summary 2025 04 15 16 508

MEETING OF THE ADVISORY
COMMITTEE ON IMMUNIZATION
PRACTICES (ACIP)
APRIL 15-16, 202 5
MEETING SUMMARY
Trade names are used for identification purposes only and do not indicate endorseme nt.
2 TUESDAY : APRIL 15, 2025
WELCOME AND INTRODUCTIONS
Call to Order/Roll Call
Dr. Keipp Talbot (ACIP Chair) called the April 15, 2025, Advisory Committee on Immunization
Practices (ACIP) meeting to order.  Dr. Melinda Wharton (ACIP Executive Secretary) made
opening announcements about the availability of presentation slides on the ACIP website, the
scheduled oral public session, and the written public comment process  through regulations.gov
at Docket ID CDC -2025 -0017 . She reviewed conflict of interest (COI) policies for ACIP
members. She welcomed and introduced the new committee members: Ms. Karyn Lyons and
Dr. Jane Zucker. Dr. Keipp Talbot conducted a roll call  to establish  a quorum. A list of members,
ex offici o members , and liaison representatives is included in the appendices at the end of this
summary document. No COIs were identified for the first day of this meeting. Dr. Chen
disclosed prior involvement with VLA2001 vaccine trials, noting service on data and safety
monitoring boards for Valneva vaccine trials that concluded in August 2024. She also co -
authored a paper with Valneva scientists, published in September 2024, on chikungunya
vaccine development, and received no compensation from industry fo r that work. To avoid the
perception of a conflict of interest related to these past activities, she will abstain from voting on
the chikungunya vaccine recommendations.
MPOX VACCINE
Dr. Faisal Minhaj (CDC/NCEZID) provided an overview of the monkeypox virus (MPXV).  It is
within the Orthopoxvirus genus and the Poxviridae family,  in the same genus that contains
variola virus, the causative agent of  smallpox. It was discovered in 1958 following two outbreaks
of a pox -like disease in a research monkey colony. Although the animal reservoir is unknown, it
is likely to be small African mammals.  The World Health Organization (WHO)  implemented the
preferred term “mpox” for the disease in  Novembe r 2022. There are two clades of MPXV. Clade
I is historically associated with greater disease severity in a higher proportion of people in
central Africa. Clade II, which is found in West Africa, was the cause of the 2022 global
outbreak.
The first human case of mpox was identified in the Democratic Republic of the Congo (DRC)  in
1970. In 2003, a U .S. outbreak of 47 cases occurred when small mammals from Ghana infected
pet prairie dogs. In 2017, an outbreak of 122 cases occurred in Nigeria, involving 17 states . This
outbreak followed a period of very few reported cases for decades in Nigeria and West Africa.
Multiple travel -associated cases followed, including 2 U .S. cases in 2021. The ongoing global
Clade II mpox  outbreak followed in 2022.
The first case of the global mpox outbreak was identified in May 2022 in the United Kingdom .
This outbreak  primarily affected gay, bisexual, and other men who have sex with men (MSM). I t
spreads  through  close skin -to-skin contact, including sex. Deaths have primarily occurred
among individuals with severe immunocompromise due to advanced HIV.  The U .S. case counts
and deaths comprise  1/3 of cases and deaths globally, with more than 30,000 cases and more
than 60 deaths in the U.S.
3
 During the current outbreak, the peak in U .S. cases occurred in summer 2022 ; since that time,
cases have continued to occur in the U.S . As of March 2025, cases continue to occur, with a 7 -
day moving average in recent months ranging from  3.3 to 1.2 cases per day .

Due to the ongoing outbreak, in February 2023 , the ACIP recommended  the 2 -dose JYNNEOS®
vaccine series for persons aged 18 years and older at risk of mpox during an mpox outbreak.
Dose 2 is administered one month after Dose 1 .  Public health authorities determine whether
there is an mpox outbreak; a single case may be considered an mpox outbreak at the discretion
of public health authorities. Other circumstances in which a public health response may be
indicated include the ongoing risk of mpox introductio n into a community due to disease activity
in another geographic area.

In October 2023 ACIP made an interim recommendation for use of JYNNEOS vaccine in the
current outbreak, recommending vaccination with the 2 -dose JYNNEOS vaccine series for
persons aged 18 years and older at risk for mpox .  Dose 2 should be administered 28 days after
Dose 1, and persons at risk include the following:
Gay, bisexual, and other men who have sex with men (MSM), or a person who has sex with
MSM who in the past 6 months have had one of the following:
• A new diagnosis of ≥ 1 sexually transmitted disease
• More than one sex partner
• Sex at a commercial sex venue
• Sex in association with a large public event in a geographic area where mpox
transmission is occurring
Sexual partners of persons with the risks described in above
Persons who anticipate experiencing any of the above
This is an interim recommendation which should be revisited in 2 -3 years.
Even a s the  global Clade II outbreak continues, there  has also been an increasing number of
cases in the DRC  and surrounding central and east African countries , resulting in travel -
associated Clade I cases in multiple countries.
From June 2022 through September 2024, in the U.S. overall , JYNNEOS vaccine coverage
among eligible individuals was 42.2% for 1  dose and 26.2% for the 2-dose  series .  Modeling
data suggests that any increase in coverage reduces the risk of outbreaks and that low
coverage (<50%) could promote larger outbreaks.
The case trend for mpox cases among children and adolescents is similar to that for adults, with
the peak of cases occ urring  in the summer and fall of 2022 , and cases sporadically  occurring
since then.
Previously , there w ere no data evaluating JYNNEOS  in children <18 years . An NIH -sponsored
trial completed last year evaluated JYNNEOS  in 12 –17-year-old adolescents.   With these  new
data, the work group is proposing to extend the current recommendations down to 12 -17 year -
old adolescents.
Proposed recommendation 1:
ACIP recommends the 2 -dose* JYNNEOS vaccine series for persons 12 –17 years of age at risk
of mpox during an mpox outbreak§.
*Dose 2 administered one month after Dose 1
4
  §Public health authorities determine whether there is an mpox outbreak; a single case may be
considered an mpox outbreak at the discretion of public health authorities. Other circumstances
in which a public health response may be indicated include ongoing risk of introduction of mpox
into a community due to disease activity in another geographic area.
Proposed recommendation 2:
ACIP recommends vaccination* with the 2 -dose† JYNNEOS vaccine series for persons aged
12–17 years at risk for mpox §
* Interim recommendation to be revisited in 2 -3 years
† Dose 2 administered 28 days after Dose 1
§ Persons at risk :
1. Gay, bisexual, and other men who have sex with men (MSM), or a person who has sex with
MSM who in the past 6 months have had one of the following:
• A new diagnosis of ≥ 1 sexually transmitted disease
• More than one sex partner
• Sex at a commercial sex venue
• Sex in association with a large public event in a geographic area where mpox
transmission is occurring
2.  Sexual partners of persons with the risks described in above
3.  Persons who anticipate experiencing any of the above
The Evidence to Recommendation ( EtR) frameworks  on these two proposed recommendations
will be presented at this meeting, with the expectation of voting at the June 2025 ACIP meeting.
Dr. Buddy Creech (Vanderbilt) presented findings on the safety and immunogenicity of mpox
vaccination in adolescents. He described the study as a Phase 2, randomized, open -label,
multisite trial (DoSES) designed to inform public health strategies for using the Modified
Vaccinia Ankara (MVA)  [Bavarian Nordic  (BN), JYNNEOS ] vaccine against mpox. Stage 1
evaluated the FDA -approved 2 -dose subcutaneous (SC) regimen compared to two separate
intradermal dose -sparing regimens in adults aged 18 –50 years. Stage 2 ass essed the
noninferiority of the 2 -dose SC regimen in adolescents aged 12 –17 years compared to adults
aged 18 –50 years.
MVA -BN was administered subcutaneously on Days 1 and 29 to healthy, vaccinia -naïve
adolescents aged 12 –17 years, compared to adults aged 18 –50. The study aimed to support
licensure of JYNNEOS for use in adolescents. Enrollment targeted a cohort representative of
the U .S. population based on 2020 Census data, intending to include  at least 25% of
participants aged 12 –14 years.

The study population included 315 adolescents aged 12 –17 years , of whom 161 were 12 -14
years of age and 211 were adults. All participants received Dose 1, and nearly all received Dose
2. Almost all  participants completed their primary endpoint evaluation at  Day 43. Solicited
systemic and local reactions were similar between adolescents and adults. Erythema,
induration, and pruritus were more comm on in both groups after Dose 2. The most common
systemic reactions were fatigue, headache, and myalgia, occurring at similar frequencies after
both doses.

5
 The severity of solicited adverse events within 7 days of Dose 1 was 55% mild, 36% moderate,
and 2% severe among adolescents, and 50% mild, 31% moderate, and 3% severe among
adults. Following Dose 2, adolescents reported 36% mild, 42% moderate, and 6% seve re
events, while adults reported 35% mild, 37% moderate, and 19% severe events. Erythema and
induration were the most common severe reactions.

The most frequent local reactions were pain at the injection site, erythema, and injection site
nodules. Injection site nodules were reported by 117 adolescents (37%), typically appearing at
the beginning of the second week, and by 7 8 adults (59%). Nodule rates were similar between
younger and older adolescents (40% vs. 34%). Discoloration was reported by 53 adolescents
(17%) and 38 adults (28%).
Dizziness was reported more frequently in adolescents than in adults. No event resulted in
syncope  or medical attention; 7 of 8 occurred within 1 day of vaccination . Rates were similar to
those reported with other adolescent vaccines . Three adolescents and 4 adults received only
the first dose of the vaccine.  Two adolescent participants became pregnant during the study.
Children were born without complications or congenital anomalies.
Immunogenicity was assessed using a vaccinia virus (Western Reserve strain) plaque -reduction
neutralization titer (PRNT ) assay.  Peak humoral responses ( Day 43) after a 2-dose regimen in
adolescents were noninferior to those in adults.   Geometric mean titers at Day 43 were higher in
adolescents than in adults, and seroconversion  at Day 43  (defined as the proportion of
participants with at least a 2 -fold rise in antibody titer compared to pre -Dose 1)  was very hig h
and similar in the two groups .
MPXV -specific PRNT assays are still underway . Neutralization in the presence of complement
appears more representative of in vivo neutralization ; testing of various complement sources
has led to the identification of critical reagents needed for neutralization across both Clade I and
Clade II MPXV .  One hundred paired samples are being tested against Clade I and Clade II
MPXV in the presence of complement .
Limitations included the study population being different compared to the global pediatric
population at risk of mpox .  Efforts were made to ensure that the population was representative
of the U.S. population and that the ages of v olunteers were distributed across the adolescent
age group.
Dr. Creech concluded that the interim data from this Phase 2 clinical trial demonstrate that the
MVA -BN vaccine is safe and well -tolerated in adolescents aged 12 –17 years.  The peak
geometric mean titer ( GMT ) met prespecified noninferiority criteria for adolescents aged 12 –17
years compared to adults aged 18 –50 years.  These findings are relevant to U.S. adolescents
and areas where mpox is endemic, such as the DRC. Evaluations in younger children are
needed to protect  those most vulnerable, particularly given  ongoing transmission among
children in the DRC and neighboring African countries .
Dr. Shaw inquired whether there was a difference in complement -mediated enhancement
between adolescents and adults , and if so, whether it was due to the early or late  components
of complement.
Dr. Creech responded that, in general, there is no difference between adolescent and adult
neutralization. However, differences are observed with MPXV and other viruses when
conducting plaque reduction neutralization assays. For MPXV, complement is require d to
neutralize both mature virions and extracellular  enveloped virions.
6
 Dr. Beigel added that  the answer remains a work in progress. Assays using complement have
been conducted, and increasing titers were observed. However, investigation into the underlying
mechanisms has not yet begun. That work remains ongoing.
Dr. Schec hter asked how soon after the immunization did dizziness occur, compared to
dizziness and syncope with other adolescent vaccines.
Dr. Creech shared that all events occurred within one day of vaccination, with minimal variation.
The characteristics were consistent with those typically seen in adolescents receiving Tdap,
HPV, or influenza vaccines. These included transient, mild, and s elf-limited reports of
lightheadedness that resolved quickly , reflect ing patterns commonly observed in vaccinated
adolescents.
Dr. Schec hter raised the question regarding reports of more severe erythema and whether
these correlated with discoloration or nodule formation, specifically, whether multiple
manifestations of local reactions tended to occur together.
Dr. Creech shared that s evere erythema was defined as greater than 10 cm, and severe
induration or swelling, distinct from nodule formation, was defined as greater than 10 cm. While
some correlation existed between erythema and nodule formation, the association was
inconsistent ; not all individuals with erythema developed nodules, and not all individuals with
nodules had a history of preceding erythema. Generally, local reactions appeared around one
week post -vaccination. Nodules in adolescents tend to be s maller than those in adults. The
largest in adults measured up to 7 or 8 cm, while the largest in adolescents was 6 cm. Most
adolescent nodules  were under 2 cm, approximately a finger's width . These reactions typically
resolved over time, were not usually painful or distressing, and in some cases, severe erythema
was accompanied by pruritus at the injection site. While local reactions often clustered, they did
not consistently present together . However, erythema was frequently accompanied by pruritus
and oc casionally by nodule formation.
Dr. Faisal Minhaj (CDC/NCEZID) presented the EtR  for vaccination with JYNNEOS for
adolescents at risk of mpox during outbreaks , focused on the question of ACIP recommending
the 2 -dose JYNNEOS vaccine series for persons 12 –17 years of age at risk of mpox during an
mpox outbreak .
Regarding the public health problem, Dr. Minhaj stated that two distinct outbreaks are occurring:
Clade I and global Clade II. The DRC is the most affected by Clade I , and other countries have
identified travel -associated cases . The U.S. ranks among the countries with the highest burden
of disease due to Clade II. No week has passed without ≥1 reported case in the U.S. from May
2022 to March 2025. Cases have been identified in both adolescent and adult populations.
Clinical manifestations of mpox can be sev ere, especially in severely immunocompromised
persons  in whom the infection can result in death . The work  group determined that outbreaks of
mpox are of public health importance.
For benefits and harms, Dr. Minhaj restated earlier findings on the immunogenicity and safety of
JYNNEOS, confirming that the vaccine is safe and well tolerated in adolescents. The adolescent
arm of the study met the pre -specified criteria for noninferiori ty. Unsolicited related adverse
effects were primarily injection site reactions. Dizziness, commonly observed in this age group ,
is unlikely to represent a safety concern after vaccine administration . CDC vaccine safety data
sources for JYNNEOS include the  Vaccine Adverse Event Reporting System (VAERS), Vaccine
Safety Datalink (VSD), V -safe, and single -patient Emergency Investigational New Drug (EIND)
procedures. From 2022 to 2023, at least 1,245 persons <18 years of age received one or more
doses of JYNNEOS.  No serious adverse events were identified from any of these data sources.
The work group  determined that the desirable anticipated effects were large, the undesirable
7
 anticipated effects were small, and that the desirable effects outweighed the undesirable ones ,
favoring intervention.
Dr. Minhaj noted that the NIH rapidly completed trial recruitment for the values domain, with
participants expressing support for joining the trial to help friends. During outbreaks, pediatric
close contacts were vaccinated. The Adolescent Medicine Trials Network for HIV/AIDS
Interventions (ATN) surveyed youth advisors, with 12 out of 13 respondents expressing support
for vaccination. It remains uncertain what type of outbreak may occur in the future or how
adolescents would perceive their risk and the acce ptability of vaccination. The work group
concluded that the target population would "probably" perceive the desirable effects as large
relative to the undesirable effects. The work group  was torn on whether there was “possibly
important uncertainty or variability” and “probably no important uncertainty or variability” in how
much people value the primary outcome. The nature of the outbreak may impact how
adolescents view their risk and their likelihood of accepting  vaccination.
Dr. Minhaj described two surveys for the acceptability domain: one administered to Adolescent
Medicine Trials Network (ATN) providers and another to mothers of adolescents and younger
children. Of the 21 surveyed ATN providers who care for at-risk adolescents, over half already
offered the mpox vaccine. 95% reported they would recommend the vaccine for eligible patients
and expressed no concerns. The majority noted challenges the financial cost to the clinic being
the most frequently cited concern. The survey of mothers of children aged ≤18 years resulted in
indications that most mothers do not perceive their children as being at risk for mpox; however,
the intent to vaccinate was higher than expected.  The work group felt that the intervention
would “probably” be acceptable to key stakeholders.
For the health equity domain, Dr. Minhaj noted that Black adolescents represent a significant
proportion of mpox cases but a smaller proportion of vaccine uptake, reflecting known racial
inequities. No specific groups or settings would be disadvantaged by a recommendation for
JYNNEOS use during mpox outbreaks. Immunogenicity is consistent among immunocompetent
individuals aged 12 to 17 years. Vaccine implementation should ensure equitable access.
Endorsement by ACIP could support broad acceptance of the rec ommendation through
mechanisms such as insurance coverage, support from health departments, and availability in
pharmacies. The work group  concluded that the impact on health equity would probably
increase.
For the feasibility domain, Dr. Minhaj explained that a wide range of vaccinators are authorized
to administer the vaccine. Facility sites include public health departments, sexually transmitted
infection ( STI) clinics, adolescent health clinics, and pediatric offices. The vaccine uses the
same immunization information systems (IIS) and reporting infrastructure as other vaccines.
Limitations to access include poor availability in rural communities, high vaccine cost, and the
possibility that pediatricians m ay defer vaccination to STI or adolescent clinics. The 2 -dose
schedule, administered 28 days apart, requires follow -up and reminders. Once thawed and
refrigerated, JYNNEOS remains viable for either 4 or 8 weeks, allowing time to schedule the
second dose. Frozen storage is approximately 18 months. The work group  concluded that the
intervention is “probably” feasible to implement.
For the resource domain, Dr. Minhaj stated that JYNNEOS is commercially available and
supported by similar mechanisms for billing and reimbursement, including Medicaid, Medicare,
and 317 funding. Vaccines are generally considered a good use of resources du ring an
outbreak. However, the cost -effectiveness of vaccination during a future outbreak in
adolescents remains uncertain. The work group  concluded that the intervention would
“probably” be a reasonable and efficient allocation of resources.
8
 Overall, the work group  felt that t he desirable consequences clearly outweigh the undesirable
consequences in most settings , concluding the EtR presentation .
Ms. Moser asked whether the proposed recommendation is to change the starting age from 18
to 12, or whether the recommendations would be separate.
Dr. Minhaj responded that the recommendations would be separated, but the adolescent
recommendation would be aligned with the language in the adult recommendation.
Ms. Moser inquired whether mpox data collection has been impacted due to funding and staffing
changes.
Mr. Duffy shared that VAERS is still collecting reports.
Dr. Shaw requested comments on the ongoing Clade I outbreak in the DRC. Two distinct
outbreaks were noted: Clade IA, which is more rural and primarily affects children, with about
60–70% of cases linked to household transmission, and Clade IB, which is more urban and
occurs mainly among adults. Dr. Shaw asked whether this is still the case, whether there are
any known biological reasons for the differences in transmission, and which Cl ade I subtypes
have been observed in the U.S.
Dr. Minhaj commented that clade IA is predominantly seen endemically in the DRC and other
endemic countries. In the DRC , about 50% of the population is under 15 years of age ; given
this, it is not surprising that many cases occur among children. Population dynamics also differ,
with more crowded housing and other factors that do not directly translate to the U.S. There is
nothing specific about the virus that determines which po pulations are affected; rather, it
depends on the communities it enters. Clade I B is predominantly found in the eastern part of the
DRC and has spread to other countries. It has primarily affected heterosexual sex networks and
older populations, including adults. Again, the networks through which the virus enters, not a
biological difference  in the virus, influence transmission patterns. In terms of cases in the U.S., I.
Four cases of Clade I have been reported so far, all of which were travel -associated and
identified as Clade IB. Most travel -associated cases have been of Clade IB, al though a few
Clade IA cases have also been reported, including some  in other countries.
Dr. Schec hter inquired whether data on adolescent vaccination or vaccination in younger
children would likely become available in the coming months, based on its use in Africa, and
asked Dr. Creech whether any participants had been  evaluated for symptoms of myocarditis,
given the inclusion and exclusion criteria related to the condition. He inquired if myocarditis was
assessed during the trial or if it was noted as a pertinent negative or absence.
Dr. Minhaj noted that trials are underway to evaluate children younger than 12 years of age, and
once the data are available, they  will hopefully be presented.
Dr. Creech followed up and shared that there were no symptoms that would have triggered an
evaluation for myocarditis or pericarditis. This is consistent with existing data, which shows that
the vaccine does not appear to cause these conditions in teenager s. The eligibility criterion was
included out of an abundance of caution.
Mr. Duffy added that , based on CDC surveillance data, no cases of myocarditis have been
reported or identified in individuals under 18 years of age from any listed surveillance systems.
Dr. Fryhofer pointed out that the website and the presentation contained differing statements
regarding the balance of consequences.
Dr. Minhaj clarified that there are two EtR responses, and the next.
Dr. Kurilla asked how many children aged 12 to 17 would be considered high risk under the
recommendation. Concerns were raised about how healthcare providers with low caseloads of
9
 these individuals and pharmacies in areas with low population density  would manage
administration. Challenges may still exist in ensuring access for at -risk individuals .
Dr. Minhaj clarified that the proposed recommendation applies to the use of JYNNEOS during
an mpox outbreak. This is not limited to the 2022 outbreak; it could also apply to future
outbreaks, like the 2003 incident involving infected pet prairie dogs. The recommendation allows
public health authorities to advise the use of JYNNEOS for adolescents deemed  to be at risk.
This allows the CDC  or public health authorities  to issue guidance identifying at -risk populations
and recommending vaccination for adolescents, if appropriate. It was noted that the proposed
question appears to be related to the following item for discussion.
Dr. Minhaj then presented the evidence to support the recommendation framework for the
routine use of JYNNEOS vaccine for adolescents at risk of mpox during  the current outbreak
(proposed ACIP recommendation 2) . It was noted that globally , Clade I and Clade II outbreaks
are currently ongoing. In the United States,  most vaccine doses were administered during the
summer and fall of 2022. Overall vaccine coverage among the adult population at risk is
approximately 42% for 1 -dose and 26% for 2 -dose, which remai ns low and has not significantly
changed over the past year. This is important because once population immunity exceeds 50%
for at least 1 -dose, the likelihood of large outbreaks decreases significantly. Regardless of
reaching the 50% threshold, any increa se in vaccine coverage is correlated with a decrease  in
cases. The work group  determined that mpox outbreaks are of public health importance.
Dr. Minhaj highlighted new safety and immunogenicity data for the benefits and harms domain
for JYNNEOS in adolescents. The adolescent arm met the prespecified criteria for non-
inferiority and was well -tolerated  in this population. Vaccine administration data show that over
1,200 adolescents received the vaccine nationwide, with no serious adverse events reported
from any data sources. Based on these findings, the work group  determined that the desirable
anticipated effects are “large”, while the undesirabl e effects are “small”. The work group  favored
the intervention.
Dr. Minhaj noted that the NIH rapidly completed trial recruitment for the values domain, with
participants expressing support for joining the trial to help friends. During outbreaks, pediatric
close contacts were vaccinated. The Adolescent Medicine Trials Network for HIV/AIDS
Interventions (ATN) surveyed youth advisors, with 12 out of 13 respondents expressing support
for vaccination. The work group  felt that the target population “probably” felt that the desirable
effects are large relative to the undesira ble effects. The work group  was uncertain  on whether
there was “possibly important uncertainty or variability” and “probably no important uncertainty
or variability” in how much people value the main outcome, primarily due to the limited data on
this population.
For acceptability, Dr. Minhaj re -emphasized that most mothers do not perceive their children as
at risk for mpox; however, the intent to vaccinate was higher than expected. During the current
outbreak, v accines were primarily administered to adolescents through public health and STI
clinics. Of the 21 surveyed ATN providers who care for at -risk adolescents, over half already
offered the mpox vaccine. 95% reported they would recommend the vaccine for eligi ble patients
and expressed no concerns. The majority noted challenges with providing the vaccine, with
financial cost to the clinic being the most cited concern. The work group  felt that the intervention
would “probably” be acceptable to key stakeholders.
For the health equity domain, Dr. Minhaj reinforced that Black adolescents represent a
significant proportion of mpox cases but a smaller proportion of vaccine uptake, reflecting
known racial inequities. No specific groups or settings would be disadvantage d by a
recommendation for JYNNEOS use during mpox outbreaks. Immunogenicity is consistent
among immunocompetent individuals aged 12 to 17 years. Vaccine implementation should
10
 ensure equitable access. Endorsement by ACIP could support broad acceptance of the
recommendation through mechanisms such as insurance coverage, support from health
departments, and availability in pharmacies. The work group  felt the impact on health equity
would be “probably increase d.”
For the feasibility domain, Dr. Minhaj reminded the committee  that a wide range of vaccinators
are authorized to administer the vaccine for the feasibility domain. Facility sites include public
health departments, STI clinics, adolescent health clinics, and pediatric offices. The vaccine
uses the same IIS and reporting infrastructure as other vaccines. Limitations to access include
poor availability in rural communities, high vaccine cost, and the possibility that pediatricians
may defer vaccination to STI or adolescent clinics. The 2 -dose schedule, administered 28 days
apart, requires follow -up and reminders. Once thawed and refrigerated, JYNNEOS remains
viable for either 4 or 8 weeks, allowing time to schedule the second dose. Frozen storage is
approximately 18 months. The work group  felt that the intervention “probably” would be feasible
to implement.
For the resource domain, Dr. Minhaj reiterated that JYNNEOS is commercially available and
supported by similar mechanisms for billing and reimbursement, including Medicaid, Medicare,
317 funding,  and the Vaccines for Children ( VFC) program . Vaccines are generally considered a
good use of resources during an outbreak. However, the cost -effectiveness of vaccination
during a future outbreak in adolescents remains uncertain. The work group  concluded that the
intervention would “probably” be a reasonable and eff icient allocation of resources.
The work group  felt that overall, t he desirable consequences probably outweigh the undesirable
consequences in most settings due to uncertainty within the population.
Proposed Recommendation 2:
ACIP recommends vaccination* with the 2 -dose† JYNNEOS vaccine series for persons aged
12–17 years at risk for mpox §
* Interim recommendation to be revisited in 2 -3 years
† Dose 2 administered 28 days after Dose 1
§ Persons at risk:
1. Gay, bisexual, and other men who have sex with men (MSM), or a person who has sex with
MSM who in the past 6 months have had one of the following:
• A new diagnosis of ≥ 1 sexually transmitted disease
• More than one sex partner
• Sex at a commercial sex venue
• Sex in association with a large public event in a geographic area where mpox
transmission is occurring
2. Sexual partners of persons with the risks described in above
3. Persons who anticipate experiencing any of the above
Dr. Loehr asked  about background data on cost -effectiveness for resource use. He expressed
hesitanc e in making a recommendation without any sense of resource use.
Dr. Minhaj shared that, unfortunately, the work group  did not have data on the cost -
effectiveness of vaccination in the adolescent population.
Dr. Loehr noted that approximately 150 adolescents were diagnosed with Mpox during the
outbreak, but only 10 cases have been reported over the past two years. How many
adolescents would fall into that category if this recommendation were intended for those  at risk
is unclear. For adults, the estimated annual prevalence among MSM is about 3%, which
11
 translates to several hundred thousand individuals potentially at risk. However, that number is
likely much lower for adolescents. As a result, this recommendation could lead to vaccinating
tens to hundreds of thousands of individuals to prevent a very sma ll number of cases.
Additionally, the cost of the vaccine, estimated between $200 and $300 per dose, raises
concerns about the scale of resource use. This was described as a potentially extraordinary
expenditure for a relatively small public health impact.  Dr. Loehr stated that he would like much
more information about resource use before voting on this recommendation.
Dr. Brewer encouraged the work group  to align the dosing intervals, noting that
Recommendation 1 includes a one -month interval between doses, while Recommendation 2
specifies a 28 -day interval. The current adult recommendation also uses a 28 -day interval;
alignment would help ensure consisten cy. He proposed striking the phrase 'vaccination with'
from the current wording, noting that Recommendation 1 simply states 'recommend the
vaccine.' This change would help to align the two recommendations and improve cl arity for the
committee.
Dr. Brooks requested raw numbers and population -at-risk estimates. Additionally, clarification
was sought on whether the goal of a routine recommendation in the U.S. is to prevent potential
outbreaks or to protect at -risk individuals regardless of outbreak  status. Given the low number of
cases and the rarity of severe complications, questions were raised about the justification for
vaccinating a large population to prevent a relatively uncommon infection. While the rationale for
vaccination during outbreaks  is evident, further insight was requested into the work group ’s
reasoning for recommending routine vaccination now when infection is uncommon .
Dr. Minhaj noted that the recommendation to lower the age group was based on evidence that
adolescents were at risk during the 2022 outbreak. Although current case numbers are low, a
significant proportion of cases during the outbreak occurred in this popu lation. While the number
of individuals covered by the recommendation would be small, it could still help prevent mpox
cases  in this population , particularly with the increasing number of Clade I cases and the
potential for importation.
Dr. Laura  Bachman noted that estimating the exact number is challenging and requires
extrapolation from available data, such as HIV pre-exposure prophylaxis ( PrEP ) use. For
example, IQVIA data from 2021 show that approximately 6,500 adolescents were prescribed
PrEP. However, this dataset has limitations, as not all prescriptions are captured. Additionally, it
is estimated that only 15 –20% of eligible adolescents are on PrEP. As a result, determining a
precise number remains difficult.
Dr. Tracy Beth  Høeg (FDA)  thanked the presenters and highlighted concerns regarding the risk -
benefit balance of proposed Recommendation 2. It was noted that adolescents are at very low
risk for mpox, with fewer than 20 cases reported in the past year. Given the limited safety data,
including the relatively small number of vaccinated adolescents and the 315 participants in the
clinical trial, it is difficult to determine whether the benefits clearl y outweigh the potential harms.
Additionally, it was pointed out that the clinical trial excluded adolescents with significant heart
or medical conditions, which providers should consider when evaluating the safety data's
applicability to broader populations.
Dr. Agam Rao responded that a cost -effectiveness analysis was not conducted when the
recommendation was made for adults. The intent was for the vote to be revisited in a few years,
with the understanding that a cost -effectiveness analysis could be performed at that tim e.
Although fewer cases are occurring, the associated morbidity and mortality remain significant.
This recommendation was intended as an age extension of the existing adult recommendation.
It was emphasized that if these adolescent data had be en available during the adult vote, the
12
 recommendation would likely have included this population, as the perceived risk was
comparable. This clarification was provided to address questions related to the adult vote.

