summary 2023 10 25 26 508

MEETING OF THE ADVISORY
COMMITTEE ON IMMUNIZATION
PRACTICES (ACIP)
OCTOBER 25 -26, 2023
MEETING SUMMARY
CONTENTS
WEDNESDAY: OCTOBER 25, 2023 .............................................................................. 4
Safety of Quadrivalent Recombinant Influenza Vaccine in Pregnant Women and Their
Safety of Simultaneous versus Sequential Administration of mRNA COVID -19 and
Quadrivalent Inactivated Influenza (IIV4) Vaccines: A Randomized Placebo Controlled Trial Safety of Simultaneous Vaccination with Zoster Vaccine Recombinant (RZV) and WELCOME AND INTRODUCTIONS ................................................................. 4
MENINGOCOCCAL VACCINES ...................................................................... 4
Introduction ............................................................................................................................ 4
Plan for Revisiting Adolescent Schedule for Meningococcal Vaccines ................................. 5
Comparison of Pfizer and CDC Cost -Effectiveness Analyses ............................................... 8
Pfizer Statement .................................................................................................................. 16
Summary of EtR and Proposed Recommendations for Pfizer’s MenABCWY Vaccine .......17
Vaccines for Children (VFC) Resolution .............................................................................. 30
Vote: Meningococcal Vaccine .............................................................................................. 31
Vote: Meningococcal VFC Resolution ................................................................................. 32
MPOX VACCINES ........................................................................................ 33
Introduction .......................................................................................................................... 33
Updates about US Mpox Epidemiology, Vaccine Safety, and Vaccine Effectiveness ......... 35
EtR Framework for the JYNNEOS Vaccine ......................................................................... 40
Review of Voting Language and Clinical Guidance ............................................................. 50
Vote: Mpox Vaccine Recommendation ................................................................................ 53
Vote: VFC Mpox Resolution ................................................................................................ 54
ADULT RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINES ....................... 55
Introduction ........................................................................................................................ 55
INFLUENZA VACCINES ............................................................................... 73
Introduction .......................................................................................................................... 73
Infants .................................................................................................................................. 74
............................................................................................................................................. 77
Quadrivalent Adjuvanted Inactivated Influenza Vaccine (allV4) .......................................... 81
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   Effectiveness of Maternal Influenza Vaccination during Pregnancy against Influenza-
Associated Hospitalizations & Emergency Department Visits in Infants <6 Months of Age 84
Update on Influenza B/Yamagata Surveillance ................................................................... 87
Post Marketing Study: Pregnancy Outcomes with ccIIV4 (Flucelvax) ................................. 90
UPDATE ON COVID -19 AND INFLUENZA VACCINE SAFETY ........................ 92
Introduction ........................................................................................................................ 92
PUBLIC COMMENTS ................................................................................... 98
Overview .............................................................................................................................. 98
Public Comments ................................................................................................................. 98
THURSDAY: OCTOBER 26, 2023 ............................................................................. 103
AGENCY UPDATES .................................................................................... 103
Centers for Disease Control and Prevention ..................................................................... 103
Centers for Medicare and Medicaid Services .................................................................... 105
Food and Drug Administration ........................................................................................... 106
Health Resources and Services Administration ................................................................. 106
Indian Health Services ....................................................................................................... 107
National Institutes of Health ............................................................................................... 107
Office of Infectious Disease and HIV/AIDS Policy ............................................................. 108
Sanofi Statement ............................................................................................................... 109
COMBINED IMMUNIZATION SCHEDULE ..................................................... 110
Introduction ........................................................................................................................ 110
2024 Child and Adolescent Schedule Revisions ............................................................... 111
2024 Adult Schedule Revisions ......................................................................................... 118
Vote: Immunization Schedules .......................................................................................... 123
CHIKUNGUNYA VACCINE .......................................................................... 123
Introduction ........................................................................................................................ 123
EtR and Proposed Policy Options for Chikungunya Vaccine Use Among US Adults Traveling Abroad ............................................................................................................... 124
EtR and Proposed Policy Options for Chikungunya Vaccine use Among Laboratory Workers ............................................................................................................................. 132
DENGUE VACCINE .................................................................................... 135
COVID -19 VACCINES ................................................................................. 137
Introduction ........................................................................................................................ 137
Implementation Update on 2023– 2024 COVID -19 Vaccines ............................................ 137
COVID -19 Vaccine Policy and Next Steps ........................................................................ 141
PNEUMOCOCCAL VACCINES ..................................................................... 146
PUBLIC COMMENTS .................................................................................. 149
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  Overview ............................................................................................................................ 149
Public Comments ............................................................................................................... 150
CERTIFICATION ......................................................................................................... 154
ACIP MEMBERSHIP ROSTER .................................................................................. 155
ACRONYMS USED IN THIS DOCUMENT ................................................................. 164
WRITTEN AGENCY UPDATES SUBMITTED ............................................................ 169
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 WEDNESDAY: OCTOBER 25,  2023
WELCOME AND INTRODUCTIONS
Dr. Grace Lee (ACIP Chair) called to order and presided over the October 25-26, 2023
Advisory Committee on Immunization Practices (ACIP) meeting. She co nducted a roll call each
day, which established that a quorum was present. A list of Members, Ex Officios , and Liaison
Representatives is included in the appendixes at the end of this summary document. No
conflict s of interest (COIs) were identified during this meeting and quorum was maintained
throughout both days.
Dr. Melinda Wharton (ACIP Executive Secretary, CDC) noted that copies of the slides for the
meeting were available on the ACIP website and were made available through a ShareLink ™
file for ACIP Voting, Ex Officios , and Liaisons Members. She provided housekeeping
instructions and explained that the ACIP is, at its heart, a public body. Engagement with the
public and transparency in all of its processes are vital to the committee’s work. She indicated that there would be 2 oral public comment sessions during this meeting, which were scheduled
for approximately 12:50 PM Eastern Time ( ET) on October 25, 2023 and at approximately 10:00
AM on October 26, 2023. To create a fair and more efficient process, individuals interested in
making an oral comment were asked to submit a request online in advance of the meeting.
