told those measures were “academic.” He
expressed concern that sensitivity and specificity are fundamental to  data validity and stated
that diagnostic testing for COVID -19 has had limitations in both areas, which were not reflected
in the models.

The NCIRD SME explained that the tests used in COVID -NET were FDA -approved diagnostic
tests performed in hospitals and medical clinics nationwide. The SME clarified that COVID -NET
did not conduct testing directly and that all tests were performed at the tr eating provider's
discretion.

Dr. Malone stated that this confirmed the tests had known limitations in sensitivity and specificity
that could affect data interpretation.

The NCIRD SME acknowledged that all clinical tests have defined sensitivity and specificity
values but emphasized that the tests used were FDA -approved and used to identify patients
who tested positive for SARS -CoV-2.

Dr. Malone added that if the tests were only 80% specific, the underlying classification of
COVID -19 cases would be similarly ambiguous.

Dr. Natalie Thornburg, NCIRD laboratory SME, clarified that all tests used in COVID -NET had
re
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Summary: MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)     SEPTEMBER  18-19, 2025   MEETING SUMMARY                                                                            Trade names are used for identification purposes only and do not indicate endorsement.           2  Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  THURSDAY : SEPTEMBER 18, 202 5    WELCOME AND ROLL CALL     Call to Order/Roll Call     Dr. Mina Zadeh, ACIP…