LYME DISEASE VACCINE
Dr. Grace Marx (CDC/NCEZID) introduced the new Lyme Disease  Vaccines  Work Group . Lyme
disease is the most common vector -borne disease in the U .S., with an estimated 476,000 cases
diagnosed and treated annually. Estimated healthcare costs for Lyme disease range from $345
million (M)  to $968 M each year.
Lyme disease vaccines were developed in the 1990s using outer surface protein A antigens
from the Borrelia burgdorferi  spirochete to prevent transmission during tick bites. LYMErixTM,
licensed by the FDA, was available from 1998 to 2002 but was discontinued due to low demand.
Since then, Lyme disease has steadily increased in the U .S., with expansion outward from  high-
incidence areas in the  Northeast, mid-Atlantic, and Midwest. New vaccines are in development,
including the protein subunit vaccine candidate  VLA15, which is now in Phase 3 trials . Several
mRNA candidates are  also in early  clinical trials.
The work group 's objectives are to review Lyme disease epidemiology, risk  of Lyme disease ,
and vaccine candidate data; assess safety, immunogenicity, efficacy, and economic analyses;
develop vaccination policy options  for ACIP consideration ; and identify data gaps.
Dr. Marx will serve as the work group  lead. The work group  chair and other members will be
announced in the coming months. The first work group  meeting is scheduled for May 2025.
Epidemiology, burden, and clinical manifestations of Lyme disease will be presented at the June
2025 ACIP meeting.