Priority is given to advance requests. If more people make requests than can be accommodated in the allotted time, speakers are selected through a blind lottery. The 14 speakers selected by lottery for this meeting were notified in advance of the meeting. Members of the public also had
the opportunity to submit written comments on issues coming before the ACIP via
https://www.regulations.gov using Docket Number ID CDC-2023-0 079. More information on the
written public comment process can be found on the ACIP website.
As noted in the ACIP Policies and Procedures manual , ACIP members agree to forgo
participation in certain activities related to vaccines during their tenure on the committee. For
certain other interests that potentially enhance a member’s expertise while serving on the committee, CDC may issue limited COI waivers. Members who conduct vaccine clinical trials or
serve on data safety monitoring boards (DSMBs) may present to the committee on matters
related to those vaccines, but those members are prohibited from participating in committee
votes on issues related to those vaccines. Regarding other vaccines of the concerned company,
a member may participate in discussions with the provision that he/she abstains on all votes related to that company. ACIP members state any COIs at the beginning of each day of each
meeting.
MENINGOCOCCAL VACCINES
Introduction
Katherine Poehling, MD, MPH (ACIP, WG Chair) introduced the Meningococcal Vaccine Work
Group (WG). She reminded everyone of the 3 policy topics under consideration by the WG
(pertaining to the Pfizer pentavalent vaccine):
1. Should pentavalent vaccine be included as an option for MenACWY/MenB vaccination in
people currently recommended to receive both vaccines ?
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    2. Should pentavalent vaccine be included as an option for people currently recommended to
receive MenACWY only ?
3. Should pentavalent vaccine be included as an option for people currently recommended to
receive MenB only ?
In February 2023, the WG discussed the epidemiology of meningococcal disease in the United
States (US), Pfizer ’s MenABCWY vaccine clinical trials data, and the WG’s interpretation of
those data. In June 2023, the WG introduced the CDC ’s cost -effectiveness model and provided
a summary of the Grading of Recommendation s Assessment, Development, and Evaluation
(GRADE ) and Evidence to Recommendation (EtR) Framework.
Between June and October 2023, the WG received feedback during the June ACIP meeting. A
review of the meningococcal schedule has been postponed to allow for consideration of GSK’s
forthcoming pentavalent vaccine and availability of data about post-COVID meningococcal
epidemiology. The WG also reviewed comparisons of the cost-effectiveness models. The CDC
cost-effectiveness model has been updated with new price estimates. The price for pentavalent
vaccine was $40 to $90 more than MenB but is now similar , so there has been an adjustment.
The WG also discussed 3 potential recommendation options based on the concerns raised by
ACIP members in June and the new cost-effectiveness assessments.
To summarize where the WG is, there is strong consensus among the WG members for the first
policy question regarding whether pentavalent vaccine should be included as an option for
MenACWY/MenB vaccination in people currently recommended to receive both vaccines, which pertains to persons 16 to 18 years of age; it typically happens around 16 years. There was strong consensus among the WG members regarding the second policy question that the pentavalent vaccine should not be included as an option for people currently recommended to
receive the quadrivalent vaccine only, which pertains to the 7
th grade dose. There was limited
consensus among WG members about the third question that perhaps pentavalent vaccine should be included as an option for people currently recommended to receive MenB only . This
is the dose that typically is given just before college entrance or military service.
During this session, presentations were provided on the plan for revisiting the adolescent schedule for meningococcal vaccines, a comparison of the Pfizer and CDC cost-effectiveness
analyses for Pfizer’ s MenABCWY vaccine , a summary of the EtR Framework and proposed
recommendations for Pfizer’ s MenABCWY vaccine, and a vote and the Vaccines for Children
(VFC) Resolution.
Plan for Revisiting Adolescent Schedule for Meningococcal Vaccines
Lucy McNamara, PhD, MS (CDC/NCIRD) provided a brief update on the meningococcal
vaccine WG’s plans for revisiting the adolescent schedule for meningococcal vaccines over the
next year. As mentioned earlier, a great deal of interest was expressed during the June 2023
ACIP meeting in revisiting the current meningococcal vaccine schedule for adolescents. Some
of the questions that were raised regarded whether the dose of MenACWY at 11 to 12 years of
age is still needed, especially given recent epidemiology of very low disease burden among
those 11─ 15 years of age. There also were some questions around the shared clinical decision-
making recommendation for B vaccines. It was noted that the availability of pentaval ent
meningococcal vaccines may complicate the shared clinical decision-making discussion for
providers and that some nuances , such as the projected short duration of serogroup B
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    protection may be lost, when it is possible to give a single injection covering all 5 serogroups. It
also was highlighted that opportunities to reduce the total number of vaccines given, by
leveraging pentavalent vaccines for instance, would be appealing if it is possible to still maintain
a high level of protection. The WG considered this feedback and decided to incorporate
revisiting the adolescent schedule into its work plan over about the next 15 months.
There are a number of reasons that the WG is planning to spread this evaluation out over that timeframe rather than trying to push to accomplish it more quickly. The WG would like to ensure
that there is adequate time to complete and fully evaluate the necessary GRADE and EtR assessments, including addressing questions about cost-effectiveness and the importance of
the booster response for what currently is the second dose of MenACWY vaccines for
protecting older adolescents. The WG anticipates being able to assess the extended interval
data for pentavalent vaccines administered more than a year apart at some point during 2024,
which will open new options for spacing of meningococcal vaccine doses. The WG wants to
make sure that there is plenty of time to integrate the recommended changes into the overall
Child and Adolescent Immunization Schedule in a way that will be clear to clinicians. In addition,
the WG wants to ensure that they can fully consider an additional year of post-COVID
epidemiology, which they feel is particularly important in light of the new meningococcal strains
in the US that are primarily affecting Black and Hispanic populations and have substantial
implications for health equity.
While there are many ways the adolescent schedule for meningococcal vaccines could be
altered, the WG plans to focus on the following core questions based on the input from the last
ACIP meeting:
1. Should the MenACWY series recommendations be changed to begin at an older age than
currently recommended at 11─12 years of age, to eliminate the dose recommended at
11─12 years of age of MenACWY entirely, or to revise the recommendation to shared
clinical decision-making?