INFLUENZA VACCINES

Dr. Jamie Loehr , chair of the Influenza Work Group, introduced the session. Dr. Loehr shared
information on  the 2025 –2026  influenza vaccine composition and highlighted the importance of
the update to the A(H3N2) component. Dr. Loehr shared that the group’s presentation will
include interim vaccine effectiveness estimates for the 2024 -2025 season and an update on
self- or caregiver administration of FluMist® (available for the 2025 –2026 influenza season).
Votes on the recommendations for the 2025 -2026 season  will take place at the June 2025 ACIP
meeting.
Dr. Aaron Frutos (CDC/NCIRD) provided interim estimates of 202 4–2025 seasonal influenza
vaccine effectiveness (VE). Four networks contributed to VE estimates against laboratory -
confirmed influenza in children, adolescents, and adults across outpatient and inpatient settings:
IVY (Investigating Respiratory Viruses in the Acutely Ill), NVSN (New Vaccine  Surveillance
Network), US Flu VE Network, and VISION (Virtual SARS -CoV-2, Influenza, and Other
Respiratory Viruses Network).
For pediatrics , NVSN includes patients from outpatient clinics, emergency departments, urgent
care centers, and hospitals. The US Flu VE Network includes patients from outpatient clinics,
emergency departments, and urgent care. VISION includes patients from emergency
departments, urgent care, and hospitals. For adults , IVY includes patients admitted to the
hospital. The networks include all ages across inpatient and outpatient settings and are
geographically diverse, including patients from 23 states.
All network enrollees sought medical care for acute respiratory illness between fall 2024 and
early 2025. Each network uses a test -negative design, comparing the odds of vaccination
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 among influenza -positive cases (confirmed by molecular assay) to those testing negative for
both influenza and SARS -CoV-2. Vaccination status was determined based on receipt of any
2024 -2025 seasonal flu vaccine, using medical records, immunization registr ies, claims data,
and/or self -report.
VE was calculated as (1 -adjusted OR) × 100%. All networks adjusted for region, age, and
calendar time of illness; IVY, US Flu VE, and VISION also adjusted for sex and race/ethnicity.
VE was estimated for A(H1N1)pdm09 and A(H3N2) when data allowed. VISION did not report
subtype -specific VE due to limited data. Some estimates were excluded due to small sample
sizes or non -converging models. VE for influenza B was not estimated, as it accounted for less
than 3% of surveillance specimens.
Pediatric VE against any final influenza estimate ranged from 32% to 60% in outpatient settings
and 63% to 78% in inpatient settings. Pediatric VE against influenza A(H1N1)pdm09 estimates
ranged from 53% to 72% in outpatient settings and was 63% in the inpatient setting. In the
NVSN p ediatric VE against influenza A(H3N2) is estimated to be 42% in the outpatient setting
and 55% in the inpatient setting.  VE against H3N2 was not significant for outpatients in the US
Flu VE network, with a point estimate of 16% .
Among adults , the estimate for VE against any influenza ranged from 3 6% to 54% in the
outpatient setting and 41% to 55% in the inpatient setting. The estimated  VE against influenza
A(H1N1)pdm09 among adults  was 42% in the outpatient setting and not significant with a point
estimate of 39% in  the inpatient setting. The estimated  VE against influenza A(H3N2) among
adults  was not significant in the outpatient setting , with a point estimate of 25% and was 51% in
the inpatient setting. For adults aged ≥65  years , estimated effectiveness against any influenza
was 51% in outpatient settings  in the VISION network and not significant with a point estimate of
18% in the US Flu VE network,  and 38% to 57% in inpatient settings.
Estimates show that the 2024 –25 influenza vaccine reduced the risk of medically attended
outpatient visits and hospitalizations for influenza among children, adolescents, and adults
across 23 U.S. states. VE was effective against influenza A, with variatio n by subtype and
network.   These results were published in MMWR in February 2025.
Dr. Joshua Quint (California DPH) presented on the study of interim influenza vaccine
effectiveness estimates a gainst laboratory -confirmed influenza  in California, October 2024 –
January 2025.
Recent changes in California’s reporting have expanded public health data sources, allowing VE
analyses across various age groups and settings using electronically reported vaccination and
testing records. Since  June 2023, negative influenza test results have been reportable to the
state’s electronic communicable disease reporting ; positive  results have been reportable since
October 2019 .  These  data are submitted electronically by laboratories across the state.   All
influenza vaccination records are now re portable to CAIR, the state’s immunization registry .
At the end of the 2023 -24 season, the California team  compared their interim VE estimates to
those from CDC’s other VE platforms . Despite differences in populations and systems, the
estimates were remarkably similar. For children ages 6 months to 18 years, VE was 56%, falling
within the confidence intervals  for nearly all the CDC platforms.
A case -control (test -negative) design was used, classifying those who tested positive for
influenza as case patients. The analysis covered October 1 , 2024,  to January 31, 2025, and
included California residents aged ≥6 months with a molecular or culture influenza test reported
to the state’s electronic lab system. Participants were considered vaccinated if they had at least
one documented dose of seasonal fl u vaccine in the immunization registry ≥14 days before
testing. The earliest positive or negative tes t (if no positives) was used for individuals with
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 multiple test results. Labs with weekly positivity rates >50% were excluded due to data quality
concerns, accounting for <5% of total tests. VE was calculated as (1 − adjusted OR) × 100%,
using a mixed -effects logistic regression model adjusted for continuous age, race/ethnicity,
testing week, a nd county as a random effect.
Weekly flu  activity in California peaked in late December with approximately 17,000 positive test
results and remained high through January.  In total, 85% of positive specimens were influenza
A, and 7% were type B.
Among samples tested by public health laboratories, the predominant subtypes were H3 (53%)
and H1 (43%). Only 300 influenza B samples were lineage typed, so those results are limited.
Only about 5% of all tests are subtyped by public health labs, and these may overrepresent
severe cases.
Of 591,000 samples meeting eligibility criteria, 23% were positive for influenza and 77% were
negative. Vaccination rates were 17.6% among positive cases and 25.9% among negative
controls.
The median age of cases  was 30 years compared to 43 years for controls. Race distribution
was similar, though cases were 5 percentage points more likely to be Hispanic and 7
percentage points less likely to be white.
Adjusted VE against lab -confirmed influenza was 44.7% overall (95% CI: 43.7 to 45.6). By age
group , the following estimates were calculated : 0-18 years , 50%; ages 1 9 to 49  years, 46%;
ages 50 to 64  years,  39%; and ≥65 years , 39%. VE against influenza A was 42% overall, while
VE against type B was higher at 71%. Among subtyped cases, VE was 47.9% for H3N2 and
49.5% for H1N1.
For children ages 2 to 17  years , the estimated VE for live attenuated influenza vaccine (LAIV)
was 61% compared to 48% for those who received another vaccine type. These rates were
45% and 52% in the previous season. Median ages were similar across groups.
Cumulative VE estimates showed early -season variability with wide confidence intervals. VE
peaked at 55% in early December before declining to about 45% by the end of the study period.
Monthly analysis showed the highest VE in November at 56%, followed by a decrease in
December and January, when confidence intervals were narrowest.
Type -specific monthly VE remained high for influenza B at approximately 75% in December and
70% in January, in contrast to the decreasing pattern observed for influenza A.
Limitations included incomplete documentation and reporting of vaccination and testing; inability
to assess partial versus full vaccination status for children under 9 years; lack of information on
symptoms, test setting, and outcomes such as illness, hosp italization, or death; incomplete and
potentially biased reporting of influenza subtypes; and lack of control for confounding factors
such as health -seeking behavior and pre -existing conditions.
Dr. Quint summarized that the data indicate that current influenza vaccines protect against
laboratory -confirmed influenza in individuals aged ≥6 months. VE was higher for influenza B and
among younger age groups, but vaccination offered protection across all ages. This study also
highlights how expanded and improved public health data systems can be used to generate
timely, in -season VE estimates.
Dr. Shaw inquired whether there is any information on VE against H3N2 in older adults.
Dr. Quint responded that this season's CDC’s VE estimates do not yet include H3N2 -specific
data for older adults. However, this information is routinely estimated each year, and final
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 estimates from networks that include older adult populations will be available at the end of the
season.
Dr. Asturias requested data on the timing of immunization and illness to help determine whether
the observed decline in VE for influenza A types is related to waning immunity over time or
specific strain effects.
Dr. Quint shared that the group did not include vaccination timing in the model. Still, it could be
inferred that the decline in VE toward the end of the season is likely related to earlier
vaccination timing.
Dr. Zhu added that the group has a manuscript under peer review that examines explicitly
waning immunity and overall VE estimates. While the group has not closely analyzed waning for
this season yet, the trends are expected to be like those observed in pre vious seasons.
Ms. Moser requested clarification on whether the comparison group consisted solely of
unvaccinated children or included those who received the inactivated influenza vaccine.
Dr. Zhu shared that for the pediatric LAIV analysis, approximately 455 children were vaccinated
with LAIV. The control group for this comparison consisted of unvaccinated children. A similar
control group was used for children who received non -LAIV vaccine s, meaning unvaccinated
children served as the comparison group for both analyses. While the population was stratified
by vaccine type, a similar  unvaccinated group was used as the reference for each VE
calculation.
Ms. Moser inquired whether all four VE networks were still funded to collect data throughout this
season and next.
Dr. Ellington confirmed that three of the four networks will continue active data collection during
the 2025 –2026 season. However, the IVY Network is planned to sunset and will not contribute
data for the next flu season.
Dr. Cineas asked whether there was a data breakdown for VE estimates by vaccine type (for
example, high dose) and age group, specifically for patients ≥65  years  of age.
Dr. Frutos shared that there is no data at this time, and Dr. Zhu also shared that the group does
not have those estimates available yet. However, product -specific VE was calculated for the
previous season, and those estimates will be available soon.
Dr. H øeg asked whether potential bias was accounted for in the test -negative design studies
presented , for example , based on the likelihood of seeking testing .
Dr. Frutos stated that one of the key strengths of the platforms and networks used to estimate
vaccine effectiveness each year is that both influenza -positive and influenza -negative
individuals have acute respiratory illness. Since estimates are based on medically attended
influenza rather than all infections, the potential bias from differ ences in testing behavior is
considered minimal. The estimates are believed to be accurate.
Dr. Kuril la inquired whether there has been any attempt or consideration to estimate VE
stratified by whether individuals had a prior  season flu infection and/or had received a flu
vaccine.
Dr. Frutos responded that while the group did not account for this in the interim estimates, it is
regularly examined and will be included in upcoming analyses.
Dr. Allyn Bandell (AstraZeneca) shared the details of FluMist  for self- or caregiver
administration , which was licensed by the FDA last fall  and will be available for the upcoming
2025 -2026 season . FluMist for self- or caregiver administration will be  available for home
16
 delivery. It expands access by allowing individuals or caregivers to administer it at home , with
ordering  through an online pharmacy service and using screening that aligns with that used in a
traditional pharmacy setting .
FluMist builds on the growing acceptance of in -home healthcare. This flexibility can help
overcome common barriers like busy schedules. A recent modeling study by the University of
Pittsburgh found that increasing flu vaccination coverage in children ages 5 to 17  years of age
using caregiver -administered FluMist could reduce symptomatic flu cases across all age groups.
This approach helps prevent missed school and work and may reduce the spread of flu at home
and in schools.
Step-by-step instructions, developed through a human -factors usability study, ensure ease of
use. The online pharmacy service, FluMist Home, supports vaccine ordering, delivery, and
documentation. A return shipment program is provided to guide proper dispo sal after use.
Several studies have evaluated the effectiveness, immunogenicity, reactogenicity, and safety of
self- and caregiver -administered FluMist. A study of over 4,500 adults found no significant
differences in effectiveness, immunogenicity, or adverse events betw een self -administered and
healthcare -administered FluMist. Reactogenicity was also comparable. A Department of
Defense study involving more than 1,000 adults found no variation in immunogenicity by
administration method. Mean geometric titers for influenza  A were comparable (p = 0.43), and
local/systemic reactogenicity events were similar. In a study of caregiver administration  to
children aged 2. 6 to 17 years , all doses were successfully given. Adverse events were mild, and
some caregivers noted they would not have been able to vaccinate without the home option.
AstraZeneca conducted an FDA -required human factors usability study to inform the
instructions for use and packaging. The goal was to ensure intended users could administer
FluMist safely and correctly, avoiding common errors like underdosing or incorrect
administration. Participants reflected the target population, including a mix of male and female
participants, right/left handedness, a range of education al levels, and with and without
experience with nasal sprays. Results showed that 100% of users succes sfully administered the
full dose and understood the instructions.
The final packaging and instructions used in the human factors study were submitted to the FDA
in the supplemental BLA. When the FluMist package is opened, patients see a n instruction
sheet that provides information on  storage, administration, and disposal. It guides users step -
by-step, from inspecting the package to administering one spray per nostril, using plain
language and visuals. It also addresses common concerns like nasal dripping and includes
guidance  on proper disposal .
The online pharmacy service, FluMist Home, supports patients who want to administer FluMist
at home. It's important to note that AstraZeneca and A SPN (the pharmacy partner) are following
standard roles for vaccine manufacturers and pharmacies. AstraZeneca will manufacture and
supply the vaccine, develop educational and awareness campaigns, and provide support for
FluMist -related questions. A SPN will manage the FluMist Home service, including eligibility
screening, dispensing, delivery, and pharmacist counse ling. A SPN pharmacists will also follow
state -specific regulations for determining patient eligibility, issuing prescriptions, and
documenting FluMist administration in immunization information systems based on the shipping
address.
Persons ordering the vaccine will  receive text notifications with the delivery time; no signature is
required. Inside the package is a sheet listing the contents, storage instructions, the Vaccine
Information Statement, and a QR code linking to how -to videos. FluMist should be refrigerated
17
 until use. Delivery is timed to ensure proper temperature and handling through two -day delivery
services. Patients will receive  texts until the vaccine administration is confirmed.
Upon receipt of confirmation of vaccination, vaccination data is entered into the state
immunization system using the same process used by  retail pharmacies. The pharmacy can
send records to the patient’s physician, and patients can also download their vaccination record
from the portal to share with their provider. This mirrors standard retail pharmacy practices.
FluMist packaging includes a return shipment program for safe disposal of the used sprayer,
which is considered medical waste. A prepaid, pre -labeled envelope is provided, so there is no
need to visit the post office. The envelope holds multiple sprayers a nd can be placed in a home
mailbox. A medical waste company handles tracking and proper disposal.
Dr. Asturias asked what happens if a patient experiences an adverse event at home, how it
would be reported, and who would be responsible for the patient.
Dr. Bandell shared that patients can access instructions  in the package and online . If they
experience an adverse event, they can report it through the A SPN pharmacist by email or chat,
directly to AstraZeneca, or through VAERS. This process mirrors existing practices in the retail
pharmacy setting , similar to other medications used at home.
Dr. Cineas asked whether the usability studies included non -English speakers and inquired
about plans to develop materials in Spanish and other languages.
Dr. Bandell explained that the usability study primarily included individuals whose first language
was English. However, Spanish -language support is planned for next season. The package
insert is already available in Spanish, and A SPN Pharmacy offers online and customer support
for Spanish speakers this year. Additional Spanish -language resources and broader language
support are planned for future rollout. Other languages are to follow.
Dr. Chen requested clarification on the recommended temperature range and the 12 -hour out -
of-refrigerator limit.
Dr. Bandell responded that the temperature range is the same as in clinical settings, typically
between 35 and 4 5 degrees Fahrenheit. Most household refrigerators in the U.S. fall within this
range, and this information is clearly communicated to the consumer  multiple times.
Dr. Zucker requested clarification on IIS reporting, specifically whether there is a step for
attestation or verification that the vaccine was administered by the patient or caregiver after it is
shipped to the household and before the pharmacy reports the  dose to the registry.
Dr. Ami Patel (ASPN) responded that before reporting to the IIS, the pharmacy follows up with
the patient or caregiver to confirm that the vaccine was administered. The dose is not reported
until confirmation is received.
Dr. Zucker sought confirmation that, given the over 50 state immunization registries, a system
will be in place to report to each registry.
Dr. Patel explained that they are contracting with a widely used reporting vendor, commonly
utilized by retail pharmacies, to ensure nationwide connectivity and reporting to all jurisdictions.
They have already begun contracting with the company and buildi ng the connections, with plans
to complete testing before September, when the first reporting is expected.
Ms. Lyons asked whether there are any anticipated issues with state laws related to linking to
an IIS through an online pharmacy rather than a pharmacy with a physical location in that state.
18
 Dr. Patel acknowledged that some states require a physical location within the jurisdiction to
report to their IIS. They plan to work directly with those IIS programs to determine how best to
comply with local requirements.
Ms. Lyons followed up to ask whether a mechanism was available to offer FluMist to a younger
child.
Mr. Leone explained that pharmacy laws vary by state, and those differences will be integrated
into the system’s modeling. For example, suppose a child is under a certain age, such as under
seven, and state law prohibits pharmacy administration for that ag e group. In that case, the
system will block the request and prompt the user to seek vaccination in a traditional setting. He
emphasized that FluMist will still be available in traditional healthcare settings, and individuals
ineligible through the service  will be encouraged to consult their pediatrician or healthcare
provider.
Ms. Moser noted that compliance in the trials appeared to be strong and asked about the
mechanisms in place for follow -up beyond text messaging. She also inquired about plans for
handling the return or disposal of unused vaccine, whether this is expected t o be a significant
issue, and how it is being addressed.
Dr. Bandell explained that the returns program was designed to be as simple and convenient as
possible. All materials are preprinted and pre -labeled; the package can be placed directly back
in the mailbox. Multiple sprayers can be included in the return. S he added that there is no
expectation that compliance with the return process will be an issue.
Ms. Moser clarified that she was concerned about unused or unwanted vaccines.
Dr. Patel clarified that, for safety reasons, they cannot accept returns once the product has been
dispensed. Patients would be instructed to dispose of the unused vaccine in the same manner
as a used dose .
Dr. Loehr asked whether it would be possible to distinguish self -administered from provider -
administered FluMist in immunization registries and whether there would be a clear indicator for
that distinction.
Dr. Bandell confirmed that this distinction can be made and noted that the NDC numbers for
self-administered and healthcare -administered FluMist are different. This allows immunization
registries to identify the method of administration through the NDC cod e.
Dr. Loehr raised the issue of handling situations when a child does not receive the full vaccine
dose, such as when the child moves, the spray misses the nose or is accidentally sprayed on
the cheek. He sought clarification on how parents should manage obt aining another dose in
these cases.
Dr. Patel explained that the patient or caregiver can contact the pharmacy to report what
happened in such situations. The pharmacy would handle the appropriate reporting to VAERS,
work with the patient’s insurance to obtain a second dose through available overrides and
ensure the replacement dose is spaced four weeks apart.
Dr. Loehr commented that many individuals must provide proof of flu vaccination, and questions
often arise about whether self -administered doses at home are sufficient. It was noted that
determining the acceptability of home administration is the responsib ility of the hospital or
organization, not the manufacturer. Suppose a hospital decides not to accept home dosing. In
that case, that decision lies with the institution, and it would not be reasonable to expect the
manufacturer to develop a system to meet the specific requirements of different organizations.

19
  COVID- 19 VACCINES

Dr. Robert Schechter (ACIP, Work Group  Chair) introduced  the COVID -19 Vaccines W ork
Group.  In August 2024, the Food and Drug Administration authorized and approved  the 2024 -
2025 COVID -19 vaccines:
• Moderna COVID -19 vaccine* in persons ≥6 months
• Novavax COVID -19 vaccine** in persons ≥12 years
• Pfizer -BioNTech COVID -19 vaccine* in persons ≥6 months
*Omicron JN.1 lineage, KP.2 strain
**Omicron JN.1 lineage, JN.1 strain

ACIP  recommen ds everyone aged ≥6 months should receive 2024 –2025 COVID -19
vaccination .
• Children aged 6 months –4 years may need multiple doses of COVID -19 vaccines to be
up to date, including at least 1 dose of 2024 –2025 COVID -19 vaccine
• People aged 5 –64 years should get 1 dose1 of 2024 –2025 COVID -19 vaccine
• People who are ≥65 years2 and people ≥6 months of age with moderate or severe
immunocompromise3 should receive a second dose  of 2024 –2025 COVID -19 vaccine 6
months after their first 2024 –2025 dose (minimum interval of 2 months)
• People with moderate  or severe immunocompromise may receive additional doses of
2024 –2025 COVID -19 vaccines under shared clinical decision -making (minimum interval
of 2 months)
1. People who are unvaccinated and receive Novavax COVID -19 vaccine for initial vaccination should receive 2 doses of
2024 –2025 Novavax COVID -19 vaccine
2. People who are unvaccinated and receive Novavax COVID -19 vaccine for initial vaccination should receive 2 doses of
2024 –2025 Novavax COVID -19 vaccine followed by a third dose of any 2024 –2025 COVID -19 vaccine dose 6 months
(minimum interval 2 months) af ter the second dose.
3. If previously unvaccinated or receiving initial vaccination series, at least 2 doses of 2024 –2025 vaccine are recommended,
and depending on vaccination history more may be needed. This additional 2024 –2025 vaccine dose is recommended 6
months (minimum i nterval 2 months) after completion of initial vaccination series.
From October 2021 to March 2025, provisional weekly COVID -19 death data reported to the
CDC show  a consistent decline in deaths each year. In the first three years, there were typically
two surges annually: a larger winter surge followed by a smaller late summer or fall surge. In
2025, the winter surge was smaller than the summer/fall surge in 2024, indicating a potential
shift in the seasonal pattern.  Over the past four years, similar patterns in hospitalizations have
emerged, with the winter peak being la rger than the late summer/fall peak, but as seen with
COVID -19 deaths,  the winter surge in early 2025 was smaller than the summer/fall surge in
2024.
COVID -19 illness levels have declined compared to previous years , while the 2024 -2025
influenza season was more severe than the 2023 –2024 season. As a result, estimates for
illnesses, outpatient visits, and hospitalizations are higher for influenza than for COVID -19.
Despite this, death estimates are similar for both diseases, reflecting a  higher likelihood of
severe outcomes from a case of COVID -19.
Vaccination coverage for the 2023 –2024 and 2024 –2025 formulations remained low. By spring,
cumulative coverage for adults aged ≥18 years  reached only about 20% in both years. This
indicates that most  adults, including those at higher risk for severe outcomes, remain
unimmunized.
20
 The work group  has considered  risk-based and universal recommendations for the 2025 –2026
COVID -19 vaccines.  In the spring, the FDA's Vaccines and Related Biological Products
Advisory Committee is expected to meet to discuss and recommend strain selection for the
2025 –2026 COVID -19 vaccines. ACIP will review and vote on the recommended use at its June
meeting. V accine availability is anticipated in late summer or early fall.
Dr. Bishoy Rizkalla (Moderna) provided an overview of Moderna’s next -generation  COVID -19
vaccine, mRNA -1283, in individuals ≥12 Years of Age . COVID -19 remains a leading cause of
hospitalization among respiratory viruses in the U .S. Risk factors for severe COVID -19 infection
include advancing age and pre -existing chronic conditions.

The next -generation COVID -19 vaccine, mRNA -1283, is designed to offer stronger protection,
especially for those most at risk. Unlike current vaccines that use the full spike protein, mRNA -
1283 targets only the N -terminal and receptor -binding domains, which  trigger strong immune
responses. This streamlined approach shortens the mRNA sequence and allows for a lower 10 -
microgram dose , one-fifth of the original. It also positions mRNA -1283 as a strong candidate for
future combination vaccines like Moderna’s inv estigational flu -COVID vaccine, mRNA -1083.

Study 301 is a Phase 3 study assessing the safety, immunogenicity, and efficacy of mRNA -
1283. It  is a randomized, blinded Phase 3 trial with participants aged ≥12 years. They were
randomly assigned to receive either mRNA -1283 or mRNA -1273 (commercially known as
Spikevax®). Both of these vaccines  were bivalent vaccines targeting the original SARS -CoV-2
strain and the Omicron BA.4/5 variants, in line with 2023 vaccine recommendations.

Demographics and baseline characteristics were balanced between groups. Half of the
participants had a chronic condition linked to a higher risk of severe COVID -19 outcomes, as
defined by the CDC. Prior SARS -CoV-2 infection and time since the last COVID -19 vaccination
were also similar between groups.

Safety was monitored through a median follow -up of 8.8 months. There were no imbalances in
adverse events between the vaccine groups. No cases of myocarditis or pericarditis were
reported among mRNA -1283 recipients, and no safety concerns were identified.

mRNA -1283 elicited a higher antibody response at Day 29 compared to Spikevax. The highest
BA.4/BA.5 neutralizing antibody geometric mean ratio (GMR) at Day 29 was observed in adults
aged ≥65 years. mRNA -1283 consistently produced higher antibody responses  compared to
Spikevax  over time in this age group. Neutralizing antibody responses against Omicron
XBB.1.5, observed in a separate study, were similar between mRNA -1283 and Spikevax.

Prespecified success criteria for relative vaccine efficacy were met , with an estimated relative
efficacy of 9.3%  for mRNA -1283  compared to Spikevax  in preventing CDC -defined COVID -19.
In adults, efficacy increased with age, reaching a point estimate of 13.5% in those aged ≥65
years. Among adolescents, immune responses were comparable between the two vaccines,
supporting similar protection, though est imates were less precise due to a smaller sample size
and lower case numbers. Overall, efficacy findings wer e consistent with earlier immunogenicity
results, with adults aged ≥65 years showing the highest neutralizing antibody levels and the
greatest estimated efficacy. Relative vaccine efficacy was favorable for mRNA -1283 among
individuals with comorbidities an d in preventing severe COVID -19.

Dr. Rizkalla summarized that mRNA -1283 was generally well tolerated , and no safety concerns
were identified. The study met its primary noninferiority endpoints for immunogenicity and
21
 relative efficacy compared to Spikevax. Although the study was designed to demonstrate
noninferiority, results showed higher immune responses among older adults and a trend toward
greater efficacy with advancing age and among individuals with chronic conditions linked to
severe COVID -19. This vaccine has the  potential to reduce the COVID -19 burden, especially
among those most vulnerable to severe outcomes . The anticipated  Prescription Drug User Fee
Act (PDUFA ) date is by the end of May, with plans to offer mRNA -1283 for COVID -19
prevention this fall using an updated formulation aligned to circulating SARS -CoV-2 variants
recommended by the FDA.

Dr. Asturias asked whether using one -fifth of the antigen dose in the new vaccine formulation
might be a better strategy, considering the existing natural or vaccine -induced immunity in most
of the population. He noted that, as seen with other vaccines, bo osting with a lower dose can
sometimes be more effective than using a traditional high dose.

Dr. Rizkalla responded that it  has been well established that the receptor binding domain and
the N -terminal domain contain key epitopes critical for generating neutralizing antibodies and
cell-mediated immune responses. Clinically, mRNA -1283 has shown that, even at a fraction of
the d ose, it can produce higher neutralization levels  compared to spike -based antigen designs.
A broad range of clinical and nonclinical studies has evaluated this construct across multiple
variants, including the original SARS -CoV-2 strain, Beta, and Omicron variants such as BA.1,
BA.4/5, XBB.1.5, as well as more recent variants like JN.1 and KP.2. Across all studies, mRNA -
1283 consistently outperformed Spikevax  in inducing neutralizing antibodies. This strong
correlation between neutralizing antibody response and protection is further supported by
efficacy data, reinforcing mRNA -1283 as a robust vaccine design.

Dr. Shaw inquired about the single fatal event reported in the Spikevax group. He also asked
whether there were any imbalances in prior COVID -19 infection or vaccination history between
the groups, as both can affect immune responses.

Dr. Rizkalla explained that they conducted sensitivity analyses to assess responses based on
the number of prior COVID -19 vaccine doses. These analyses looked at both immune response
and efficacy. The findings showed that mRNA -1283 consistently induced hig her immune
responses compared to Spikevax, regardless of how many prior doses an individual had
received. This translated into consistent efficacy results  that aligned with the primary analysis .
There were no fatal events in the mRNA -1283 investigational v accine group. One fatal event
occurred in the Spikevax group involving a 77 -year-old female with a history of cardiovascular
disease. The death occurred suddenly within a week of vaccination. The investigator
determined the event was unrelated to the vacci ne and most likely due to the individual’s
underlying cardiovascular condition.

Dr. Cineas questioned whether the study population, which included individuals with multiple
comorbidities, also included immunocompromised patients.

Dr. Rizkalla clarified that immunocompromised individuals were not included in the study.
However, it is expected to perform at a comparable level because mRNA -1283 shares a
common platform with Spikevax and shows similar immune responses .

Ms. Moser noted the encouraging potential for higher and more durable immune responses in
older adults . She asked  for comments on the similar rates of adverse events, despite the lower
dose of the newer vaccine.

22
 Dr. Rizkalla commented that both vaccines induce strong immune responses, so differences in
systemic adverse events would not necessarily be expected. He noted a trend toward fewer
local reactions with mRNA -1283, which may be explained by its lower dose an d smaller
injection volume: 10 micrograms in 0.2 mL for mRNA -1283 compared to 50 micrograms in 0.5
mL for Spikevax.

Dr. Kamboj asked whether there were any comparisons of T -cell responses between mRNA -
1273 and mRNA -1283.

Dr. Rizkalla responded that T -cell responses were evaluated in the Phase 2 study, comparing
mRNA -1283 at the Phase 3 dose to mRNA -1273 (Spikevax). The findings showed comparable
CD4 and CD8 T -cell responses between the two vaccines, with responses persisting through
the 366 -day duration of the study.

Dr. Schechter asked whether it would be possible to get a more detailed age breakdown for
myocarditis risk, specifically within the 18 to 30 or 18 to 40 years age range. Referring to slide
six of the presentation, which grouped data for adolescents and then adults aged 18 to 64
years , the request was made to see sample sizes and risk data for younger adults who may
have been at higher risk for myocarditis in the trial.

Dr. Rizkalla noted that no myocarditis or pericarditis were observed throughout the program and
offered to return to the work group  with a breakdown of demographics for the 18 years and older
population.

Dr. H øeg raised a question about how the efficacy of Spikevax was determined in the context of
a noninferiority study comparing it to mRNA -1283. Given the high level of underlying population
immunity from prior infection, there was interest in whether the comparis on relied on real -world
data, which can be affected by healthy vaccine bias, or on neutralizing antibodies, which have
not been clinically validated in individuals with prior infection. The question focused on how
efficacy, particularly against out comes like hospitalization, COVID -19-related death, and long
COVID, was assessed for Spikevax to evaluate the relative performance of mRNA -1283.

Dr. Rizkalla responded that the Phase 3 study was comparing the relative vaccine efficacy
between the two arms, based on CDC -defined COVID -19.

Dr. H øeg asked how Moderna could determine the efficacy of mRNA -1283 if we don’t know
what the efficacy of what it Is being compared to.

Dr. Edwards explained that each season, as the strain composition of the Spikevax product is
updated, vaccine effectiveness is measured throughout that season. This process helps
establish and continuously update the vaccine effectiveness profile for each variant
composition, including the one used in the current trial.

Dr. Fiona Havers (CDC/NCIRD)  provided updates on COVID -19–associated  hospitalizations .
The trends described are based on data from COVID -NET, a population -based surveillance
system that tracks  laboratory -confirmed COVID -19 hospitalizations. COVID -NET covers  about
10% of the U.S. population. It includes data from over 300 hospitals in 98 counties across 13
states. Hospitalizations are included if a positive SARS -CoV-2 test was reported within 14 days
before or during admission, with testing based on clinical  judgment and facility policy. Basic
demographic data is collected for all cases, while detailed clinical data are gathered from a
stratified random sample.
23

COVID -19 hospitalization rates have shown both winter and summer peaks, unlike RSV and
influenza, which typically peak only in winter. For the 2024 –2025 season, COVID -19
hospitalization rates are lower than the previous season ; since the beginning of the COVID -19
pandemic,  many hospitalizations have occurr ed outside the typical respiratory virus season.
Since the 2021 –2022 peak, rates have declined across all age groups. Hospitalization rates
vary by age group and virus, with the highest rates observed in infants aged <6 months and in
older adults . In the 2023 –2024 season, adults aged ≥75 years continued to experience the
highest cumulative hospit alization rates of any adult age group.

During the 2024 –2025 season, children and adolescents made up about 4% of COVID -19–
associated  hospitalizations. Pediatric hospitalization rates were highest in infants aged <6
months. Children  aged <5 years had higher influenza and COVID -19-associated  hospitalization
rates than school -aged children and adolescents (aged 5 –17 years ). For children ≤4 years,
COVID -19 hospitalization rates during the 2022 –2023 and 2023 –2024 seasons were similar to
those for influenza. Among children aged 5 –17 years , COVID -19 hospitalization rates were
lower than influenza during the same seasons.  Between October 2022 and April 2024, older
children  hospitalized with COVID -19 were more likely to have underlying medical conditions
than younger age groups. About 1 in 5 hospitalized children and adolescents with COVID -19
were admitted to the ICU. Fewer than 5% of eligible hospitalized children and adole scents had
received the most recently recommended COVID -19 vaccination.

Dr. Havers summarized that pediatric COVID -19-associated hospitalization rates are highest
among the youngest age groups. Among school -aged children, hospitalization rates are
generally higher for influenza than for COVID -19. More than half of children and adolescents
hospitalized with COVID -19 had multiple underlying conditions, with the proportion increasing
with age. Additionally, most hospitalized children had not received the most recently
recommended COVID -19 vaccine during the 202 3–2024 seasons.

Adults aged ≥65 years account for more than two -thirds of all COVID -19–associated
hospitalizations among adults. Hospitalization rates increase with age, and in recent years,
adults aged ≥65 years have consistently had higher COVID -19 hospitalization rates than those
for influenza. The risk of COVID –19–associated  hospitalization is also elevated among
community -dwelling adults aged ≥18 years with underlying medical conditions. About 1 in 5
adults hospitalized with COVID -19 were admitted to the ICU. Most adults hospitalized  during the
2023 -2024 season had not received a COVID -19 vaccine since September 2022. Furthermore,
as of November 30, 2024, only 30% of nursing home residents had received the 2024 –2025
COVID -19 vaccine.

Dr. Havers summarized that COVID -19 hospitalization rates are highest among the oldest age
groups, with adults aged ≥75 years accounting for about half of all adult hospitalizations. While
overall hospitalization rates have declined over time, adults aged ≥75 years continued to have
the highest rates in the most recent season with complete data, surpassing all other adult age
groups, even compared to previous seasons. The risk of COVID -19 hospitalization also persists
during the summer months. Most hospital ized patients had not received the most recent
COVID -19 vaccine before admission. Chronic kidney disease, diabetes, and coronary artery
disease were associated with an increased risk of hospitalization across all adult age groups.
The relative risk of hosp italization among adults with vs. without select medical conditions
generally declined with increasing  age for most, but not all, conditions  examined .

24
 Dr. Ruth Link -Gelles (CDC/NCIRD) shared interim estimates of the effectiveness of the 2024 –
2025 COVID -19 vaccine . These findings reflect the added benefit of vaccination in a population
with widespread vaccine  and infection -induced immunity. Vaccine coverage was similar in the
2023 -2024 and 2024 -2025 seasons for all adults but slightly higher among older adults during
the 2024 –2025 season. Coverage reached just under 25% for adults aged ≥18 years and
approximately 41% to 47% for older age groups.

VE is measured by comparing the frequency of health outcomes in vaccinated versus
unvaccinated individuals. During the monovalent COVID -19 vaccine rollout, absolute VE was
used, focusing on differences between vaccinated and unvaccinated groups. During the  bivalent
period, relative VE was used to compare outcomes between recipients of different vaccine
types. For the 2024 –2025 COVID -19 vaccines, VE is measured using a combined approach,
comparing disease rates in those who received the 2024 –2025 vaccine to those who did not,
regardless of prior vaccination or infection. This method is similar to how seasonal influenza VE
is typically assessed.

The first VE platform is the VISION Network, a multi -site system that uses electronic health
records from over 300 emergency departments  and urgent care centers,  and more than 200
hospitals. VISION uses a test -negative design and includes eligible adults with COVID -like
illness and a clinical test within 10 days before and 72 hours  after their healthcare visit. The
analysis includes adults aged ≥18 years with COVID -like illness. Cases are defined as those
with a positive nucleic acid amplification test ( NAAT) or antigen test for SARS -CoV-2 and no
positive test for RSV or influenza. Controls are those with a negative N AAT test for SARS -CoV-
2 and no positive test for influenza or RSV, depending on age. Vaccination status is determined
using electronic health records and state and city immunization registries.

The second VE platform is the IVY Network, a multi -site system in 26 hospitals across 20 U.S.
states. Like VISION, it uses a test -negative design with active enrollment , including  patient
interviews and swab collection. Participants were adults aged ≥65 years hospitalized with
COVID -like illness. Cases had a positive NA AT or antigen test for SARS -CoV-2, while controls
tested negative for SARS -CoV-2, influenza, and RSV by RT -PCR. Vaccination history is
determined through electronic medical records, state and  local vaccine registries, and self -
report. Specimens are collected for central testing and sequencing.

Among adult s, the 2024 –2025 COVID -19 vaccination provided additional protection against
COVID -19–associated  emergency department and urgent care visits, as well as
hospitalizations, compared to no 2024 –2025 vaccine dose. The vaccine also offered protection
against COVID -19–associated  hospitalizations among adults aged ≥65 years with
immunocompromising conditions.

Dr. Link -Gelles reminded the committee  that VE should be interpreted as the added benefit of
2024 –2025 vaccination in a population with high levels of infection -induced immunity, vaccine -
induced immunity, or both. While prior SARS -CoV-2 infection contributes to protection, that
protection wanes over time. Increased SARS -CoV-2 circulation in late summer 2024, just before
the vaccine’s approval, may have r aised population -level immunity against JN.1 -lineage strains,
potentially resulting in lower measured VE than in a population with less recent i nfection.

Questions and comments on Dr. Havers and Dr. Link -Gelles’s presentations were taken
together

25
 Dr. Asturias commented that he was encouraged by the increased focus on children,
emphasizing the need to dispel the myth that young children are not at risk for severe COVID -
19 or hospitalization. He noted that the data shows that hospitalization trends in children are not
decreasing. With new cohorts of unprotected infants born each year, current recommendations
may need to be adjusted to highlight the importance of vaccinating young children. He pointed
out that 70% of pediatric hospitalizations occur in  children under four years of age, and half of
these cases involve children without underlying medical conditions. He stressed the importance
of recognizing children as a priority group that needs stronger protection than they currently
receive.

Dr. Loehr requested clarification on how chronic kidney disease was defined in the analysis,
noting its strong association with severe COVID -19. He asked whether the definition was based
on creatinine clearance and whether it included class 3 or class 4 kidney disease.

Dr. Havers  clarified that the relative risk of chronic kidney disease may be slightly overestimated
in this analysis due to the data collection methods used in the Behavioral Risk Factor
Surveillance System (BRFSS), which relies on self -reported information. This co uld affect the
accuracy of the denominator and potentially skew the results. While there is a real increased
risk associated with chronic kidney disease, comparing its magnitude to other underlying
medical conditions can be challenging. Chronic k idney disease is identified through medical
chart review for COVID -NET hospitalizations , without strict diagnostic criteria, whereas BRFSS
relies on self -reported conditions.
Dr. Kamboj asked whether any updated data have shown an improved uptake of additional
COVID -19 vaccine doses among immunocompromised patients nationwide. A second question
focused on slide 13, noting the limited sample size. While it was understandable tha t the data
were not sufficient to assess the time since vaccination, Dr. Kamboj inquired whether the
number of doses was examined in any way.
Dr. Link -Gelles responded that additional doses were examined, and overall, uptake has been
low within the VISION population (and nationally). Due to the timing of the analyses, few
individuals were eligible for a second or subsequent dose during the study  period. It was noted
that they will continue to monitor this throughout the rest of the year.
Dr. H øeg commented that noting 90% of children hospitalized with COVID -19 were
unvaccinated does not provide meaningful insight into vaccine effectiveness, given that nearly
90% of children in the general population are also unvaccinated , most recently 87%, and 86%
the year before. The same consideration applies to adults. It’s important to account for the
baseline vaccination rate in the population when interpreting these findings.
Dr. Havers clarified that the slide showing the vaccination status of hospitalized children was not
intended to reflect VE. For VE data, reference was made to the approach and findings
presented by Dr. Link -Gelles. Children were not included in those VE an alyses due to lower
baseline disease rates , but monitoring will continue throughout the year. Dr. Link-Gelles  added
that the design of VE studies allows for adjustment based on baseline vaccination coverage,
using the unvaccinated population as the referen ce group to compare the rate or risk of disease
in vaccinated versus unvaccinated individuals.
Dr. Naima Joseph (ACOG) highlighted the high rate of COVID -19 hospitalization in young
children, particularly among infants aged <6 months who are not eligible for vaccination.
Previous CDC data have shown especially high rates in this group. Small studies have
suggested that boo sting during pregnancy may help protect these infants through maternal
26
 immunization. Dr. Joseph expressed interest in seeing further data on the effectiveness of this
approach.
Dr. Havers emphasized that the presentation primarily focused on children and infants older
than six months. However, it is correct that for pediatric age groups, hospitalization rates are
highest among infants aged <6 months, who rely on maternal vaccination during pregnancy for
protection. Dr. Havers acknowledged this as an important point not previously highlighted in the
discussion.
Dr. Lakshmi Panagiotakopoulos (CDC/NCIRD) shared the work  group’s considerations for the
2025 –2026 COVID -19 vaccines. These include whether to maintain the current multi -dose initial
series for children aged <5 years and for immunocompromised individuals, and whether to
continue a universal recommendation for eve ryone aged ≥6 months or move to a risk -based or
hybrid approach. The group is also evaluating guidance for those recommended to receive
more than one dose per year, including adults aged ≥65 years a nd people aged ≥6 months  who
are immunocompromised.

The CDC’s list of conditions that increase the risk of severe COVID -19 is extensive and largely
based on pre -Omicron  data. Researchers used multiple data sources and regression modeling
to estimate how many U.S. adults have the conditions on this list.  The analysis found that risk of
having any condition increases with age, and about 74% of adults aged ≥18 years or older have
at least one high -risk condition. Of note, s ome conditions  from the list , such as Parkinson’s
disease, physical inactivity, and stero id use, were not included  in the analysis, so the actual
percentage is likely higher.

As of the 2024 –2025 season, JN.1-lineage strains remain  the predominant circulating variants
of SARS -CoV-2. COVID -19 hospitalization and death rates have declined overall, though rates
remain highest among adults aged ≥65 years. Pediatric COVID -19 hospitalizations were lower
than those for influenza and RSV du ring the 2024 –2025 season and lower than the previous
year. COVID -19 also dropped in rank as a leading cause of death , from 8th to 12th in children
between 2021 and 2023  and from 3rd to 10th in adults between 2021 and 2023. During the
period September 2023 through August 2024, almost 90% of the deaths due to COVID -19 in the
U.S. were among adults aged 65 years and older.  Among children under 1 year, COVID -19
caused more deaths than influenza, while for those aged 1 –17 years , influenza led to more
deaths. Vaccine coverage remained stable, with a slight increase among adults aged ≥65  years ,
and vaccine effectiveness in adults held steady  between 2023 –2024 and 2024 –2025 .
Cumulative hospitalization rates continue to decline  since 2021 . By the end of 2022,
approximately 90% of children aged ≥2 years , 82% of children aged 1 -2 years,  and 64% of
infants under 1 year of age had been infected with SARS -CoV-2. Looking at U.S. blood donors,
higher exposure through infection and vaccination led to increased SARS -CoV-2 antibody
levels, though gains diminished after 4 or more  exposures. In 2023, an estimated 9.2 million
adults and 0.3 million children in the U.S. reported  having had  long COVID. Vaccination reduced
the risk of long COVID by up to 72% in children and up to 63% in adults, depending on
symptom type. The incidence of multisystem inflammatory syndrome in children ( MIS-C) fell
significantly, from 6.8 to 0.08 cases per 1 million person -years between the pre -Delta period and
2024. Although most children with MIS -C in 2023 and 2024 were vaccine -eligible, few were
vaccinated, and most had received their last dose more than 12 months before illness onset.

An increased risk of myocarditis was observed following COVID -19 vaccines during 2020 –2022,
particularly after the primary series and first booster doses. No increased risk has been detected
in the VSD or in VAERS  during the 2022 –2023, 2023 –2024, or 2024 –2025 seasons to date.
Myocarditis following COVID -19 vaccination typically resolves quickly, and cases are associated
27
 with less severe cardiovascular outcomes compared to myocarditis following COVID -19
infection or conventional myocarditis.

The work  group discussed concerns that shifting from a universal to a risk -based COVID -19
vaccine recommendation could reduce coverage among people with high -risk conditions.
Influenza vaccination coverage among adults with high -risk conditions increased slightly a fter
the universal recommendation in the 2010 –2011 season, though the trend was already rising
and plateaued shortly afterward. Hepatitis B vaccination coverage among adults with risk factors
remained below pre -pandemic levels following the univer sal recommendation in 2022. By 2023,
coverage for adults universally recommended for zoster vaccination was approaching that of
pneumococcal vaccination among high -risk adults, despite longstanding recommendations for
pneumococcal vaccination. It remains u nclear how shifting from a universal to a risk -based
recommendation would impact COVID -19 vaccine coverage.

The work  group reviewed parental vaccine confidence data to better understand barriers to
COVID -19 vaccine uptake among children, given that vaccination rates for children aged 6
months to 17 years remain low , at around 12%, similar to last year. Only 22% of parents said
they were very likely to vaccinate their child against COVID -19 to prevent respiratory illness,
which was lower than other prevention options  offered in the survey . Among parents whose
children had previously received one dose of the COVID -19 vaccine, most maintained the same
confidence level  in the vaccine’s safety and effectiveness, though 15% reported less
confidence. In contrast, a bout 45% of parents whose children had never received a COVID -19
vaccine reported decreased confidence in vaccine safety and effectiveness  compared to when
the vaccines first became available. Parents of children who received at least one COVID -19
vaccine dose were more likely to have already received or plan to receive the 2024 –2025
vaccine for their child than  those whose children had never been vaccinated. When asked why
they did not vaccinate their child, parents of never vaccinated children were more likely to cite
concerns about safety, effectiveness, and potential side effects. Additionally, 15% of parents
whose children had received a prior dose believed their child had already received enough
COVID -19 vaccine doses.

The work  group reviewed COVID -19 booster recommendations from other countries for
individuals who have completed an initial vaccine series. Most countries recommend boosters
for older adults every 6 to 12 months , with age cutoffs ranging from 50 to 80 years. For
otherwise healthy adults, the U .S. is the only country with a routine recommendation; other
countries either have no recommendation, discretionary recommendations , or recommendations
based on pregnancy status. Most countries recommend yearly vaccina tion for high -risk adults.
For immunocompromised adults, most countries recommend vaccination every 6 to 12 months,
with the U.S. being the only country that permits additional doses beyond two per year. Routine
vaccination of healthy children is not widely recommended outside the U.S. and Canada
(Canada has a discretionary recommendation in this group) . The UK, Canada, and the U.S.
recommend annual vaccination for high -risk children , while Australia and the WHO do not. For
immunocompromised children, most countries recommend vaccination every six months , with
the U.S. being the only country that permits additional doses beyond two per year .

As of February 13, 2025, after reviewing updated data on hospitalization risks, mortality trends,
vaccine coverage, hesitancy, and myocarditis, the majority of the work  group supported a risk -
based recommendation for 2025 –2026 COVID -19 vaccination. Most members who favored a
non-universal policy supported a risk -based approach by conditions and exposures, a universal
recommendation for certain age groups, and permissive l anguage to allow anyone seeking
protection to receive the vaccine. Additional data on v accine effectiveness, seroprevalence, long
28
 COVID, vaccine coverage, and MIS -C were presented, and the group received feedback from
liaison organizations. These organizations raised concerns about implementation,
communication, confidence, and equit able access  under a risk -based recommendation. After a
follow -up poll on April 3, the majority still supported a risk -based approach. Most members
selecting a non -universal policy again supported risk -based recommendations by condition or
exposure, universal recommen dations for certain age groups, and perm issive access for those
seeking vaccination.

Dr. Jamieson expressed concern about moving to a risk-based COVID -19 vaccine
recommendation, noting that 74% of adults have risk factors and that COVID -19 remains a
leading cause of death among both adults and children. There was skepticism about the
effectiveness of risk -based strategies in the US, and hepatitis B was viewed as an unsuitable
comparison. Instead, influenza was seen as a more relevant example, with concern that
decoupling flu and COVID -19 vaccinations could create confusion as people are just beginning
to understand the importance of recei ving both annually. Additional concerns included
challenges with implementing a permissive recommendation, particularly regarding healthcare
financing and access. Based on the information presented, support was expressed for
maintaining a universal recomme ndation.

Dr. Loehr expressed support for considering a risk -based COVID -19 vaccine recommendation
and appreciated that it is being taken seriously. Concerns were raised about the data showing
that over 70% of adults aged 18 to 50 years are considered at risk, which did not align with
clinical experience. The estimate seemed reasonable for older adults but appeared too high for
those under 50  years of age . While in favor of the risk -based approach, there was concern
about its feasibility and the message it may send, especially given that COVID -19 remains a
significant public health issue with thousands of hospitalizations and deaths.

Dr. Asturias emphasized the importance of identifying data that could help protect young infants
and children from COVID -19, noting that this group has not received adequate attention.
Updated information on the transfer of maternal antibodies was highlighted as particularly
useful, as most existing data come from earlier in the pandemic when protection was less
certain. With many women now  vaccinated or previously infected, current data on maternal
antibody transfer would be valuable. Additional details on hospitalizations among children in
their first year of life were requested , particularly the causes. Based on influenza data showing
that young children are often hospitalized for fever and irritability, it would be interesting to see
the causes of these hospitalizations.

Dr. Brooks emphasized the need for additional data, specifically requesting modeling on long
COVID. While COVID -19 rates may be low among healthy individuals in their 30s, the potential
for developing long COVID remains a concern. Even with a lower risk of long COVID , the
absolute number of cases could still be significant. The primary concern was the long -term
impact of long COVID, especially in younger age groups that may not receive a vaccination
recommendation. Modeling the absolute number of long COVID  cases in these groups was
identified as an important data need.