2. Should the MenB series recommendations be changed to alter the recommended ages or dosing interval to provide better protection for individuals 18─19 years of age, or should the shared clinical decision- making recommendation be revisited for some or all
adolescents(e.g., those planning to attend college)?
3. Are there ways to better integrate the MenACWY and MenB vaccine schedules to streamline administration and increase feasibility for providers ?
The WG established a tentative timeline for addressing these questions over the next 4 ACIP
meetings. In February 2024, the plan is to return to the committee, recognizing that there may
be a number of new members at that time, with more detailed terms of reference (TORs) for
addressing the schedule change. In June 2024, the WG hopes to present epidemiologic
analysis that are relevant to possible schedule changes, including understanding the burden of
disease currently averted by the MenACWY dose at 11─ 12 years of age; assessment of racial
and ethnic differences in disease burden among adolescents ; an analysis of the risk factors for
serogroup B meningococcal disease among college versus non-college students ; an update on
breakthrough meningococcal disease cases in vaccinated individuals to inform the thinking
around duration of protection of the vaccines ; and tentatively extended interval data for
administering 2 doses of pentavalent vaccines several years apart if they are available by that
point. In October 2024, the WG plans to cover the GRADE and EtR assessments for proposed
changes to the adolescent schedule and a cost -effectiveness analysis for changes to the
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 MenACWY and MenB adolescent schedules . The WG hopes to have votes during February
2025. In addition, the WG also anticipates addressing upcoming policy questions related to an
additional pentavalent vaccine for which there is not yet a set timeline. The hope is to remain
somewhat flexible to ensure that the WG can appropriately integrate, review, and discuss the
additional pentavalent vaccine within the broader schedule change discussion.
Discussion Points
Dr. Daley inquired as to whether there is an ability to assess competing priorities. The
increasing complexity of the schedule can have negative side effects, such as challenges for providers in terms of knowing what to stock. For instance, a family medicine practice will be immunizing birth to older ages. Consideration will have to be given to number of products to stock, whether switches can be made from one product to another, how decisions will be made
about who should be vaccinated in an environment with clinical decision support versus one
without, whether larger refrigerators will be needed to stock the various vaccine products, et cetera. There could be benefits to simplification that would then translate to other vaccine-preventable diseases.
To Dr. McNamara , this would fall under the “feasibility” component of the EtR Framework and
definitely could be considered in the WG deliberations. She invited suggestions and resources
for data or evidence relevant to any proposed strategies in terms of how changes in t he
meningococcal vaccine schedule could affect overall feasibility in the clinical setting.
Dr. Talbot said she felt like they were doing this out of order. It seemed peculiar to vote for a
new vaccine, re-evaluate this in a few months, change the schedule, and then vote again. If
they wait to re-evaluate the vaccine, when to administer it, how much is needed, et cetera, the decisions would be clearer and less complicated for primary vaccinators. It will not help vaccination rates to make a decision during this meeting only to change it in 3 months. She suggested not voting on this vaccine until they know what schedule will be recommended.
Given that there currently are vaccines to cover these pathogens, there is no hurry to do this.
This differs from the hurry during COVID when people were dying and hospitals did not have enough staff, rooms, and ventilators. Therefore, she did not see the hurry for voting during this session.
Dr. McNamara agreed with this point and explained that this is a big part of why the WG framed
the PICO questions the way they did for the pentavalent vaccine. The intent pertained to
whether the pentavalent vaccine could be swapped in basically as a part of the exist ing
recommendations, not to change any of the existing recommendations for ACWY or B vaccines. At this juncture, the point is to let people know whether they can use the pentavalent vaccine in lieu of already recommended doses. The pentavalent vaccine was recently licensed and
typically, ACIP evaluates vaccines after they are licensed. She deferred to the ACIP Secretariat to discuss whether there truly is a hurry. The vaccine was licensed last week.
Dr. Wharton indicated that it would be up to ACIP about whether there would be a vote. A
motion and second would have to be made in order to move forward on a vote. As Dr. McNamara commented, the intent of this proposal was to provide a recommendation for use of
a licensed vaccine in the context of the current schedule upon which ACIP would vote the next
day. A potential change in the current recommendations would clearly be a longer conversation. In the meantime, an ACIP vote would allow providers to use this recently licensed product within the context of the current schedule.
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  Ms. Arthur (BIO) reminded the committee that because of the 21st Century Cures Act (Cures
Act) that was passed a few years ago, there is a statutory obligation that newly licensed
vaccines be evaluated and voted upon relatively close to their licensure at the nearest ACIP
meeting.
Dr. Kimberlin (AAP Redbook) said that in his personal view, he thought it was good that the WG
would be evaluating the meningococcal schedule over the next 18 months. He thinks it is always good to look for ways that things that have evolved over many years could be
streamlined and perhaps improved upon based upon current data. His recommendation would
be to try to avoid shared clinical decision-making recommendations. Increasingly, he is hearing from providers in the field that these do not really help. If, after 18 months, the WG cannot make a decision, it is unclear how a private practice pediatrician is supposed to do the same with much less information and much less time to do the deep dive than the expert ACIP members
were able to do.
Ms. Howell (AIM) acknowledged that while the ACIP does not determine immunization
requirements for school s, many states have 7
th grade requirements or requirements around
meningococcal vaccine for children 11─12 years of age. If this change is made, states probably
would have to change legislation or rules. She expressed her hope that the WG would take this
into consideration.
Dr. Long agreed with Dr. Talbot that it would be difficult for the ACIP to talk about the current
vaccine , because everything would be flavored by what they think about the schedule and the
use of meningococcal vaccines. Perhaps they should table this discussion until at least they
hear the cost-effectiveness data because that may alter what they want to do.
Dr. Poehling emphasized that the WG has really spent a lot of time thinking about what the most
cogent and efficient way to move forward would be. The question regards whether they have all
of the information they need or would like. She said she would like to make the argument that they had enough information to make a decision during this meeting and that with the FDA ’s
approval of this vaccine, no recommendation would mean that people would have to make
decisions with no guidance. In her opinion, it would be better to have ACIP guidance.