Dr. Brewer addressed concerns about implementing a risk -based COVID -19 vaccine approach,
noting that while it's commonly believed  that such strategies are less effective, there is no clear
evidence to support that conclusion. Although the idea has been discussed for years and
shared by various groups, the data does not definitively show that risk -based approaches are
less effective than universal ones. Based on the information reviewed, there was a shift in
29
 perspective, with the view that the belief in the limitations of risk -based strategies is not currently
supported by strong evidence.

Ms. Moser expressed support for exploring a risk -based COVID -19 vaccine recommendation
and emphasized the importance of including the youngest children in those considerations.
Echoing a previous point, it was noted that young children represent a newly su sceptible group
each year . Vaccinating  them could help reduce hospitalization rates for those under one year
old and potentially protect them from long COVID on their first exposure. While evidence on
long COVID in this age group is still developing, early  vaccination may also help avoid concerns
previously associated with vaccinating adolescents, such as myocarditis. In a separate
comment, appreciation was expressed for the public comments  submitted for the meeting,
particularly regarding the change in licensure  status for Novavax  that was anticipated to happen
a few weeks ago . While acknowledging that this issue falls under FDA jurisdiction and not the
committee’s, a request was made for an update from the FDA ex officio  to address public
interest, given that the  topic was not listed on the current agenda.

Dr. H øeg responded that while it is unclear to what extent an update can be provided at this
time, a public update on the matter will be released very soon.

Dr. Fryhofer shared a perspective as a practicing internal medicine physician who sees many
older and medically fragile patients  and expressed concern for very young children as a new
grandparent. Reflecting on the data showing that 74% of individuals have at least one risk
factor, the point was made that, in practice, simplicity is key. The "keep it simple" approach was
emphasized, pa rticularly given that most adult vaccinations are administered in pharmacies.
Risk-based recommendations can be challenging in these settings as they often require patients
to self -report medical conditions or pharmacists to review medication histories, which some
patients may be uncomfortable with. As a member of the COVID -19 vaccine work  group and
one of the 19% who supported a universal recommendation, Dr. Fryhofer explained that these
concerns contributed to that position.

Dr. Loehr responded to a previous comment by referencing data from the pneumococcal
vaccine work group , noting that uptake for the risk -based recommendation in adults aged 50 to
65 years was around 20%, compared to approximately 65% for the age -based recommendation
in those aged 65 years and older. This was presented as evidence that risk -based
recommendations may result in lower vaccine uptake. While still supportive of a risk -based
approach, it was emphasized that this difference in coverage should be con sidered.

PNEUMOCOCCAL VACCINES

Dr. Miwako Kobayashi (CDC/NCIRD) shared the proposed plan on behalf of the Pneumococcal
Vaccines Work  Group. The group's term of reference is to review evidence to inform the use of
new pneumococcal conjugate vaccines in U .S. adults and children.

Over the past 40 years, the U .S. pneumococcal vaccine program has undergone multiple
updates, with several occurring in the last five years. During this period, three new
pneumococcal conjugate vaccines were licensed for use. The most recent was the 21 -valent
pneumococcal conjugate vaccine (PCV21) for adults, which was licensed last year.

The work group acknowledges gaps  in current pneumococcal vaccine recommendations for
pregnant women. This gap is highlighted in the adult immunization schedule, which shows there
30
 is currently no guidance for using  pneumococcal vaccines in pregnant women  with underlying
conditions or risk factors that increase the risk of pneumococcal disease.

Additionally, ACIP has never specifically voted on pneumococcal vaccine use among
hematopoietic stem cell transplant recipients. Clinical guidance for pneumococcal vaccine use
was last updated in 2023 following the licensure of 15-valent pneumococcal conjugate vaccine
(PCV15 ) and 20-valent pneumococcal conjugate vaccine ( PCV20 ). Currently, there is no
guidance on using  PCV21 for this group.

Since a formal literature review on pneumococcal vaccine use in pregnant women and
hematopoietic stem cell transplant recipients has not been presented to ACIP, the work  group
has been conducting such a review. A summary of the findings and proposed language for
updated clinical guidance will be presented for the committee’s review and feedback at the June
2025 ACIP meeting.

HUMAN PAPILLOMAVIRUS (HPV ) VACCINES

Dr. Oliver Brooks (ACIP, Work Group  Chair)  introduced the Human Papillomavirus (HPV)
Vaccines Work Group. HPV causes cancers of the cervix, vagina, vulva, penis, anus, and
oropharynx. The HPV vaccine offers long -lasting protection against the types most likely to
cause cancer. In the 19 years since its introduction, the vaccine has shown high efficacy in
clinical trials , high population impact in real -world settings, and stro ng herd effects of
vaccination programs.
The HPV Vaccine s Work Group, previously active for many years, had been inactive since
2019. It was re constituted  and began meeting monthly in July 2024. The group gave its
returning presentation to ACIP at the October 2024 meeting.
In the U.S., HPV vaccination recommendations include routine, catch -up, and shared clinical
decision -making.
• Routine vaccination is recommended at ages 11 –12 years  and can start at age  9 years .
• Catch -up vaccination is recommended through age 26 years for those not adequately
vaccinated earlier.
• Shared clinical decision -making is recommended for adults aged 27 –45 years who are not
vaccinated.
The number of HPV vaccine doses depends on the age at which  the series is started:
• 2 doses are recommended if the series begins before the 15th birthday.
• 3 doses are recommended if the series begins at age 15 years or older, or for individuals
with immunocompromising conditions.
The work  group is reviewing two policy issues. The first is the wording of the recommended age
for routine HPV vaccination. Some stakeholders support starting at age 9  years , which aligns
with current ACIP recommendations.  The work  group is also reviewing the recommended
number of HPV vaccine doses in light of growing evidence supporting fewer doses. It is
evaluating data on 2 doses for individuals aged ≥15 years and 1 dose for individuals aged ≥9
years.
In 2022, the World Health Organization recommended a 2 -dose HPV vaccination schedule for
individuals aged ≥9  years , with a 1 -dose option for those aged 9 –20 years . Although low - and
middle -income countries were expected to adopt the 1 -dose schedule first, early adopters
included the UK and Australia. Some countries did not move to a 1 -dose schedule but shifted
31
 from 3 to 2 doses for individuals aged >14  years . Regional advisory groups including those in
PAHO and the WHO African Region support the 1 -dose recommendation. As of April 2025, 67
countries have adopted a 1 -dose schedule for some age groups, and 77 countries have
adopted a 2 -dose schedule.
Dr. Carla DeSisto (CDC/NCIRD) began with an overview of the work group’s policy questions:
• Should 1 dose of HPV vaccine be used for prevention of HPV infection and HPV attributable
disease, instead of the currently recommended vaccination schedule?*
• Should 2 doses of HPV vaccine be used for prevention of HPV infection and HPV
attributable disease, instead of the currently recommended vaccination schedule?†
*There are two populations under review for this question. For individuals aged 9 –14 years, the
comparison is 1 dose versus the currently recommended 2 doses. For those aged ≥15 years, the
comparison is 1 dose versus the currently recommended 3 doses.
†The population for with question i s persons aged ≥15 years , and the comparison is 2 doses versus the
currently recommended 3 doses.
There is no plan to change the recommendation of shared clinical decision -making for persons
aged 27 -45 years, although the number of recommended doses in this age group may change.
The four critical outcomes are HPV-associated cancers, precancers, serious adverse events
related to vaccination, and incident persistent HPV infection.  The six important outcomes are
prevalent HPV infection, incident HPV infection, immunogenicity, anogenital warts, low -grade
histological abnormalities, and recurrent respiratory papillomatosis.
For the systematic literature review , Cochrane reviewed global literature on reduced -dose HPV
vaccination schedules in 2022. This review was adapted to the U.S. context, and the literature
search was updated to include publications from 2022 to 2024.  The literature review included 37
publications, which represent 16 studies. These publications include recently published updates
from the Costa Rica Vaccine Trial (CVT), the IARC -India trial, and the Dose Reduction
Immunobridging & Safety Study (DoRIS).
In the Costa Rica Vaccine Trial (CVT), women aged 18 –25 years were randomly assigned to
receive 3 doses of either the bivalent HPV vaccine or a control  vaccine . Some received fewer
doses due to factors like pregnancy or missed visits, with reasons balanced across groups. The
data are being evaluated as a cohort study by the number of doses received. At the October
ACIP  meeting, data on protection against prevalent infection and immunogenicity through year
11 were reviewed.  Sixteen years after vaccination, H PV 16/18 seropositivity remained very high
at >98%  in both the 1 -dose  and the 3 -dose groups ; as expected the geometric mean antibody
concentratio n was lower in the 1-dose group . During years 11 –16 post -vaccination, small but
statistically significant declines in antibody levels were observed in women who received either
1 or 3 doses.
In the IARC -India trial, unmarried girls aged 10 –18 were randomly assigned to receive either 2
or 3 doses of the quadrivalent HPV vaccine. A ministerial decree halting vaccination in trials
resulted in cohorts receiving 1, 2, or 3 doses. Cervical screening with an HPV test began at age
25 for married participants, and age - and site -matched unvaccinated married women were
recruited as controls. At the October  ACIP  meeting, data on protection against persistent
infection through 10 years were reviewed.  In their November 2024 publication, the authors
reporte d a median follow -up time of 12 years and a total study duration of 15 years, with
participants aged 25 to 33 years. VE against persistent HPV 16/18 infection was 92% with 1
dose, 94.8% with 2 doses, and 95.3% with 3 doses. Confidence intervals for these e stimates
overlapped. No CIN2+ cases associated with HPV 16/18 were detected among vaccinated
32
 participants, compared to eight cases among unvaccinated women. No cases of invasive
cervical cancer related to HPV 16/18 were reported in the study.
In the DoRIS trial from Tanzania, girls aged 9 –14 were randomly assigned to receive 1, 2, or 3
doses of either the  bivalent  or 9-valent  HPV vaccine. All participants were followed for 36
months, and those in the 1 - and 2 -dose groups were invited to join a long -term extension. The
primary outcome was to assess noninferiority of HPV 16/18 -specific seropositivity after 1 dose
compared with 2  or 3 doses of the same vaccine. The trial also included a co -primary
immunobridging objective to demonstrate noninferior ity of HPV 16/18 antibody geometric mean
concentrations  (GMCs ) after 1 dose, compared with that seen following 1 dose in efficacy
studies. At the October ACIP meeting, data on immunogenicity and immunobridging to KEN
SHE through two years were reviewed . The update focused on the 9-valent HPV  vaccine, which
is the vaccine currently used in the United States. For HPV 16, 100% of girls in both the 1 -dose
and 2 -dose groups were seropositive  five years after vaccination . For HPV 18, 93% were
seropositive in the 1-dose group and 98% in the 2 -dose group. Although seropositivity was high,
noninferiority for HPV 18 was not met.  Regarding GMCs, the 1 -dose titers were lower than the
2-dose titers, as expected. In the 1 -dose group, titers plateaued at month 12 and remained
relatively stable through month 60. In the 2 -dose group, titers declined after peaking at month 7.
Of the 59 studies identified by the Cochrane  literature review , 49 were excluded due to a
serious risk of bias. All excluded studies were observational. Key biases included differences in
infection risk at vaccination, differences in HPV exposure during follow -up, and dose timing.
These biases likely result in lower effectiveness with fewer doses. To address bias, researchers
used buffer periods, stratifying results by age at vaccination or restricting the population to
younger ages , adjustments for sexual activity and sociodemographic factor s, and stratifying
results for 2 doses by the interval between first and second doses.
Only one observational study with less than serious risk of bias , which provided data on a
critical outcome,  was identified  in the updated systematic review . The Wu -Sweden study
followed 2.2 million females aged 10 –35 years  from 2006 to 2022. Using linked registries,
CIN2+ outcomes were assessed by  the number of 4-valent HPV vaccine doses  received .
Adjusted Poisson models with a 12 -month buffer were used, with median follow -up times of 8.4
years (unvaccinated) and 12.4 years (vaccinated).  Among girls who in itiated vaccination before
age 15, the authors observed incidence rate ratios ( IRRs ) of 0.42 after 1 dose, 0.54 after 2
doses, and 0.50 after 3 doses. The overlapping confidence intervals suggest no significant
difference in CIN2+ risk by number of doses.  In women who initiated vaccination after age 21
years , only those who received 3 doses had a statistically significant IRR. While the comparison
was to unvaccinated females and does not directly align with  the work  group’s policy questions ,
the study provi des a useful example of observational data on effectiveness by number of doses.
There are several outstanding questions for reduced number of HPV vaccine doses. The
longest efficacy data came from the IARC -India study (15 years post -vaccination), and the
longest immunogenicity data came  from the Costa Rica trial (16 years). No data exist on
protection at sites other than the cervix. Of the 16 studies, 13 included only females. There are
no efficacy data on males for reduced -dose schedules, and some evidence suggests lower
antibody titers in adolescent males compared with females after one dose. Data are also very
limited for immunocompromised individuals , and l imited data exist on efficacy and
immunogenicity in older age groups .
Dr. Ruanne Barnabas (Harvard University) shared the results for the KEN SHE trial. The study
found that the single -dose HPV vaccination is highly efficacious, with 98% vaccine efficacy for
HPV 16/18. Results are broken into 36 -month and 54 -month periods .
33
 The 36 -month results come from the randomized phase of the study, which included a control
group. Women aged 15 –20 years were recruited from three clinical trial sites in Kenya and
randomly assigned to one of three groups: immediate 9-valent HPV vaccination ; immediate
bivalent HPV vaccination ; or a control group receiving meningococcal vaccination.  The study
endpoint was incident persistent vaccine  type-specific infection among HPV-naïve participants
at vaccination. This is important, as HPV vaccines have n o therapeutic effect.
Participants were followed for 36 months. For the per -protocol analysis, those with evidence of
infection at enrollment or month 3 were excluded to allow for a buffer period. Cervical swabs for
HPV DNA were collected every six months to assess persistent i nfection.  Participants with
prevalent HPV infection at enrollment were excluded from the per-protocol /modified intention -to-
treat analysis, because the vaccine is prophylactic only.
After three years, single -dose HPV vaccine efficacy remained high and durable (VE  98% for
HPV 16/18 and VE  96% for HPV 16/18/31/33/45/52/58). Based on sustained antibody levels
over 16 years, the group hypothesized that single -dose vaccination would be effective and
durable over 54 months .
At month 36, participants in the KEN SHE study were crossed over while maintaining the study
blind to assess the durability of HPV vaccination. Those who  had initially received the HPV
vaccine were given meningococcal vaccination, while those who had received meningococcal
vaccine were crossed over to receive the 9-valent HPV vaccine.
To evaluate the effectiveness of single -dose HPV vaccination among individuals aged 18 –23
years , researchers compared the cumulative incidence of persistent HPV infection using
Kaplan -Meier curves and incidence rate estimates for the immediate and delayed vaccine
groups. Vaccine efficacy was analyzed as a function of time since vaccination using a Cox
regression model that accounted for time and time -varying covariates to assess durability . The
primary endpoint was incident persistent vaccine -type specific HPV infection, measured at two
time points six months apart.
There were no differences in baseline characteristics between study groups. At cross -over
vaccination, participants were 18 –23 years old. Retention was 90% for three or more swabs,
and the median time between endpoint swab collection was 6.00 months. HPV exposure to non -
vaccine types was consistent across the study and all groups. Therefore, the only difference
between the three groups was the vaccine received at randomization.
Participants vaccinated with the bival ent vaccine at age 18 –23 years had similarly low rates of
incident persistent HPV 16/18 infection compared to vaccination at age 15 –20 years. HPV 16/18
vaccine efficacy, VE  99.2% (95% CI 96.1 -99.9%), was sustained over time without evidence for
waning immunity. Participants vaccinated with the 9 -valent vaccine at age 18 –23 years had
similar rates of incident persistent HPV 16/18/31/33/45/52/58 infection compared to vaccination
at age 15 –20 years. HPV 16/18/31/33/45/52/58 vaccine efficacy, VE  98.9% (95% CI 94.9 -
99.8%) , was sustained over time without evidence for waning immunity.
Dr. Barnabas summarized that s ingle -dose HPV vaccination effectively protected adolescent
girls and young women from incident persistent HPV infection over the first 54 months post -
vaccination. The study’s rigorous design, high protocol adherence, high retention, and clear
outcome ascertainment provide strong  evidence of single -dose vaccine efficacy for individuals
up to age 23  years . Efficacy against HPV types 16/18 and the seven high -risk types showed a
lower confidence interval bound  above 94%, consisten t with licensure trials for 3 doses, with no
evidence of waning protection. Exploratory analyses from the intention -to-treat population found
high protection once prevalent infections at vaccination had cleared.
34
 Ms. Cassandra Pingali (CDC/NCIRD)  shared the data summary for the 2023 National
Immunization Survey -Teen (NIS -Teen). NIS-Teen  includes a two -phase process: a random digit
dialed phone survey of parents of teens aged 13 to 17 years and a follow -up mailed survey to
vaccination providers  (e.g., clinics, pharmacies, health departments)  if permission is granted.
The provider data  includes vaccination dates, types, and doses. Coverage estimates are based
on provider -reported data. In 2023, the survey included 16, 568 teens born between January
2005 and December 2010.
Coverage with ≥1 Tdap and ≥1 MenACWY has been high and stable since 2018. However,
coverage with ≥1 HPV vaccine and proportion of HPV up to date is lower compared to most
other routine vaccines.
In 2023, 89 .0% of adolescents aged 13 to 17 years had received a Tdap vaccine, 88.4% had
received a MenACWY vaccine, 76.8% had received an HPV vaccine, and 61.4% were up to
date on HPV vaccination.  This marks the second consecutive year HPV vaccination coverage
has not increased among adolescents aged 13 to 17 years.
In 2023, about 77% of adolescents received an HPV vaccine. The HPV vaccine is commonly
given with other recommended adolescent vaccines, with 69.5% receiving it with one or more
additional vaccines in one visit. Among those who received an HPV vaccine, 47.8% received it
with both the Tdap and MenACWY vaccines in one visit.
The percentage of adolescents who were HPV up  to date  was lower in mostly suburban and
mostly rural areas compared to mostly urban areas. There were no differences in MSA status
between the Tdap and MenACWY vaccinations .
Overall, vaccination coverage was lower among uninsured adolescents compared to those with
private insurance across all vaccines. Adolescents with "other" insurance also had lower up-to-
date HPV  rates than those with private insurance. Coverage was similar between adolescents
with private insurance and those with Medicaid, including for the HPV vaccine.
HPV vaccination has historically been higher among Medicaid -insured adolescents compared to
those with private insurance, as observed from 2015 to 2021. However, in 2022, coverage with
one or more doses declined by three percentage points among Medicaid -insured adolescents.
As a result, in 2022 and 2023, HPV vaccine coverage was similar between Medicaid -insured
and privately insured adolescents.
Historically, Black and Hispanic adolescents have had higher coverage with ≥1 HPV vaccine
than White adolescents . In 2023, only Hispanic adolescents had higher coverage.  In 2023,
coverage with ≥1 MenACWY was higher among Asian adolescents compared to White
adolescents.
In 2023 , coverage with ≥1 dose of the HPV vaccine was 77%  in the United States.  Mississippi
had the lowest coverage (60%), and Rhode Island had the highest coverage with ≥1 HPV
vaccine (93%).  HPV vaccine initiation at ages 9 –10 and 11 –12 has increased from 2018 to
2023, while initiation at age 13 –17 has decreased from 2018 to 2023.
Dr. Pingali summarized that in 2023, 76.8% of adolescents had initiated the HPV vaccine, and
61.4% were up to date. This was the second consecutive year without increased coverage,
which remains lower than for Tdap and MenACWY vaccines. Most adolescents began the HPV
vaccine series at ages 11 to 12, and 47.8% received the HPV, Tdap, and MenACWY vaccines
in a single visit. HPV vaccination coverage continues to vary by sociodemographic factors,
health care access, and state.
35
 Ms. Moser acknowledged the value of the NIS -Teen and NIS -Child  data in showing national
vaccination progress . A question was raised about whether data collection will continue or if any
recent changes have impacted the ability to gather this information.
Dr. Pingali confirmed that, as far as is known, data collection for both the NIS -Teen and NIS -
Child surveys is continuing.
Dr. Asturias asked whether there are differences in age at HPV vaccine initiation by geographic
region in the U.S.
Dr. Pingali noted that the sample size is likely too small to analyze HPV vaccine initiation among
the youngest age group, ages 9 to 10  years , as less than 5% of the national sample initiated at
those ages. However, it may be possible to examine state -level data to see if stable estimates
and differences can be identified.  It was also shared that the group can look at initiation rates
among adolescents aged 13 to 15 years to identify patterns or differences.
Dr. Brooks requested clarification on the “up to date” definition in the slide showing data over
time from 2015 onward. Specifically, the question was whether "up to date" included individuals
aged 9 to 14 years who only needed two doses, as the slide also referenced those with greater
than or equal to three doses.
Dr. Pingali clarified that in NIS -Teen, HPV up  to date is defined as receiving  three or more
doses, or two doses if the first dose was given before age 15  years , with at least 5 months
minus 4 days between the first and second dose.
Dr. Schechter asked whether there was any evidence of disruptions or delays in vaccine
administration among adolescents aged 13 to 17 years during the pandemic, similar to effects
seen with other vaccines or age groups. There was also a question about the recent
equalization of HPV vaccination rates between Medicaid -insured and privately insured
adolescents, whether this trend reflects catch -up among privately insured adolescents, a decline
among those with Medicaid, or a combination of both.
Dr. Pingali explained that vaccination coverage dropped notably among children born in 2008,
who would have been 12 years of age  during the pandemic. This group appeared to be the
most affected. The 2009 birth cohort, who were 11 years of age in 2020, showed fewer
disruptions, and the 2010 cohort , the youngest in the 2023 data, had coverage levels similar to
pre-pandemic levels, except for a drop in HPV up -to-date coverage. Regarding the equalization
in coverage between Medicaid -insured and privately insure d adolescents, there was a 3
percentage point drop in HPV coverage from 2021 to 2022 among Medicaid -insured teens.
While the cause is not entirely clear, there is speculation that changes in access to the  VFC
program or other pandemic -related factors may have contributed.
Dr. Jane Kim (Harvard University) shared estimates of the expected  impact of single -dose HPV
vaccination on the health of the U.S. population. T wo independently developed mathematical
models were adapted to the U.S. population to project the long -term health impact of single -
dose HPV vaccination  (Harvard and HPV -ADVISE) . The models accounted for historical HPV
vaccination coverage . They were  used to explore key uncertainties related to the efficacy and
duration of protection from a single dose at the population level.
The Harvard and HPV -ADVISE  models are individual -based HPV transmission models that
account for herd immunity and reflect multiple birth cohorts by age and sex. They share similar
structures but differ in key areas. Both models  include the seven high -risk HPV types in the 9-
valent vaccine, but Harvard groups other types, while HPV - ADVISE  models them separately.
Harvard models transmission by monthly partnership duration, while HPV - ADVISE  uses
36
 transmission per sexual act. HPV - ADVISE  also includes an additional CIN1 health state not
captured in the Harvard model.
Both models overestimate the number of lifetime partners compared to U.S. data, suggesting
higher assumed HPV exposure, especially in older age groups. This assumption is important
when evaluating the potential waning of protection from a single -dose HPV vaccine.
Vaccine assumptions were based on existing clinical trial data, including the KEN SHE trial. The
base case assumed 98% efficacy for one dose, indicating noninferiority to two doses. A worst -
case scenario used 90% efficacy, reflecting the lower bound of pub lished KEN SHE data. For
the duration, the base case assumed lifelong protection, matching that of two doses. The worst -
case scenario assumed an average duration of 25 years  (normally distributed with standard
deviation of 5 years) , with waning starting at  15 years post-vaccination for some individuals and
no protection for most by 40 years post -vaccination. Both efficacy and duration were assumed
to be the same across all vaccine -targeted HPV types.
Results showed that with 2 -dose or noninferior 1 -dose 9 -valent HPV vaccination, the model s
project near elimination of HPV -16 infections and an approximately  90% reduction in cervical
cancer by the year 2070. Under the worst -case assumption  of vaccine efficacy (90%), 1 -dose
vaccination is projected to produce  similar population -level impacts as  2-dose or noninferior 1 -
dose.  Even with waning 1 -dose  protection (average of 25 years),  1-dose vaccination is
projected to  produce similar population -level impacts as 2 -dose or noninferior  1-dose.  Assuming
both lower VE (90%) and  waning 1 -dose protection (average  25 years), 1-dose vaccination is
projected to produce  a slight rise in  HPV incidence (~2045) and cervical  cancer incidence
(~2060).  All scenarios result in similar  reductions in HPV  16 and cervical  cancer incidence over
time.
Compared to previously published results, the average vaccination age  in the current  analysis is
at least five years later. With a 25 -year duration, waning occurs when individuals are less
sexually active. This means a higher percentage remains directly protected at older ages,
leading to stronger indirect  effects even as protection from one dose declines .
Dr. Kim concluded that the model s suggest switching to  a 1-dose HPV vaccination in the U.S.
would result in similar reductions in HPV and cervical cancer incidence as continuing with two
doses  in the U.S.  Even under pessimistic assumptions about vaccine efficacy and duration, the
model s project only limited increases in HPV infections and cervical cancer cases. This is
because the switch would occur when HPV prevalence is already low, and most individuals
would remain protected during peak sexual activity, providing both direct and indirect  protection.
Continued monitoring of 1 -dose protection is important to detect any signs of waning and apply
mitigation strategies if needed. Under pessimistic assumptions, switching back to a 2-dose
vaccination could help recover potential losses in cancer prevention ; mitigation strategies would
not require revaccinating those who received one dose to be successful . The consistent results
from two independent models add strength to these conclusions.
Dr. Asturias noted that while immunogenicity and efficacy of the HPV vaccine have consistently
been strong, regardless of the number of doses, the key driver of the model’s population -level
impact appears to be the indirect effects, such as herd immunity. He asked for confirmation that
the broader impact is less about the individual immune response and more about how many
people are protected overall, which ultimately drives the population -level outcomes.
Dr. Kim confirmed that this is correct, emphasizing that strong indirect or herd effects from HPV
vaccination are already being observed in the U.S. population. While direct protection is
important, it also contributes to broader population resilience by protecting unvaccinated
individuals through indirect  effects.
37
 Dr. Brooks asked whether the modeling accounted for a potential delay in detecting a rebound
in HPV infections or cervical cancer cases , leading to delay in initiating mitigation efforts .
Dr. Kim responded that any potential rebound in HPV prevalence would likely be identified
through clinical trial data before it becomes evident in epidemiologic trends. Ongoing trials
monitor  long-term vaccine efficacy, which helps detect early signs of waning. As shown in
previous modeling published in the Journal of the National Cancer Institute , any rebound in HPV
infections would occur several years later, with cervical cancer cases appearing even further
down the line. If needed, mitigation strategies such as reverting to a 2 -dose schedule could be
implemented in time to offset potential losses in health outcomes.
Dr. Ruth Stefanos (CDC/NCIRD) reviewed the modified EtR framework. Given interpretation
issues on the HPV vaccination schedule, the policy question  is:
Should the ACIP recommendations state:
HPV vaccination is routinely recommended at age 9 –12 years
instead of:
HPV vaccination is routinely recommended at age 11 or 12 years; vaccination can be given
starting at age 9 years
For the public health problem, Dr. Stefanos shared that HPV is the most common sexually
transmitted infection in the U.S. Persistent infection can lead to precancers and cancers. An
estimated 37,800 HPV -attributable cancers are diagnosed each year in the U S.
HPV vaccination coverage has increased since its introduction, but it still lags behind other
adolescent vaccines. NHANES data show that quadrivalent HPV type prevalence among
sexually experienced females aged 14 to 24 years in the U.S. dropped from 18.5% in 2003 to
2006, the pre -vaccine era, to 2.8% in 2015 to 2018. This represents an 85% reduction. Similar
declines were observed among sexually experienced females across different racial  and ethnic
groups.  Declines in cervical precancers have been seen in women aged 20 -24 years since 2008
and in women aged 25 -29 years since 2016. Cervical cancer has been declining for several
decades in the U.S., due to cervical cancer screening which allows for detection and treatment
of precancers before progression to ca ncer. Continued declines in cervical cancer in women
aged 21 -24 years are likely a combination of both changes in screening recommendations and
vaccination impact.
The CDC estimated the annual direct medical costs of HPV -attributable disease in 2020 U.S.
dollars, published in 2023. The total yearly  cost is $9.01 billion, with $4.05 billion attributed to
treatment expenses.
The work group felt that HPV -related disease is of public health importance.
For the benefits, Dr. Stefanos explained that changing the wording for the routine HPV
vaccination age to 9 –12 years  could offer greater clarity and flexibility. However, potential harms
include the risk of separating the HPV vaccine from the broader adolescent platform, or at least
creating the perception of doing so, and possible pushback from providers who prefer to
vaccinate at age 11  years , as well as from some parents for various reasons.
Although ACIP currently allows vaccination starting at age 9  years , the wording has confused
some partners. Changing the recommendation to state ages 9 –12 years clearly would improve
clarity. Some providers want to begin vaccination at age 9, but electronic health records often
do not prompt vaccination at age 9  due to the current wording. Updating the language could
help address this issue and support those aiming to start vaccination earlier.
38
 In Clinical Decision Support for Immunization ( CDS i) resources, the minimum age for HPV
vaccination is 9 years, and the earliest recommended age is currently 11  years . Additionally,
there is administrative guidance included in the CDSi resources that state the vaccination can
be given starting at age 9 years.
While some systems reflect this in their prompts, most clinical decision support tools use the
earliest recommended age to trigger alerts. As a result, prompts for HPV vaccination typically
begin at age 11. Changing the wording of the routine vaccination recommendation to ages 9 –
12 years would update the earliest recommended age to 9 in CDSI tools, prompting HPV
vaccination starting at age 9.
The policy under consideration is to change the recommended age wording to 9 –12 years, not
to set a new recommendation specifically for ages 9 –10 years . A review was presented to ACIP
in October. It found that starting HPV vaccination at ages 9 –10 years was associated with
higher series completion by age 13 compared to starting at 11 –12 years . However, limitations in
the studies prevent conclusions about cause and effect. Few children began vaccination at 9 –10
years , and there may have been differences in families or providers vaccinating at ages 9 –10
years . Additionally, multi -component interventions make it difficult to isolate the impact of
initiation  at ages 9 –10 years .
For the harms, Dr. Stefanos shared that some have raised concerns that changing the wording
may negatively affect the adolescent vaccination platform. While there are no data on what the
potential harm  might be , it is known that the HPV vaccine is often given alongside other
vaccines.  Among adolescents who  had received the HPV vaccine, 69.5% received it at the
same visit with at least one other vaccine.  An additional  concern is that changing the wording
could lead to system prompts at age 9  years , and vacci nation at that age may not be acceptable
to some providers.
A majority of work  group members felt that the anticipated desirable effects were moderate,
while the undesirable effects were considered minimal or small. A majority of work  group
members felt that the desirable effects outweigh the undesirable effects and favor  a change in
wording.
For the acceptability and values domain s, Dr. Stefanos shared that one study interviewed
providers and nurses involved in an intervention including vaccination at age 9, and they
generally had a positive experience. A small qualitative study in a rural setting found mixed
opinions. Three clinici an surveys were also conducted, with one showing that 61% of providers
not currently recommending vaccination at age 9 were willing to do so. The surveys found that
provider r ecommendations varied by provider special ty, patient age group, and framing of the
recommendation . Only two studies in the systematic review examined parents' perceptions of
vaccination at ages 9 –10 years . While few parents reported receiving recommendations to
vaccinate before age 11  years , most were willing  to do so.
Dr. Stefanos summarized that the AAP recommends starting the HPV vaccination  series
between the  ages of 9 and 12 years , and some stakeholders and advocacy groups support
starting at age 9. Changing the wording would clarify that vaccination at age 9 aligns with ACIP
recommendations. However, other stakeholders are concerned that this change could weaken
the adolescent vaccination platform. In a limited number of studies, vaccination at ages 9–10
was acceptable to providers and parents.
Work  group members felt that changing the wording of the routine vaccination age to 9 –12
years  was acceptable to stakeholders, with most responding "probably yes" or "yes." For parent
values, limited data were available for review, and a plurality of work  group members responded
"don't know" to the question about whether parents feel that desirable effects of changing the
39
 wording are large relative to the undesirable effects . Regarding uncertainty or variability in how
much parents value  changing the wording of the recommendation , a plurality indicated it was
"probably not important," while a minority felt it was "probably important."
The remaining domains in the EtR framework  and the summary work group interpretation  will be
presented  at a future ACIP meeting.
Dr. Loehr commented that he has not found the adolescent platform to be useful, noting that in
New York State, sixth graders require Tdap, and seventh graders need MenACWY, while HPV
is often mixed in. He observed that most parents do not want multiple vac cines given at once.
He expressed openness to hearing a defense of the adolescent platform to better understand
the rationale behind recommending it.
Dr. Asturias shared that strong evidence supports the efficiency of a 1 -dose approach, which
would nearly halve program costs and reduce the number of doses needed to provide the same
level of protection. He agreed with Dr. Loehr in discouraging the term " platform," emphasizing
that the role of ACIP members is to base recommendations on evidence, prioritizing
effectiveness, fewer doses, and safety.
Ms. Moser noted that data show the HPV vaccine is often given with other vaccines, even if not
in every practice. She expressed concern that the undesirable effects may be underappreciated,
pointing out that provider surveys indicate many parents are not r eady to discuss vaccination at
age 9. She also emphasized that the data on parental support for earlier vaccination were
limited. Additionally, she suggested that some potential benefits, such as improving how the
vaccine fits into the schedule,  could be a ddressed without this change and  CDSi tools could be
enhanced to allow more flexibility for institutions that prefer to recommend HPV vaccine
beginning at age 9 years . She questioned whether some of the stated benefits were as clear -cut
as presented.
Ms. Lyons commented that the adolescent platform will likely be reviewed in connection with
meningococcal vaccines, suggesting that changes to the platform may be forthcoming
regardless. It was noted that this potential review should be considered and may re duce
concerns about harm from altering the HPV vaccination schedule.
Dr. Lauri Markowitz (CDC/NCIRD) shared the work  group’s next steps and considerations. The
two policy questions under review are the wording of the recommendation for routine
vaccination age and the number of doses in the recommended HPV vaccination series.
In October, the topic was introduced to ACIP along with a review of data on vaccination at ages
9 to 10. The work  group found no strong evidence that starting at age 9 years improves
coverage compared to starting at 11 to 12  years . The plan is to clarify the recommendation by
changing the routine vaccination age wording to 9 through 12  years , making it clear that age 9
years is included. Dr. Stefanos presented part of the modified E tR today ; because this is a
minor wording change rather than a change to the  recommended age , GRADE is not being
used . The remainer  of the E tR will be presented in June.
In October, the work  group also introduced the topic of the number of doses in the HPV
vaccination series and reviewed key studies supporting reduction  in the number of doses , along
with global updates on one -dose recommendations. Today’s presentations included updated
data from major studies, a randomized trial (KEN SHE), U .S. coverage, and modeling. The work
group will continue focusing on this policy question through June. At the June meeting, data
from the ESCUDDO  trial comparing one versus two doses wi ll be presented, along with any
additional data requested by ACIP, a full E tR framework with GRADE, and, if ready, votes on
both policy questions.
40
 Dr. Markowitz explained that  ESCUDDO , the randomized trial in Costa Rica sponsored by the
U.S. National Cancer Institute, is evaluating whether one dose of the bivalent or 9-valent HPV
vaccine is noninferior to two doses in preventing HPV 16/18 infections in girls aged 12 to 16
years . It will also compare vaccinated participants with unvaccinated women using survey data.
Results are expected before the June meeting and will be presented to ACIP.
Outstanding questions remain regarding the number of doses, especially in three key areas.
First, on the duration of efficacy and immunogenicity of one dose, current data show protection
through 15 to 16 years with no evidence of waning, and more data are expected. Second, there
are no data on the protection at sites other  than the cervix. Third, for males, 13 of the 16 studies
reviewed included only females, and one -dose efficacy in males is not yet available. Some
studies have found that antibody levels a fter one HPV vaccine dose are lower in adolescent
males than in females; however, the clinical relevance is unclear.
In March 2024, Merck announce d plans for  clinical trials for 1-dose HPV vaccination.  Two
international, randomized , double -blind, efficacy clinical trials are planned , one in males 1 6-26
years of age, and one in females 16 -26 years of age.   The planned trials include elements
regulators have deemed necessary , including endpoints other than persistent cervical infection
and a comparison of 1 -dose and 3 -dose efficacy.  Merck has been in discussions with FDA and
EMA regarding trial design;  regulatory feedback  is an ticipated in Q2 2025.
It would be considered off -label if ACIP recommends one dose at any age or a two -dose
schedule for individuals aged 15 or older . Off-label use refers to anything not included in, or
differing from, the FDA package insert. Manufacturers can only promote and provide education
on FDA -licensed indications . It is important to note that ACIP has made many off -label
recommendations in the past, and at least 46 licensed vaccines in the U.S. have  some  off-label
recommendations, most of which apply to specific situat ions or subgroups.
The HPV Vaccines Work  Group is considering potential modifications to current
recommendations as data are reviewed. One option is expanding the 2 -dose recommendation
from ages 9 through 14 years to ages 9 through 26 years or through an older  age. Another
option under discussion is recommending 1 dose for certain age groups, such as 9 through 14
years , 9 through 20  years , or through an older age.
Dr. Markowitz concluded that all work  group members support modifying the HPV vaccination
schedule . However,  there are differing views on expanding the 2 -dose schedule or
recommending  1 dose for certain age groups. The work  group continues  to review data and
discuss the appropriate upper age range for these potential changes.   She closed with
questions for the committee on any questions or comments regarding the policy questions to be
addressed, and what additional information ACIP would like to see be fore potentially voting at
the next meeting.
Dr. Middleman commen ted on  the importance of vaccination platforms for adolescents, drawing
a parallel to the well -established platforms for infants and young children, which are deeply
integrated into anticipatory guidance and comprehensive care. It was noted that adolescent
platforms serve a similar purpose and contribute to consistent healthcare delivery. Data from the
2007 NCQA State of Health Care Quality report showed that adolescent immunization rates
among commercial payers rose from 10.5% in 1998 to 57.7% by 2006, following  the introduction
of new adolescent vaccines and the VFC program. This suggests that the formation of the
adolescent platform significantly improved vaccination rates. Additionally, upcoming data from
Dr. Zimet  is expected to show that many parents value the structure and expectations provided
by vaccination platforms. Using existing data  was encouraged  when evaluating the role of
platforms in adolescent immunization.
41
 Ms. Arthur noted that the company is pursuing an FDA indication for a 1 -dose HPV vaccine,
similar to the previous change from a 3 -dose to a 2 -dose schedule. She emphasized the
importance of alignment between agencies like the FDA and the CDC/ACIP process. She also
highlighted that the company would address  key data gaps discussed during the meeting,
including the efficacy of 1 dose in males. Ms. Arthur stressed the importance of maintaining
consistency and high evidentiary standards and encouraged considera tion of all available
evidence in the decision -making process.
Ms. Lyons encouraged the work  group to review the small number of states requiring  the HPV
vaccine to ensure that moving to a 1 -dose schedule or making other changes does not impact
existing school entry requirements.
Dr. Loehr responded that he is comfortable with the idea that earlier dosing provides better
protection, referencing a slide from the first presentation. He acknowledged that a 1 -dose
schedule has a lower seropositivity rate but noted uncertainty about the  clinical relevance of that
difference. He referenced Dr. Kim’s point that indirect  effects may be more impactful than
seropositivity. Dr. Loehr stated he would be more comfortable supporting fewer doses if there
were evidence that lower seropositivity is not clinically significant . He expressed interest in
seeing more data on that issue.
Dr. Markowitz clarified that Dr. Kim was referring to vaccine efficacy, noting that strong herd
protection could offset a small decline in individual efficacy. She explained that while antibody
titers are lower with one dose compared to two or three, no established minimum antibody level
is required for protection. Therefore, the clinical relevance of lower titers is uncertain. Dr.
Markowitz emphasized that efficacy data from studies such as KEN SHE, the Costa Rica
vaccine trial, and the IARC India study sh ow high protection with one, two, or three doses .
Dr. O'Leary noted that the American Academy of Pediatrics recommends HPV vaccination at
ages 9–12 years . He expressed that he has not seen compelling evidence supporting the
concept of the adolescent platform. He acknowledged that observational data suggest  that
allowing vaccination at ages 9 –10 may be beneficial. Ultimately, he emphasized that this may
be the only case where the wording of an ACIP recommendation itself serves as a barrier to
vaccination, by not clearly emphasizing the flexibility to begin at age 9.
Dr. Middleman expressed that the primary concern of the Society for Adolescent Health and
Medicine is to follow the evidence. While a change in recommendation would make sense if the
evidence strongly supported it, there is concern that current evidence ma y not be sufficient and
that potential harms are also hard to conclusively identify . The goal is to increase HPV
vaccination without unintentionally weakening the broader adolescent vaccination platform. It
was emphasized that any changes should be grounde d in evidence and that the current wording
does not appear to discourage vaccination.
Ms. Moser emphasized that this is a communication issue, not a change in recommendation.
Since HPV vaccination is already allowed at age 9  years , she cautioned that changing the
wording could raise concerns among parents and providers, especially given sensitivities
around the vaccine. The impact of the wording change on overall uptake should be carefully
considered.