Dr. Fryhofer (AMA) noted that her comment was triggered by Dr. Daley ’s comment about
competing priorities, complexity, and storage challenges. As increasingly more vaccines are
recommended, she encouraged pharmaceutical companies to make small quantities of
vaccines available for purchase rather than making a minimum of tens, hundreds, or thousands
of doses. That would increase access to vaccination.
Comparison of Pfizer and CDC Cost -Effectiveness Analyses
Ismael R. Ortega-Sanchez, PhD (Senior Health Economist, CDC/NCIRD) discussed the
economics of the potential pentavalent meningococcal conjugate vaccine, comparing and
summarizing key elements and findings of 2 economic models (Pfizer and CDC) on the use of
pentavalent vaccine for the prevention of invasive meningococcal disease (IMD) among US
adolescents. In the previous 8 to 9 months, the 2 models were updated several times. They also
were discussed extensively with the ACIP Meningococcal WG. For full disc losure, Dr. Ortega-
Sanchez indicated that he led the team conducting the CDC model.
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 The 3 policy questions centered on analysis by both models are listed here:
1. Should the pentavalent vaccine (MenABCWY) be considered as an option for
MenACWY/MenB vaccination in people currently recommended to receive both vaccines? (PICO 1)
2. Should the pentavalent vaccine (MenABCWY) be included as an option for people currently recommended to receive MenACWY only? (PICO 2)
3. Should the pentavalent vaccine (MenABCWY) be included as an option for people currently recommended to receive MenB only? (PICO 3)
In general, the goal is to answer whether the new pentavalent vaccine should be considered as
an option for the quadrivalent and MenB vaccination in people currently recommended to receive both vaccines. The starting point of the 2 economic models are the policy questions
regarding potential recommendations for the use of pentavalent vaccine in adolescents. To consider the economic s of each policy question is to consider simultaneously the health benefits
and cost of vaccination by answering the question, “Is vaccinating adolescents with the
pentavalent (MenABCWY) vaccine series to prevent invasive meningococcal disease in
adolescents cost-effective relative to the use of quadrivalent and MenB vaccines?” To address
this question, the 2 models used the same comparator (e.g., the current standard of care). The
current standard of care and the hypothetical vaccines and vaccination strategies (interventions) in the model are labeled using the initials of the vaccine and serogroups contained in the dose, which are as follows:
To have a visual about the comparisons of the Pfizer and CDC incremental analysis included in
the 2 models being compared, the table below describe the alignment of this incremental cost-
effective analysis with the policy questions to be answered. An important and recurring detail in
this presentation is the price of a dose of pentavalent used as input in the specific incremental analysis :
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The policy questions have important implications for the 3 groups of elements included in the
models. The comparison of the 2 economic models focus es on how appropriate the selection of
the modeling approach is, the inputs, and the assumptions —especially those that are strong
influential assumptions. In general, the 2 models follow similar designs with the use of a static
analytical decision-making approach, reliance on probabilistic or deterministic sensitivity
analysis to manage the various data uncertainties, a hypothetical cohort of adolescents ≥ 11
years of age in the US, a timeframe of the first 15 years after 11 years of age to account for the
vaccination schedules , loss of income associated with temporary productivity loss and
premature mortality associated with meningococcal disease.
Once the modeling strategies were set, the 2 models were fed with different types of input data
(e.g., epidemiologic, vaccine characteristics, healthcare resource utilization (HCRU) and cost,
indirect cost quality of life, and other parameters). Across models, the sources, specific values,
and assumptions of the parameters have some overlaps, but they were marked as different as well. In the boxes are the standard outcomes estimated and reported by the 2 models , though
the presentation focused primarily on the cost per quality -adjusted life year (QALY ) saved or the
incremental cost-effectiveness ratio (ICER):
Selected inputs for this comparison focused on the cost of the vaccine and vaccine administration, IMD incidence for the pre-vaccine and in vaccine era, initial vaccine
effectiveness (VE) and waning over time, IMD-associated permanent sequalae, age and
serogroup-specific Case Fatality Rate (CFR), and acute IMD QALY scores and unitary direct
costs .
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  From March 2023 to June 2023, Pfizer submitted various technical reports using the
pentavalent vaccine price of $240 with a range of $230 to $250 per dose. In August 2023, Pfizer
submitted a new technical report updating the pentavalent price to $250 for the private cost per dose and $187.50 for the public price . In October 2023, Pfizer submitted a newer technical
report updating the pentavalent prices for the strategies using 2 doses for pentavalent of $210
for the private sector and $157.50 for the public sector. For the strategies with a single dose of
pentavalent, the price remained at $250. This distinction is very important in terms of analyzing
the specific outcomes estimated in each of the models. Regarding the various components of the vaccination program beyond the price per dose, v accine costs were differentiated based on
the 2023 public and private sector prices and vaccine administration settings for vaccines already available in the vaccination schedule. Ranges were estimated from public and pri vate
vaccine prices and the cost of administration by site. Pentavalent was calculated using the
hypothetical range of prices as released by Pfizer for the pentavalent vaccine in August and in
October 2023. Although not included in these costs, in the CDC model, rates of moderate and severe adverse events (AEs) were taken into account using publications in the literature. Only
the CDC model considers vaccine wastage for open vial, mishandling, or outdated shelf life.
Another significant component in the total estimation is vaccination program costs.
In terms of the average annual incidence in v accine serogroups BCYW by age per 100,000
used in the models based on ABC Core Surveillance and the National Notifiable Diseases Surveillance System (NNDSS), rates of IMD remained relatively higher in late adolescents. But
in general, rates have been declining for all ages. Overall, the incidence rates are 1/6 of those from the recent pre-vaccine era. In terms of the marked differences in the models, the CDC
model used age by year IMD incidence data showing the peak in the late adolescent years,
while the Pfizer model used only 4-year averages. Moreover, Pfizer extrapolated the average
rates from late adolescents to the early 20s. This approach may underestimate the incidence in 10 years and overestimate the incidence in early 20 years.
The initial VE by vaccine dose and serogroup are critical data inputs to assess the vaccination
impact of the strategies. Value and assumptions on initial protection are based on value
sources.
1 The pentavalent is based on the Phase 3 noninferiority initial VE by a single dose at
11 to 12 years of age and a second dose at 16 years of age of pentavalent vaccine as reported
by Pfizer. For quadrivalent and MenB, the initial VE was based on effectiveness surveillance.
One of the key assumptions following initial VE was related to the duration of protection. This
assumption was differentiated by serogroups containing the vaccine. Assumptions on vaccine
protection were more conservative in the CDC model. There was a fast decline in waning of
vaccine protection in the CDC model for both the quadrivalent and MenB vaccines. For the
Pfizer model, there was an assumption based on vaccine protection as being persistent to about
4 to 5 years for a single dose of pentavalent based on the hSBA from the Pfizer clinical trial
report. In the CDC model, the duration of protection for pentavalent vaccine was assumed to
follow quadrivalent vaccine, while the duration of protection for MenB for a single dose and 2 -
dose and for the pentavalent was assumed to be following the MenB vaccine. There was
1 Phase 3 noninferiority initial vaccine efficacy by single dose (at 11-12yrs) and second-dose (16yrs) of pentavalent (Men ABCWY)
vaccine as reported by Pfizer (data on file); Updated Pfizer Technical reports on Cost-effectiveness of the Pentavalent
Meningococcal Vaccine (MenABCWY) in the US; Cohn AC, MacNeil JR, Harrison LH, et al. Active Bacterial Core Surveillance
(ABCs) Team and MeningNet Surveillance Partners. Effectiveness and Duration of Protection of One Dose of a Meningococcal
Conjugate Vaccine. Pediatrics. 2017 Feb;139(2):e20162193. doi: 10.1542/peds.2016-2193. PMID: 28100689; PMCID: PMC8353579; *The range for VE efficacy for first dose of MenB is from Castilla et al. NEJM 2023
https://www.nejm.org/doi/full/10.1056/nejmoa2206433
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 uncertainty of the waning assumption beyond available surveillance of Phase 3 data. The CDC
model tried to minimize the inclusion of that uncertainty into the model , whereas the Pfizer
model still showed substantial protection that also influence d the estimates in the end of the
cost-effective analysis.
As in previous analys es, the models used percent of survival cases with specific sequelae as
reported in the literature. The Pfizer model reports a larger number of long-term sequelae,
though there were some with zero value or close to zero probabilities. Over the range of
survivors with sequelae, approximately 28% suffer ed some long-term sequelae in the Pfizer
model. The CDC model focus ed on the most common long-term sequelae among survivors of
meningococcal disease infection for which there was a smaller probability of survivors with
sequela of approximately 21.6%. However, the CFR was very close at 12.5% in the Pfizer
model and the 12.3% in the CDC model . There was differentiation by age group in the Pfizer
model . The difference in the methodology was that in the Pfizer model included life years los t at
the end of life for those with sequelae who were included in the Pfizer model, which means that
for a specific sequela, multiple amputations, there was a reduction in life expectancy that was
accounted as the lif e years saved by the vaccination program.
Regarding medical cost and quality scores, Pfizer medical cost differentiated the type of IMD .
On average, medical costs could be twice as much as the costs used by the CDC model .
Regarding QALY scores, because meningococcal disease follows a rapid clinical course, both models estimated decrease in QALYs associated with the acute illness for survivors of IMD and
specifically for the cases without permanent sequelae. These values are different in magnitude. In the CDC model, the quality adjusted life days (QALD) was approximately 46.26 days during
the acute phase of the disease, which is only 1/3 to 1/4 of those used for a Pfizer model for the same acute phase during the acute phase of IMD . After the acute phase in cases without
permanent sequelae, the equivalent QALD was approximately 14 to 15 days in the CDC model,
which was approximately 1/6 the value used by the Pfizer model during the acute phase of the
IMD. In the CDC model, the values are more conservative than used by Pfizer.
In terms of a comparison of the outcomes reported by both models for each of the policy questions, among the main results were the total net cost impact and incremental cost-
effectiveness of vaccination studies (e.g., incremental health impact in terms of cases, deaths,
life years, and QALYs save d) and ICERs. In terms of PICO 1, the incremental effectiveness and
cost-effectiveness of vaccinating healthy adolescents 11-12 and 16 years old with p entavalent
vaccine relative to using MenACWY and MenB vaccines , a very important clarification is that to
make fair comparison, for the total net cost estimates , cost-saving, and cost per QA LY saved,
the analysis used $250 per private dose administered versus $187.50 for the public sector. The
cumulative probability of ICER per QALY saved for the CDC model, the 5
th and 95th percentiles
showed that the probability of being cost-saving is very high. CDC and Pfizer aim ed to answer
PICO 2, the incremental effectiveness and cost-effectiveness of vaccinating healthy adolescents 11-12 and 16 years old with p entavalent vaccine relative to using MenACWY only, using the
updated lower price per dose for the private sector of $210 and public sector of $157.50 for the
pentavalent vaccine. This analysis showed that the most important variables explaining the variability between the models were related to dis utilities and long-term sequelae. The C DC
model showed that the ICER also was costly at a higher level at more than twice that of the
incremental cost per QALY as reported by the Pfizer analysis. The incremental cost being
incrementally costly was correlated by the cumulative probability of simulations in the CDC
model, specifically in that both the 5
th and the 95th percentiles were positive. In other words, the
probability is quite high that in this strategy with 2 doses, the P -P-N is costly relative to the
standard of care.
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     Both models attempted to answer PICO 3 regarding the incremental effectiveness and cost-
effectiveness of vaccinating healthy adolescents ≥16 years old with Pentavalent vaccine relative
to using MenB vaccine only . The estimates of both the incremental health outcomes and net
cost were compared to be similar relative to the standard of care and coincide in pointing that
the Q -P-P would be cost -saving. This fact was corroborated by the cumulative probability of
simulations in the CDC model in that the 5th and 85th percentile were negative, meaning that
they are cost-saving. These estimates used the updated vaccine price of $210 for the private
sector and $157.50 for the public sector.