CYTOMEGALOVIRUS (CMV ) VACCINES

Dr. Denise Jamieson (ACIP, Work  Group Chair) introduced the launch of the Cytomegalovirus
(CMV) Vaccines Work Group. The work  group will review CMV and congenital CMV (cCMV)
42
 epidemiology  and disease burden, CMV vaccine safety and immunogenicity data, and initial
work group considerations for CMV vaccine policy.

Dr. Tatiana Lanzieri (CDC/NCIRD ) reviewed the epidemiology and disease burden of CMV and
cCMV. cCMV is the most common infectious cause of congenital birth defects  in the U .S.,
affecting over 16,000 newborns annually  and is the leading non -genetic cause of childhood
hearing loss . It causes  an estimated 80 neonatal deaths and nearly 3,000 cases of cCMV
disease each year, with long -term outcomes including hearing loss, cognitive, or motor
impairments.

Congenital CMV may present at birth with signs  like rash, enlarged liver or spleen, or a small
head. Diagnosis is typically by PCR or culture of urine, blood, or cerebrospinal fluid within 21
days of life. Most newborns with cCMV infection have no clinical signs at birth  and go
undiagnosed. To improve detection, some U .S. states have implemented targeted or universal
screening  for cCMV .

In the U .S., two states have implemented universal newborn screening for cCMV, while 11
conduct targeted hearing screening. Three of those states also perform symptom -based
screening. Additionally, 13 states are conducting cCMV surveillance.  Data from all states are
unavailable;  cCMV prevalence likely varies by state due to differences in maternal age,
demographics, and population -specific CMV rates.  Data from CDC’s National Health and
Nutrition Examination Survey (NHANES) has shown that CMV IgG seroprevale nce increases
with age. From the 1988 -1994 NHANES cycle to the 1999 -2004 cycle , age-specific rates among
those aged 6 –49 years remained stable. However, from 2011 -2012  to 2017 -2020,
seroprevalence among  children aged 1 –5 years rose from 21% to 29%. Updated testing for
ages 6 –59 years from the 2017 –2020 NHANES cycle is ongoing.

CMV seroprevalence is higher among non -Hispanic Black and Hispanic women compared to
non-Hispanic White women. Among women aged 20 –29, rates are 36% for non -Hispanic White
and 77 –81% for non -Hispanic Black and Hispanic women.

Seronegative women are at risk for primary CMV infection during pregnancy, while seropositive
women may experience reinfection. The risk of vertical transmission is highest with primary
infection and increases by trimester, but severe outcomes like hearing  loss are more likely with
first-trimester infections. Non -primary infections have lower vertical transmission rates but can
still cause cCMV disease if transmission occurs early  in pregnancy . These findings suggest that
a CMV vaccine should be given befor e pregnancy to protect against vertical transmission
following primary infection .

The incidence of CMV primary infection and reinfection varies across populations. Proportions
of cCMV infections due to non -primary maternal infection (NPI) vary with maternal
seroprevalence . Still, the  risk of cCMV infection is higher when the mother is CMV seronegative
before pregnancy. About 12,000 (75%) cCMV infections in the U.S. every year may be
attributable to primary maternal infections.

Young children play a key role in CMV transmission, shedding high virus levels  in saliva and
urine for months after infection. Shedding peaks at 1 to 2 years of age, which is also when many
first-time mothers in the U .S. have a second pregnancy.

Modeling suggests that a vaccine given to infants, even if the duration of protection was short ,
could impact transmission to pregnant mothers and decrease cCMV infections. Models predict a
43
 varying  impact depending on the population to be vaccinated, vaccine efficacy, duration of
protection , and coverage .

Dr. Lanzieri summarized that CMV and cCMV epidemiology are complex and have many
unknowns. In the U .S., most cCMV cases are linked to primary maternal infection, while
globally, non -primary infections are more common. A CMV vaccine could reduce disease
burden by providing long -lasting protection before and during pregnancy or indirectly protecting
pregnant  women if given to toddlers.

Dr. Robert Paris (Moderna) presented an overview of the investigational CMV vaccine, mRNA -
1647. Globally, cCMV affects 1 in 70 to 1 in 208 births. It occurs in about 1 in 200 births in the
US, with annual healthcare costs of $6 to $7 billion. Approximate ly 1 in 5 infants with cCMV
(symptomatic or asymptomatic at birth) develop long -term disability. Limited options for
prevention, screening, and treatment make cCMV a major unmet medical need and a high
priority for vaccine development, as recognized by the WH O and the U.S. National Academy  of
Medicine.
The clinical program aims to prevent CMV infection in seronegative women by vaccinating
women of childbearing age before pregnancy, when the risk of transmission and complications
is highest. Due to the low incidence of cCMV and long -term outcomes, a large , lengthy Phase 3
trial would be impractical. Instead, the initial indication will target CMV prevention in females
aged 16 to 40  years of age , regardless of CMV serostatus.
Moderna’s investigational CMV vaccine (mRNA -1647) contains six mRNAs designed to elicit
both humoral and cellular immunity. Antigens were selected to prevent CMV infection and fetal
transmission.  Five mRNAs encode the pent amer subunits, required for CMV entry into most cell
types ; the other mRNA encodes glycoprotein B  which mediates fusion of virus and host
membranes during cell entry , which is necessary for viral infectivity.   Prior gB -based vaccines
showed 43 –50% efficacy ; adding  the pentamer glycoprotein  in mRNA -1647 is expected to
improve efficacy.
The Phase 1 trial was a randomized, placebo -controlled study of mRNA -1647 in healthy adults
aged 18 to 4 9 years of age , assessing doses from 30 to 300 micrograms. Among 154
participants, over half were CMV negative, and the vaccine was well tolerated with no safety
concerns. CMV -negative and -positive participants showed neutralizing antibodies, binding
antibodies, and cell -mediated responses. These results supported continued development and
informed dose selection within a narrower range.
In the Phase 2 study, 315 adults aged 18 to 40 were randomized 3 :1 to receive mRNA -1647 or
placebo on a 0 -, 2-, and 6 -month schedule. About 70% were CMV negative and followed for
approximately 12 months post -vaccination. Dose levels of 50, 100, and 150 micrograms were
evaluated in Part 1, while Part 2 focused on additional safety and immunogenicity data for the
100 microgram dose  which was the dose selected for the Phase 3 efficacy trial . The primary
objectives were safety and neutralizing antibody response s.
Solicited local reactions were self -reported by participants within 7 days for each injection. Pain
was the most frequent local reaction , reported by about 80% of participants ; local reactions
were mostly grade 1 or 2 and generally 1 -3 days in duration.   For systemic rea ctogenicity,
headache, fatigue, myalgia, and chills were most common.  There was some increase in
systemic reactions with second  and third doses .  Systemic reactions were generally grade 1 or
2 and of 1-2 days duration.   Related medically -attended adverse events  (primarily local injection
site reactions) occurred more frequently in vaccine recipients than placebo recipients.  No
significant safety concerns were identified during the study.
44
 Neutralizing antibody res ponse  to mRNA -1647 was based on bo th epithelial cell  and fibroblast
cell assays  to assess responses to both the pentamer and the gB  antigen.  Among CMV
seronegative participants , as assessed by epithelial cell infection, GMTs increased after each
dose and remained above the GMT seen in natural infection through 18 months ; as assessed
by fibroblast infection, GMTs reached the natural infection GMT at months 3 and 7, and then
declined at months 12 and 18.   Among seropositive participants,  after the first dose  antibodies
against epithelial cell infection increased approximately 17 -fold over baseline , and antibodies
against fibroblast infection increased about 2.4 -fold over baseline ; the second and third doses
did not appear to substantially increase antibody titers .  GMT s for both assays remained above
the natural infection GMT through month 18.
Demonstrating durable immune responses is key for vaccine implementation. Long -term follow -
up is underway in Phase 2 and 3 trials to assess immunogenicity and efficacy. Phase 2
participants were offered enrollment in an extension study with three additiona l years of follow -
up. An interim analysis was recently conducted on data up to 36 months post -vaccination.
Durable immune response was observed through three years after the first vaccination  among
seronegative participants , with GMTs remaining stable fro m 18 to 36 months  for both assays ;
Dr. Paris stated that results were similar for the seropositive cohort.
Dr. Paris summarized that mRNA -1647 was generally well tolerated with no safety concerns
identified . The 3-dose 100 microgram regimen was highly immunogenic . Neutralizing antibody
GMTs against epithelial infection remained above natural infection GMT through 12 months
after the last vaccination in SMV -seronegative participants ; a boost ing effect was observed in
CMV -seronegative participants. The vaccine induced durable epithelial and fibroblast
neutralizing antibody responses lasting up to three years.
The Phase 3 pivotal efficacy trial is a randomized, observer -blind, placebo -controlled study
enrolling females aged 16 to 40  years of age . CMV -positive participants help assess safety and
immunogenicity, while CMV -negative participants aged 20 and older had to have regular contact
with a child under five  years of age . Pregnancy was an exclusion criterion. Participants were
randomized 1:1 to receive 100 micrograms of mRNA -1647 or placebo on a 0 -, 2-, and 6 -month
schedule, with two years of follow -up after th e third dose to assess efficacy.
The trial's primary objective  is to evaluate vaccine efficacy against primary CMV infection in the
seronegative cohort, measured by seroconversion to CMV IgG positivity. Participants undergo
serology testing every three months starting 28 days after the last dose. Immunogenicity is a
key secondary objective, using endpoints and assays consistent with prior studies. CMV
shedding is also being assessed through PCR detection of CMV DNA in urine samples after
seroconversion and in CMV -positive participants thro ughout the study.
The study is being conducted in 290 sites in 13 countries.  Enrollment was completed in
October 2023, with 7,484 participants enrolled ; 80% were CMV -seronegative  and 20% were
CMV -seropositive.  The mRNA -1647 Phase 3 efficacy trial includes two planned analyses. An
independent Data Safety Monitoring Board (DSMB) conducted an interim efficacy analysis in
December 2024. The DSMB found no safety concerns and recommended that the study
continue as planned in a blinded manner. The final efficacy analysis is antic ipated in late 2025.
Dr. Paris concluded that mRNA -1647 has been generally well tolerated in adults aged 18 to 40,
regardless of CMV serostatus, in Phase 1 and 2 trials. The DSMB identified no safety concerns
during its review of unblinded Phase 3 data. In seronegative participants, the vaccine elicited
antibody responses that exceeded those seen in natural infection, with immune persistence
observed through three years. In seropositive participants, vaccinati on boosted immune
responses above baseline after the first dose. The Phase 3 efficacy trial is ongoing in
45
 seronegative and seropositive females aged 16 to 40  years , with the final efficacy analysis
expected by the end of th is year.
Dr. Shaw asked about  previous studies using subunit vaccines, specifically those containing the
pentamer complex and glycoprotein B ectodomain in nonhuman primate model, that found that
high neutralizing antibody levels did not prevent substantial horizontal transmission. He inquired
if the expectation is that the mRNA platform or use in humans will produce better outcomes. He
also asked which specific antibody responses are believed to b e necessary to prevent vertical
transmission to the infant.
Dr. Paris responded that there is still limited understanding of the specific or dominant antibody
response required to prevent vertical transmission. Regarding the nonhuman primate study, he
acknowledged familiarity with it, stating it was likely conducte d by Pfizer and involved a
recombinant pentamer vaccine with glycoprotein B. He noted limitations in the study design,
particularly related to the transmission model.
Dr. Wu (Moderna) noted that the study used rhesus CMV (RhCMV), which, while part of the
same beta herpesvirus family, may have a different pathogenesis than human CMV. A key
challenge in the CMV research community is the inability to use human CMV to infect animal
models. As a result, studies must rely on species -specific CMV, which limits how well animal
data can be translated to humans.
Dr. Zucker asked whether there is a known correlate of protection for CMV, noting that , based
on the discussion, there may not be one currently identified. She also asked about expectations
for individuals who are already seropositive, questioning whether vaccination is expected to
prevent reinfection or if those individuals would remain at risk upon re -exposure.
Dr. Paris responded that there is no known correlate of protection for CMV. Seropositive
individuals were deliberately included in the clinical development program because they still
face a significant risk of vertical transmission due to reinfection or re activation, with most cases
now believed to result from reinfection. Demonstrating impact on reinfection is challenging, as
current research tools are limited and unsuited  for Phase 3 trials. Post -licensure, the plan will
expand the clinical program to ass ess real -world effectiveness, including the impact on
congenital infection in both CMV -negative and CMV -positive populations. While the biological
significance is not fully understood, a reduction in viral shedding could indicate the vaccine’s
potential to  limit viral replication and reduce transmission in seropositive individuals during
pregnancy.
Dr. Zucker followed up by noting that approximately 1,800 participants in the study were
seropositive and asked about the expected incidence of CMV shedding over the course of the
study.
Dr. Paris responded that the point prevalence of CMV shedding in seropositive individuals likely
ranges from 5% to 20%, depending on how recently they were infected. He noted that the study
monitors this continuously and collects  specimens frequently enough to expect detection of a
significant frequency of viral shedding in this population.
Dr. Asturias inquired whether the antibodies have been tested for their ability to neutralize
various strains of CMV and how many strains they can neutralize. He also acknowledged that
cellular immunity data from the Phase 2 trial won’t be presented , but wondered if there were any
insights on cellular immunity development from the Phase 1 study.
Dr. Paris referenced a paper published in the Journal of Virology  that assessed wild -type clinical
strains of CMV using Phase 1 trial data. The study found no significant impact on neutralization
across different viral strains. Regarding T -cell immunity, Dr. Paris confirmed that Phase 1 data
46
 showed the induction of T-cell immunity  using an ELISPOT  assay. The team is now evaluating
these data with a more recent ex vivo intracellular cytokine assay  which  they hope to present
data at an upcoming meeting, showing evidence of T -cell responses immediately after
vaccination and up to 12 months later. He also noted that, similar to other mRNA -based
vaccines, they expect robust T -cell immunity.
Dr. Tatiana Lanzieri (CDC/NCIRD)  followed up with the work  group’s initial considerations for
CMV vaccine policy. The burden of congenital CMV is substantial, yet awareness is low.
Vaccine acceptability among the public and providers, as well as the feasibility of
implementation, needs assessment. Primary maternal infections, which vary by population
susceptibility, cause most cCMV infections in the U.S. and lead to more severe disease in the
first trimester. Vaccination before pregnancy and long -lasting protection throughout childbearing
years are necessary. CMV seroprevalence increases with age, but certain populations have
high prevalence by adolescence .
The Moderna CMV mRNA vaccine candidate encodes the CMV gB and pentamer complex with
a three -dose schedule over six months. The ongoing Phase 3 trial includes 7,500 non -pregnant
females aged 16 to 40  years of age , with about 5,000 CMV seronegative at enrollment. The
seronegative group will be evaluated for the primary endpoint of vaccine efficacy, while safety
and reactogenicity will be assessed in all participants. Participants will be followed for 24
months afte r the third dose, with a subset followed for 48 months.
The work  group reviewed data from Moderna's mRNA -1647 Phase 1 and Phase 2 trials, with
initial findings indicating no safety concerns and promising immunogenicity. There is a need to
better understand  differences in neutralizing antibody levels against epithelial cell and fibroblast
entry  and the cell -mediated immune response, including antibody -dependent cellular cytotoxicity
and phagocytosis. Regarding long -term protection, the Phase 2 extension data show antibody
persistence for at least three years afte r the first dose . Still, it  remains important to determine if
protection lasts throughout childbearing years.
Moderna’s planned vaccine indication is for non -pregnant females aged 16 –40 years , with a 3 -
dose series over 6 months. Efficacy will be assessed for primary infection in initially CMV -
seronegative subjects. Data on immunity duration will be limited ; protection is needed before
pregnancy and throughout childbearing years. Efficacy against vertical transmission and cCMV
infection or disease is yet to be determined. A better understanding of the correlates of
protection against vertical transmission is needed.  The benefit for CMV -seropositive individuals
remains unclear, and serological testing prior to vaccination presents implementation
challenges. Vaccine recommendations may evolve as future clinical trial data becomes
available for other groups, such as ado lescents and transplant patients.  Over the next several
months, the CMV work  group will continue to review data as it becomes available and address
additional domains within the E tR framework.
Dr. Lanzieri concluded by emphasizing that an effective CMV vaccine could reduce disease
burden, with over 16,000 children born with cCMV infection in the U.S. each year, nearly 3,000
with cCMV disease. The mRNA -1647 CMV vaccine has shown safety and immunogenic in
Phase 1 and 2 trials, with efficacy data from the ongoing Phase 3 trial expected next year. The
vaccine should be given before pregnancy to prevent infection and reduce vertical transmission,
especially in the first trimester. Protection against non -primary infections is also i mportant.
Challenges may include low awareness of cCMV and the need for serological screening before
vaccination. The CMV ACIP work  group will regularly  review data and develop vaccine policy
options.
Dr. Shaw inquired about potential plans to test the vaccine in transplantation settings, where
reactivated CMV disease remains a significant issue. He noted that CMV reactivation in aging
47
 immune systems can skew the CD8 cell repertoire and asked if there are any ongoing studies or
plans related to this context.
Dr. Paris confirmed that testing the vaccine in transplant settings is an active part of their
program. Moderna is currently  conducting a study on  hematopoietic stem cell transplant
recipients, with ongoing enrollment. He acknowledged the significant unmet medical need in
both stem cell and solid organ transplant populations due to CMV. Regarding the impact of
CMV on aging and immune response, Dr. P aris noted ongoing discussions and welcomed input
from the work  group on how to address this issue as it relat es to an aging population.

U.S. MEASLES UPDATE

Dr. Talbot began her introduction of the session with a statement that she finds it devastating
that this update was needed; the measles vaccine is very effective  with a long duration of
protection , and children in the U.S. should not be dying of measles.

CAPT  David Sugerman (CDC/NCIRD) shared an update on measles. Before the measles
vaccine, there were 3 to 4 million cases annually in the US, with 500,000 reported. Cases
dropped significantly after the vaccine was introduced in 1963. In 1989, the ACIP recommended
a second dose at school entry due to school outbreaks. By 2000, the U.S. achieved measles
elimination, defined as the absence of continuous spread of the disease for 12 months.

Since measles elimination, there have been 11 large outbreaks in the U.S. with more than 50
cases. Seven outbreaks occurred in the last 5 years, and nine were among close -knit
communities with low vaccine coverage. Coverage in these communities was far below the 95%
threshold needed for herd immunity. The most recent outbreak, c oncentrated in Gaines County,
Texas, involved a 2 -dose MMR coverage rate of 82% in public schools, with true coverage likely
lower due to homeschooling or private schools without rep orted coverage. The outbreak spread
to 21 additional counties in Texas and three counties in eastern New Mexico.

From elimination until the COVID -19 pandemic, MMR coverage remained above the 95%
threshold needed for herd immunity. However, coverage has decreased since the pandemic.
During the 2023 –2024 school year, approximately 280,000 (7%) kindergarteners lacked
documentation of two MMR doses, potentially putting them at risk for measles. MMR coverage
also varies across states, with several reporting coverage below 90%. Coverage is also quite
heterogeneous at the county level , potentially hiding true outbreak risk.

Following the COVID -19 pandemic, measles has resurged due to increased transmission
abroad, a surge in international travel, and declines in vaccination, especially in close -knit
communities with already low coverage.  Cases rose from 59 in 2023 to 285 in 2024, and by
April 10, 2025, had more than doubled to 712.

From 2023 to 2025, the number of outbreaks fluctuated between 4 and 16  per year , while the
proportion of total cases linked to outbreaks increased from half to 93% this year, with five
outbreaks ongoing. Efforts will focus on tracking the duration of these outbreaks and working
closely with state and local partners to ensure the 12 -month threshold is not exceeded,
preserving elimination status, especially wit h ongoing spring and summer travel and congregate
events.

48
 As of April 10, 2025, 712 cases have been reported by 25 states  in 2025 ; most states are
reporting no or limited spread from importations . Over 90% of current national cases are linked
to the southwest outbreak, driven by transmission in close -knit, under -vaccinated communities
with low vaccine coverage. There  are currently  large outbreaks in the same close -knit
community as the southwest outbreak in Ontario, Canada, and Chihuahua, Mexico.