Among the limitations are first that factors not considered in the Pfizer and CDC model s may
result in overestimating the ICER or underestimating the cost -effectiveness of the pentavalent
vaccine. In the base-case, both models assumed no protection against non-IMD and no indirect
protection against IMD of unvaccinated individuals because they used only a discrete model not
a dynamic model with high immunity components or indirect effects. Productivity losses incurred
by caregivers for long-term specific sequelae were based on assumptions and were partially
included. Second, differences in key inputs among the Pfizer and CDC model s and the
uncertainty in input data may explain some of the difference in the results, although it is very
interesting to see that there are coincidences as well. The most important elements that drive the difference among these 2 models is the duration of vaccine protection, medical costs ,
variability in IMD incidence and CFR data, inclusion of different sequalae, and QALY score for
IMD cases without permanent sequelae. Third, the pentavalent price for Q -P-B is uncertai n. The
price used in this analysis was the minimum expected cost as reported by Pfizer. Higher prices will increase total net cost and ICERs .
In conclusion, in both models, pentavalent vaccine would reduce the IMD burden in
adolescents. In both models, strategies with 1 or more doses of the pentavalent vaccine would
save more or an equal number of IMD cases. For PICO 1, Q -P-B could be incrementally cost-
saving relative to the standard of care, remembering that in this strategy, a dose of pentavalent
would be substituted for the second dose of the quadrivalent and the first dose of MenB. For PICO 2 , the strategy that includes 2 doses of pentavalent and nothing else, is incrementally
costly, not cost-saving , relative to the standard of care of 2 doses of quadrivalent. For PICO 3 ,
the model with a quadrivalent followed by pentavalent at 16 years of age and another dose 6
months after pentavalent , is likely cost -saving relative to the standard of care. About 96% of
iterations in the CDC model simulation have an ICER less than zero. Reasonable pentavalent
prices and duration of protection combined with careful design of vaccination interventions with pentavalent will determine the cost and cost saving value of the pentavalent vaccine among adolescents ≥11 year of age.
Discussion Points
Referring to Slide 12 regarding the cost of the pentavalent vaccine for the 2-dose option versus the single dose option, Dr. Loehr noted that the single dose option, Q -P-B, would be $250 and a
2-dose option (P-P-N and Q -P-P), would be $210. It seemed odd to him as a practicing
physician that Pfizer would charge a different amount based on what they decide. He would be purchasing vaccine for his office at a certain price, but they would not know how he is giving it.
Dr. Palumbo (Pfizer) responded that a simplified meningococcal vaccine schedule like Q -P-P
would improve vaccination administration and simplify stocking. Pfizer commit s to a list price of
$210 for a Q -P-P dosing schedule for any combination that includes a 2-dose schedule for the
Pfizer pentavalent vaccine as aligned with the label. In the scenario of a Q -P-B in isolation,
13

 given that this does not align with the FDA-approved 2-dose schedule, Prizer cannot commit to
a price at this time. The previously shared prices of $250 for private and $187.50 for public per
dose shared in Dr. Ortega-Sanchez's cost-effectiveness model was a minimal price for the
purposes of economic modeling.
Dr. Talbot observed that this would mean that if the ACIP voted for a Q-P-B strategy, this would
mean an off-label recommendation for the P and the B b ecause B is 2 doses.
Dr. McNamara responded that a Q-P-B schedule would be off-label for pentavalent and for B
because those are both licensed as a 2-dose series. However, as pointed out earlier, there is no
interchangeability between manufacturers of B components. The pentavalent and Trumenba®
contain the same component and should be able to be used interchangeably in terms of the
immune response, but it is off-label.
Dr. Poehling emphasized that cost -effectiveness is very important in thinking about this. She
asked Pfizer for clarification about how many doses are in a bottle and whether she was
understanding correctly that the price of the vaccine would vary if it could be used with both Bs,
and it could be used for 2 doses only if the ACIP said it could be used when both vaccines are
recommended.
Dr. Palumbo (Pfizer) responded that bottles contain a single dose and that in any Q-P-P
scenario or any combination where a Q -P-P is an option, the price will be $210 a dose. The
problem with the Q-P-B as already stated is that it is not aligned with the label , so Pfizer has not
considered or finalized pricing for that scenario. For any combination that includes Q-P-P the
price is $210 per dose. Dr. Poehling requested that since the ACIP was planning to vote during this meeting, she asked
the group to convene to come up with a price in case the vote goes a different way, because that is an important determination.
Dr. Cineas asked whether the standard of care used in both analyses , Q-Q and B-B, takes into
account the current B uptake in terms of the cost analysis since that is a shared clinical
decision-making recommendation.
Dr. Ortega- Sanchez replied that the 2 models used a static model, which means that only direct
impacts of vaccination were taken into account. In order to align both model s, a single similar
uptake of the vaccines was used so that variation was not included in the base-case analysis.
They can definitely include variations in uptake to determine whether that would be mute to the
incremental cost ratios , because whatever is saved in terms of not giving doses also is not
saved in terms of disease prevented and they cancel in the ICER.
Dr. Talbot asked the current price for 1 dose of B, even if giving 2 doses, when the vaccine is
purchased. In addition, she asked whether Pfizer was insinuating that if the ACIP changes the
recommendation to Q -P-B that they would change the price of B .
Dr. Palumbo (Pfizer) reiterated that the Q-P-B scenario does not align with Pfizer’s label, so
they would need to consider what the price would be given that. However, if there is an option of
Q-P-P or any combination where 2 doses of the pentavalent vaccine is an option in which case
the price would be $210 per dose.
14

  Dr. Talbot clarified that her question regarded the current cost of 1 dose and whether Pfizer
would consider changing the price of MenB with a Q-P-B scenario.
Dr. Palumbo (Pfizer) replied that the current cost for Pfizer’s MenB vaccine is $178 for private
and $130.77 public and that the current price for MenB vaccine would not change.
Dr. Lee said that in this instance, she appreciate s the manufacturer's approach in terms of being
transparent about the 2- dose pricing and recognizing that if it is not as it was originally licensed
for use, Pfizer would need to reconsider the pricing strategy. She also noted that while she
typically is not empathetic, she is empathetic in this instance. Nevertheless, this makes it very
difficult to make a decision. She thought the tension Pfizer was hearing was more about the fact
that the ACIP has to consider cost-effectiveness in any of its decision-making . The uncertainty
around the price makes it difficult to assess that, even though there are some ranges and some
sensitivity analyses.
Dr. Goode (APhA) asked why the P -P-N, which is no extra intervention, would be more costly
than a Q -P-P.
Dr. Ortega- Sanchez indicated that for PICO 2, the Pfizer analysis includes the number of cases
incrementally of IMD cases saved, IMD deaths saved, and life years saved, but the cost is
basically due to the new pentavalent vaccine price compared to the cost of the standard of care
(P-P-N versus Q -Q). When only pentavalent and nothing else is used against the standard of
care of 2 doses of quadrivalent vaccine, it becomes costly. In the CDC model for PICO 2, the
same analysis was used with the same assumptions and data, but the total per QALY saved
was higher ($4.7 million) than the one provided for Pfizer ($1.94 million). All simulations,
regardless of which ones are positive , means that it will be costly .
Dr. Talbot observed that if P-P-N is used currently with the recommendation of 11 and 12 years
of age, her understanding was that it would not provide B protection in college. However, if P -P
is given starting at 16 years of age, that would cover college. Her questions regarded whether P-P-N is cost-effective, but not for B when one gets to college because a B booster would be
required at that time.
Dr. Ortega- Sanchez indicated that because the effectiveness of P -P starting at 11 years of age,
because of the cost the pentavalent vaccine and because they look very similar in terms of
effectiveness, the strategy of substituting the quadrivalent with the pentavalent is more costly,
not c ost-effective. If that is switched to give the 2 pentavalent doses at 16 years of age, that is a
different question that was not analyzed in these strategies. It was one of the analyses they
were thinking of doing, but that is a different type of question.
Dr. Long asked what percentage of older adolescents currently get B vaccine under shared
clinical decision-making and said she assumed the majority of them are college students.
Dr. McNamara indicated that the last data show that about 30% of those 17 years of age are
getting at least 1 dose of serogroup B vaccine. Other data sources show that a little more than
50% of those complete the series . Unfortunately, there are not good ways to assess whether
the majority are college students.
15

   Dr. Long emphasized that doctors do not like to have to stock many different kinds of vaccines,
so the least difficult would be to use the combination vaccine. She asked whether the cost-
effectiveness model took into account that there potentially would be a much higher percentage of MenACWY uptake at this age.
Dr. McNamara indicated that the current MenACWY uptake is in the high 80% range for dose
given to adolescents at 11 to 12 years of age and about 60% for completion of the 2-dose
series . There are some data from administrative claim sources that have demonstrated that the
actual proportion of those 16 to 18 years of age who are current with catch-up
recommendations is significantly higher than that as some people don’t get the 11-12 year old dose but get it later .
Dr. Long asked whether the cost-effectiveness model figured in that since the default position
would be much less shared clinical decision-making and a much higher percent getting the
combination vaccine .
Dr. Ortega- Sanchez reiterated that these are static models that include only direct impact of
vaccination. In this this type of analysis, uptake is mute in terms of impact on the cost-
effectiveness ratio. While not giving the vaccine saves dollars, this also does not save the
disease. Therefore, both of those values, one in the denominator and one in the numerator,
cancel and that is why the ICER s and cost per QALY saved remain unchanged and are not
influenced by the coverage or the uptake of the vaccination.
Dr. Long emphasized that the unintended consequences of not preventing disease would be
extremely costly.
Dr. Lee added that the implication would be that the total cost would be higher , but that does not
necessarily impact the cost-effectiveness. She reminded everyone that the ACIP C harter
specifically states that the committee consider cost-effectiveness and not necessarily total cost
in its decision -making.
Ms. McNally asked whether Pfizer could discuss how a shared clinical decision-making
recommendation may impact their pricing decision, if at all. Dr. Palumbo (Pfizer) indicated that this would not impact their pricing decision and reiterated
that when she talks about “in combination,” if a Q -P-P and a Q -P-B are recommended, the price
would be $210 per dose. It is the Q -P-P in isolation that does not align with the label, which they
would need to reconsider.
Pfizer Statement
Dr. Luis Jodar (Chief Medical Officer for Pfizer Vaccines/Antivirals and Evidence
Generation) emphasized that to be clear so that there are no misunderstandings, when talking about Q -P-P, this is a licensed 2-pentavalent product administered 6 months apart. Once the
licensed option is included, other options that include a pentavalent followed by a monovalent B
are at the same price. It is only the situation in which there is a mixed schedule that is not in the
label, which is a pentavalent and monovalent B, is exclusively recommended when the price
needs to be reassessed. To highlight the advantages of a recommendation with the
quadrivalent at 11 years of age followed by 2 doses of the pentavalent (PENBRAYA™) at 16
years of age given 6 months apart identified as Q -P-P, Pfizer developed PENBRAYA™ in line
16

   with the CDC ’s General Best Practice Guidelines for Immunization.2 In general, he said he
thought they all could agree that licensed combination vaccines can improve vaccine uptake,
vaccine compliance, and reduce the number of injections individual s receive. Recommending 2
doses of PENBRAYA™, the Q-P-P strategy , would simplify the current standard of care by
reducing the number of injections from 4 to 3 to help protect adolescents and young adults
against all 5 serogroups . This strategy can be accomplished by stocking only 2 vaccines,
whereas the mixed Q -P-B strategy would require healthcare providers ( HCPs ) to stock 3
vaccines (e.g., quadrivalent, pentavalent, and monovalent B vaccines ). This would add
complexity, costs , and the potential for errors.