There are two circulating measles genotypes in the US: B3 and D8, with D8 being the
predominant genotype. Four distinct sequence identifiers (DSIDs) have been identified for B3
and six for D8 this year. In this outbreak, most sequences are D8 DSID 9171, fo und in Texas,
Oklahoma, New Mexico, Kansas, and  Chihuahua, Mexico, and Ontario, Canada, within the
same under -vaccinated community. Four other D8 DSIDs, differing by one to two nucleotides,
are also linked to the Texas outbreak. Most B3 sequences are from Vietnam, which is
experiencing a large outbreak.

CDC ’s 2025 measles outbreak response efforts include  a variety of initiatives across different
areas. From March 4 through April 1 , 15 CDC deployers provided on -site technical assistance in
Texas, with additional teams deploying this week. Remote technical assistance was provided to
state health departments. Biweekly national measles calls with public health partners  and
trilateral calls with Canada and Mexico  were held to share updates and lessons learned.
Additional MMR vaccine doses were made available to health departments. Provider outreach
included releasing a Health Alert Network (HAN) advisory on the expanding measles outbreak
in Texas and New Mexico and  guidance for the upcoming travel season. Clinician Outreach and
Communication Activity (COCA) and Epi -X alerts were issued, and a provider letter was shared
summarizing routine and outbreak -related MMR vaccination recommendations. Laboratory
support effor ts included coordination with the Association of Public Health Laboratories Vaccine -
Preventable Disease Reference Centers for genotyping and sequencin g; expanded testing for
wastewater surveillance with the National Wastewater Surveillance System and the Center of
Excellence in Texas ; and ongoing modeling to assess risk.

Dr. Asturias noted that in the Texas outbreak, with two deaths of school -age children and 41
reported cases in Lubbock , there’s a case fatality rate of about 4.8%, much higher than the
typical measles case fatality rate of 1 –2 per thousand in outbreak situations. He questioned
whether this higher mortality might reflect the underreporting of measles cases in the
jurisdiction.

CAPT  Sugerman confirmed that there are likely many underreported measles cases. In
discussions with families in Texas, some have mentioned prior cases that recovered without
testing, while others had cases but never sought treatment. He highlighted under -testin g, under -
diagnosis, and under -reporting as contributing factors resulting in a smaller denominator. This is
particularly common in close -knit communities with lower healthcare -seeking behavior.

Dr. Zucker asked about resource mobilization during the Texas outbreak, drawing on
experience managing the largest measles outbreak in New York City since 1992. The response
required significant resources, with costs around $8.4 million and 7% of the healt h department
involved. Dr. Zucker inquired about the scale of the response in Texas and other areas with
ongoing outbreaks, specifically regarding resource mobilization to end transmission.

CAPT  Sugerman shared that Texas has requested significant resources. With COVID -19
funding diminishing, Texas is reallocating staff and resources from other domains and regions to
support the measles response. Additional financial and personnel support is neede d, estimated
at $30,000 to $50,000 per measles case for public health response. While efforts are being
49
 made to support Texas and other jurisdictions, securing sufficient resources and personnel
remains challenging .

Dr. Zucker emphasized that it's not just about money, but also the need for adequate staff. It
was noted that contact investigations, follow -up communications, and other tasks require
significant personnel, especially for an outbreak of this scale.

Ms. Moser asked when the U .S. could lose its measles elimination status, noting that elimination
is defined by the absence of continued spread for 12 months.

CAPT  Sugerman confirmed that the U .S. would lose its measles elimination status after 12
months of ongoing circulation of the same sequence. With four months in, this would occur
around January 20th of the following year.

Dr. Kevin Ault (ACOG) inquired about the number of stillbirths, miscarriages, and pre -term
deliveries during the current outbreak in Texas, noting the considerable morbidity among
pregnant women in the 2019 New York City outbreak.

CAPT  Sugerman confirmed that there have been no reports of stillbirths or miscarriages but
noted that measles cases in pregnant women, including one case of congenital measles, have
been tracked. He emphasized that pregnant women with measles face significant r isks,
including preterm labor, complicated deliveries, and negative infant outcomes. Additionally,
there have been exposures  in hospitals, where pregnant women may not initially show
symptoms or a rash, leading to exposure s of others.

As a family physician, Dr. Loehr mentioned seeing adults born between 1963 and 1968 who are
unsure whether they received the killed virus vaccine and need a booster or titer. He noted that
research indicates only a minority from those years received the killed virus vaccine. He asked
for suggestions for primary care doctors when facing this question from patients.

CAPT Sugerman confirmed that less than 5% of vaccines administered between 1963 and 1967
were the inactivated version, which had lower efficacy. He emphasized that most people are
likely protected . He stresses the importance of  primary care doctors having  direct
communication with patients. Some may request a titer, while others may prefer an additional
vaccine. Overall, the risk at the population level is very low due to the small number of
individuals who received the inactivated vaccine.

Dr. Talbot highlighted the importance of the work done by CDC colleagues and of available
vaccines, thanking everyone involved .

Dr. Wharton announced that a new webcast link for the following day’s meeting would be posted
later in the evening and reminded attendees that it would not be the same link used that day.
She thanked all ACIP members for their flexibility in attending the rescheduled meeting, as well
as the ex officio members, liaisons, and work  group leads for their excellent work. She also
expressed appreciation to the ACIP Secretariat for their preparation, CDC’s Office of
Communications and NCIRD’s communications team f or their excellent support, and the
engineers at the CDC’s Global Communications Center for helping the meeting run smoothly.
She noted that while many challenges had been anticipated, most were avoided thanks to the
collective efforts of everyone involved.

50
 With no additional business posed for the day, the ACIP meeting stood in recess until 8:00 AM
on April 16, 2025.

WEDNESDAY : APRIL 16, 2025

WELCOME AND INTRODUCTIONS

Call to Order/Roll Call

Dr. Keipp Talbot (ACIP Chair) called to order and presided over the April 16, 2025, Advisory
Committee on Immunization Practices (ACIP) meeting. She then conducted a roll call, which
established that a quorum was present. A list of members,  ex officio members , and liaison
representatives is included in the appendices at the end of this summary document. No COIs
were identified for the second day of this meeting. Dr. Chen noted that there was no conflict of
interest but stated a decision to abstain from voti ng on chikungunya vaccine items due to prior
involvement in data and safety monitoring board activities. Dr. Kuchel stated there were no
current conflicts of interest but would abstain from voting on the RSV recommendations due to
having served as a consul tant for approximately six months about a decade ago.

MENINGOCOCCAL VACCINES

Dr. Jamie Loehr (ACIP, Work Group  Chair) introduced the meningococcal vaccines session.
The Meningococcal Vaccines  Work Group has been developing recommendation options for
GSK’s pentavalent MenABCWY  vaccine, which was licensed on February 14, 2025.  A vot e on
this product and a VFC vote is scheduled for this meeting.  The work group is also discussing
Sanofi’s MenACWY (Men Quadfi®) for use in infants.  An extension of licensure  of this product  to
age 6 weeks is anticipated in May 2025,  to be followed by an ACIP vote in June 2025.
Additionally, t he work group continues to discuss possible changes to the meningococcal
vaccine schedule for adolescents.

In October 2024, the work  group presented an E tR for the GSK pentavalent vaccine and made
a recommendation to the ACIP. At that meeting, the work  group also recommended changing
the BEXSERO  schedule from 0 , 1 month to 0 , 6 months based on evidence that longer spacing
improved immunogenicity. As a result, some calculations and evaluations had to be redone. The
GSK pentavalent vaccine, when compared to BEXSERO  with updated data, showed
comparatively lower immunogenicity. Some analyses revealed that MenB alone  performed
better  than the  pentavalent vaccine , with non -overlapping confidence intervals. However, there
is no established clinical correlate of protection, and the clinical significance of these findings
remains uncertain. The work  group reviewed the changes and updated the E tR accordingly, but
the overall recommendation to ACIP did not change.

Dr. Sarah Schillie (CDC/NCIRD) reviewed the updated EtR and work  group considerations for
the GSK pentavalent MenABCWY vaccine .  Currently , ACIP recommends  one MenACWY dose
at age 11 –12 years and a booster dose at age 16 years. Two MenB doses are recommended at
age 16 –23 years  based on shared clinical decision -making , with a p referred age range  of 16–18
years.
For persons ≥2 months of age at increased risk, MenACWY vaccines are recommended for
specific medical conditions, some microbiologists, exposure  during an outbreak , travel to
51
 hyperendemic areas, and first -year college students. MenB vaccines are recommended for
persons ≥10 years of age with certain medical conditions, some microbiologists, and those with
exposure  during an outbreak .
MenACWY vaccine products are interchangeable; while using the same brand is preferred, it is
not required for all doses in a series. In contrast, MenB vaccine products are not
interchangeable. MenB vaccines from the same manufacturer must be used for all d oses in the
series, including booster doses.
Two MenABCWY vaccines are available in the U.S., one made by Pfizer (PENBRAYATM) and
the other by GSK (PENMENVY ). Both vaccines combine an existing MenACWY and MenB
vaccine. They are both licensed as a two -dose series, with doses separated by six months for
persons aged 10 –25 years. The Pfizer vaccine was licensed in October 2023, and the ACIP
voted on recommendations at its October 2023 meeting. The GSK vaccine was licensed on
February 14,  2025, and the ACIP will vote on recommendations for this vaccine today.
ACIP recommended that the Pfizer pentavalent vaccine may be used when both MenACWY
and MenB vaccines are indicated at the same visit for healthy persons aged 16 –23 years when
shared clinical decision -making favors MenB vaccination, and for persons aged ≥10 years who
are at increased risk for meningococcal disease.
Due to a lack of direct comparison data, the meningococcal vaccines work  group assessed the
Pfizer and GSK pentavalent vaccines separately. The MenACWY and MenB vaccine indications
have not changed with the availability of the pentavalent vaccines. ACIP previously expressed a
preference to harmonize recommendations for the Pfiz er and GSK pentavalent vaccines unless
a vaccine -specific reason for differences exists.
Immunogenicity of meningococcal vaccines is measured using various assays. Traditional
human  serum bactericidal antibody  (hSBA ) assays use exogenous complement to assess
seroprotection, seroresponse, or GMTs. For MenB strains, endogenous complement can be
used to measure immune response against diverse serogroup B strains. However, a serologic
correlate of protection exists only for serogroup C.
GSK’s pentavalent vaccine was assessed using three policy  questions.
Policy question 1
Should the GSK pentavalent vaccine be included as an option for MenACWY/MenB vaccination
in people currently recommended to receive both vaccines at the same visit?
– For example, 16 year -olds who decide to receive MenB vaccine based on shared clinical
decision -making
Policy question  2
Should the GSK pentavalent vaccine be included as an option for people currently
recommended to receive MenACWY only?
–For example, 11 –12 year -olds
Policy question  3
Should the GSK pentavalent vaccine be included as an option for people currently
recommended to receive MenB only?
– For example, during a serogroup B outbreak
For ease of communication , the quadrivalent MenACWY vaccine is referred to as "Q," the MenB
vaccine as "B," and the pentavalent vaccine as "P."  Using this nomenclature,  the current ACIP
recommendation can be summarized as Q-QB-B (if MenB vaccine is included) or Q-Q (if it is
52
 not).  The work group supported  the use of GSK’s pentavalent vaccine as an option for
MenACWY/MenB vaccination in people currently recommended to receive both vaccines at the
same visit (Q-P-B), but not for those currently recommended to receive only MenACWY (P -P) or
Men B ( Q-P-P).
Dr. Schill ie then reviewed the updated EtR.  For public health problem, Dr. Schillie shared that
meningococcal disease incidence in the U.S. declined dramatical ly from 1996 to 2019, with
further decreases in 2020 and 2021. This decline began before vaccine introduction. Since
2022, however, cases have increased. Preliminary 2024 data show 503 cases, the highest
incidence since 2013, at 0.15 per 100,000 population . The work group felt that invasive
meningococcal disease is of public health importance for all  three policy question s for the GSK
pentavalent vaccine.
The work  group previously assessed the GSK pentavalent vaccine using BEXSERO
administered on a 0 -, 2-month schedule as the comparator for the MenB antigens. BEXSERO
was initially licensed as a two -dose series given at 0 and ≥1 month. The dosing schedule was
recently changed  to 0, 6 months, and because longer intervals improve immunogenicity, this
raises the bar  for comparison .
The clinical significance of the comparatively lower immunogenicity is uncertain, as no serologic
correlate of protection exists for serogroup B disease. The work  group’s recommendations for
use of the GSK pentavalent vaccine remain unchanged, but the work  group believes ACIP
should consider the changes in comparative immunogenicity during its deliberations.
The work  group’s previous synthesis presented to ACIP found the GSK pentavalent vaccine
noninferior  based on hSBA titers  to MenB on a 0, 2 month schedule  for three strains and on a 0,
6 month schedule  for two strains. Noninferiority was not demonstrated for the PorA indicator
strain at either the 0 –2 month or 0 –6 month comparison. This strain is important as it represents
the vaccine's full outer membrane vesicle component and may impact cross -protection.
Success criteria for MenB protection using an endogenous complement hSBA assay were met
against a broad range of strains, despite lower point estimates  compared to MenB on a 0, 6
month schedule. Findings regarding serogroups A, C, W, and Y immunogenicity and safety
remain unchanged. The pentavalent vaccine had a similar safety profile to Men B, with slightly
more unsolicited adverse events than MenB ; there were more adverse events with the
pentavalent vaccine than were seen with MenACWY.
Final  analyses of immunogenicity, as reflected in the package insert, were slightly different than
what had been previously shared with ACIP ; Dr. Schillie reviewed a number of these differences
for the committee.  Most differences were small  and t hey did not change the work group’s
overall interpretation.
The work group  previously determined that the desirable anticipated effects of the GSK
pentavalent vaccine were small for all three policy question s. This assessment remains
unchanged. The work group  previously determined the undesirable effects to be minimal for
policy question  1 and small or minimal for the other policy question s. This assessment remains
unchanged. For policy question  1, based on new immunogenicity data, a minority of the work
group  now favors “favors comparison.” The overall certainty of evidence for short -term immunity
was rated as moderate or low for the three policy question s. This determination remains
unchanged from the work group ’s previous assessment. The overall certainty of evidence for
serious adverse events was rated as moderate or low for the three policy question s. This
determination also remains unchanged from the work group ’s previous assessment.
For resource use, Dr. Schillie shared that the expected price of the GSK pentavalent vaccine
remains lower than the combined prices of the component vaccines. For policy question  1, the
53
 health outcomes are identical for the pentavalent vaccine and comparator, each preventing 91
cases of invasive meningococcal disease and 14 deaths compared to no vaccination.
Regarding incremental cost -effectiveness ratios, as previously shared, QPB is cos t-saving
compared to the current strategy of Q -QB-B, saving $175 million with no difference in quality -
adjusted life years. In the sensitivity analysis with updated price assumptions, QPB remained
cost-saving. The work group  concluded that policy question  1 would be an efficient allocation of
resources, but this varied for policy question s 2 and 3. The work group ’s assessment remains
unchanged.
The work group  continues to believe there is sufficient information to support a
recommendation. The work group  recommends the pentavalent vaccine for policy question  1,
does not recommend it for policy question  2, and is divided on policy question  3.
Recommending for policy question  1 aligns with the existing recommendation for the Pfizer
pentavalent vaccine.
Policy question  1 typically involves one dose of the pentavalent vaccine and one dose of MenB
to complete the MenB series. However, the studies evaluated two doses of the pentavalent
vaccine. Recommendations for both pentavalent vaccines may be revisited in future adoles cent
schedule discussions.
The proposed vote language is:
ACIP recommends GSK’s MenABCWY vaccine may be used when both MenACWY and MenB
are indicated at the same visit*
*1) healthy persons aged 16 –23 years (routine schedule) when shared clinical decision -making favors administration of MenB
vaccine and 2) persons aged ≥10 years who are at increased risk for meningococcal disease (e.g., because of persistent
complement def iciencies, complement inhibitor use, or functional or anatomic asplenia)
Dr. Talbot asked whether these products can be mixed and matched with the availability of the
new QPB, the existing version, and the potential for another in the future.
Dr. Schillie responded that the manufacturer's MenB vaccine products remain non -
interchangeable. Only Pfizer products can be used if a Pfizer product was used to initiate the
series, and the same applies to the GSK product.
Dr. Schec hter noted that he was under the impression there was more support for policy
question  3 regarding the GSK product compared to past deliberations for the Pfizer product. He
asked if that is the case and whether there is clarity on why that might be.
Dr. Schillie stated that there was more support for the GSK product under policy question  3
compared to policy question  2. However, the work group  ultimately favored policy question  1.
This position is primarily based on ACIP’s desire to harmonize recommendations between the
Pfizer and GSK pentavalent vaccines. She noted that policy question  3 would involve
administering additional ACWY antigens.
Dr. Schec hter asked whether, in the coming years, it is likely or unlikely that real -world
effectiveness data will become available, either from post -immunization infections or outbreak
settings.
Dr. Schillie responded that she was unsure, noting that the rarity of the disease makes it
challenging to calculate real -world effectiveness. While some effectiveness data exist, they are
limited by small sample sizes.
Dr. Barnett asked whether the work group considered a different recommendation for travelers
to the meningitis belt of sub -Saharan Africa, given the reduced response to serogroup A, which
is more common in that region.
54
 Dr. Schillie explained that MenABCWY vaccines are typically not indicated for travel, as MenB
alone is not recommended based on travel. Travel would not meet that criterion since the
pentavalent vaccine is intended for use when both MenB and MenACWY are in dicated.
However, she acknowledged that reduced immunogenicity to serogroup A may be more relevant
for travelers. Still, the pentavalent vaccine would generally not be expected for travel -related
use.
Dr. Brewer asked how many vaccine types a pediatrician would need to stock to meet the new
recommendations under policy question  1, which includes the Q, P, and B components. He
questioned whether it would require stocking five different vaccines.
Dr. Schillie clarified that the pentavalent vaccine is optional. Providers could continue stocking
one MenACWY product and one MenB product. If they wish to reduce the number of injections,
they could add the pentavalent product corresponding to the MenB m anufacturer they already
use.
Dr. Brewer asked whether providers should stock both MenB vaccines because the products
are not interchangeable.
Dr. Schillie responded that that would not be necessary, as providers could refer out the likely
relatively few patients in their practice needing the other brand.
Dr. Zucker stated that, from a programmatic perspective, she supports harmonizing the
schedule whenever possible, given its complexity. Unless there is a compelling reason to
differentiate recommendations, she favored using the pentavalent vaccine when bot h
components are indicated and not allowing for alternative options.
Dr. Asturias asked how the work group  reconciled maintaining shared clinical decision -making
with the potential cost savings of using a pentavalent vaccine. He noted that, given the
complexity of the recommendations, practices may limit which vaccines they stock. He
questioned whether limitin g a potentially cost -saving pentavalent vaccine to a small subset of
adolescents was appropriate or if he had misunderstood the approach.
Dr. Schillie explained that the pentavalent vaccine is priced significantly lower than the
combined cost of the two -component vaccines. However, since it includes the MenB
component, its use remains subject to shared clinical decision -making. She noted tha t this
approach may be revisited in the future as part of adolescent schedule discussions, but for now,
the MenB recommendation remains unchanged.
Dr. Shaw asked about the consideration of noninferiority for the PorA antigen, noting that PorA
exhibits substantial phase variation in expression and sequence variation within and across
strains. He wondered whether this is accurate and how much strain ma tching should be
expected for a highly polymorphic protein.
Dr. Schillie explained that the PorA strain is important because it represents the vaccine's full
outer membrane vesicle component. This strain did not show noninferiority in the exogenous
assay. However, she emphasized that the post hoc analysis shown in the presentation
suggested similar  coverage for pentavalent and BEXSERO  for PorA  in U.S. strains , while the
data shown for the exogenous assay  may better represent New Zealand strain s and be less
relevant to the U.S. context.
Dr. Kurilla, referencing the risk -based meningococcal vaccine recommendation slides, noted
that MenB is currently used on a limited, risk -based basis. He asked about a scenario in which a
college student who previously received a pentavalent vaccine experi ences an outbreak at their
college. He questioned whether a MenB vaccination would be recommended in that setting and
how likely it would be for the booster to match the original pentavalent br
…[truncated]

Summary: MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)   APRIL 15-16, 202 5  MEETING SUMMARY   Trade names are used for identification purposes only and do not indicate endorseme nt.  2 TUESDAY : APRIL 15, 2025  WELCOME AND INTRODUCTIONS  Call to Order/Roll Call   Dr. Keipp Talbot (ACIP Chair) called the April 15, 2025, Advisory Committee on Immunization  Practices (ACIP) meeting to order.  Dr. Melinda Wharton (ACIP Executive Secretary) made  opening announcements about the…