Additionally, administration of the monovalent MenB vaccine is not necessarily equitable across
the US with adolescents residing in rural areas and Black and Latino adolescents having lower coverage. Pfizer’s believes that PENBRAYA™ is a tool that could at least help close these
equity gaps. The 2 doses of PENBRAYA™ are given 6 months apart, which is the schedule
based on the clinical data and the only one that is aligned with the FDA label. It is estimated that
implementation of 2 doses of PENBRAYA could prevent more cases and deaths caused by IMD
compared to the current standard of care. The proposed Q -P-P schedule will reduce costs
compared to the current standard of care. PENBRAYA ™ will cost approximately 43% less than
if the ACWY and B vaccines are administered separately. That was why Pfizer wanted to
emphasize this price. In fact, Pfizer is committed to making the vaccine available at a similar
price to an individual MenB vaccine, thus ensuring that the FDA indicated use of 2 doses is the most cost-sav ing option for the meningococcal vaccine program.
Dr. Jodar respectfully urged the ACIP to take up this policy and make recommendations of the
use of the pentavalent meningococcal vaccine during this meeting. HCP around the country
look to the ACIP as experts that set the standards of practice. Silence from ACIP until 2025 will
have negative effects on vaccine confidence and avoid information where suboptimal practices
can emerge. Recommendations from ACIP should ensure on -label use of the vaccine and will
result in better real -world safety and effectiveness data over the next year that the ACIP
campaign used to revisit recommendation on the entire meningococcal platform. He thanked the
committee for these complex deliberations to optimize the meningococcal vaccine platform and
expressed hope that the simplicity , advantages, and cost savings of the Q-P-P strategy can
translate into public health benefit and accessibility to everyone.
Dr. Kimberlin (AAP Redbook) asked if on slide 18, is SOC in the table Q -Q + B -B?  And on slide
21, what is SOC? Dr. Ortega- Sanchez indicated on slide 18, it is Q -Q+B -B, and on slide 21 it is Q -Q+B -B.
Summary of EtR and Proposed Recommendations for Pfizer’s MenABCWY Vaccine
Dr. Jennifer Collins (CDC/NCIRD) presented a summary of the EtR framework and the
proposed recommendation for Pfizer ’s MenABCWY vaccine. As a reminder, current ACIP
recommendations for meningococcal vaccines are as follows:
Routine Schedule
MenACWY: dose 1 at age 11– 12 years, booster dose at age 16 years
MenB (shared clinical decision-making): 2 doses at age 16– 23 years (preferred age 16– 18
years)
2 https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/index.html
17

S
pecial Situations
Meningococcal vaccines that are licensed and available in the US are interchangeable and
include:
MenB vaccines are not interchangeable, and include:
Pfizer's pentavalent MenABCWY vaccine is now licensed as a 2-dose series with a 6- month
interval for individuals aged 10─ 25 years. As a reminder, the pentavalent vaccine is comprised
of Trumenba™, Pfizer's MenB vaccine that is currently licensed and available in the US, and Nimenrix ™, Pfizer’ s MenACWY vaccine that is not licensed in the US, but has been used
extensively in Europe and elsewhere for more than a decade.
The Meningococcal WG addressed 3 policy questions for the following PICOs:
1. Should the pentavalent vaccine be included as an option for MenACWY/MenB vaccination
in people currently recommended to receive both vaccines? (PICO 1)
2. Should the pentavalent vaccine be included as an option for people currently recommended
to receive MenACWY only? (PICO 2)
3. Should the pentavalent vaccine be included as an option for people currently recommended to receive MenB only? (PICO 3)
18

 The population is individuals aged 10 years or older currently recommended to receive
MenACWY+MenB, MenACWY, or MenB vaccine . The intervention is vaccination with Pfizer ’s
pentavalent vaccine. The comparison varies by the policy question. The 6 outcomes that were
assessed through the GRADE process include:
1. Meningococcal disease caused by serogroups A, B, C, W, and Y (as appropriate by PICO)
2. Short-term immunity
3. Persistent immunity
4. Interference with other recommended vaccines administered concurrently
5. Serious adverse events (SAEs)
6. Non-serious AEs
This table shows how the PICOs were translated into schedule options for healthy adolescents
for the purposes of the GRADE assessment and the economic analysis. As a reminder, Q stands for the quadrivalent vaccine (MenACWY ), B for MenB, and P for the pentavalent
vaccine :
Recall that these options assumed that vaccinations were given first at ages 11─12 years when
the first quadrivalent dose is recommended, with subsequent vaccinations at age 16 years when
the second quadrivalent dose is recommended. However, as discussed during the June ACIP
meeting and earlier during this meeting, 16 years of age often is not optimal timing for the MenB
component. To summarize the WG consensus presented during the June 2023 ACIP meeting,
the WG was in favor of PICO 1 or Q -P-B. The WG was not in favor of PICO 2 or P -P-B. The WG
was divided regarding PICO 3 or Q-P-P. Since that time, the WG refined the EtR framework and
further considered possible implications of each PICO, especially PICO 3, based on concerns
raised by ACIP members during the June 2023 meeting regarding the following:
Cost-effectiveness concerns about all options, including the current schedule
Concerns about increasing exposure to B component vaccines related to reactogenicity, low
burden of disease, and limitations to protection
The concern that the optimal timing of B component is often not age 16 years
Fidelity to clinical trial data, licensure, and stocking concerns
Stocking and administration considerations
As presented earlier, the cost-effectiveness analysis was revised to reflect updates to the quoted price of the pentavalent vaccine and to incorporate refinements to the CDC model.
19

  To summarize the updated EtR, for the public health problem domain, members noted that the
incidence of meningococcal disease is low and decreasing, but that it causes very severe
disease and poor outcomes even with treatment. The case fatality rate is 10% to 15% and 10%
to 20% of survivors have permanent sequelae. The WG interpretation for public health problem for all three PICOs was that yes, meningococcal disease is a problem of public health
importance.
Regarding benefits and harms, 3 randomized control trials (RCTs) studied the pentavalent
vaccine 2 dose intervals (0, 6 months and 0, 12 months) versus MenACWY -CRM 1 dose +
MenB -FHbp 2 doses (0, 6 months) . The studies were conducted among both ACWY -naïve and
ACWY -primed participants. Available data facilitated assessment of select outcomes through
GRADE . Other important benefits and harms were not assessed through GRADE but were
factored into the WG interpretations. These included increased reactogenicity of MenB relative
to MenACWY and limitations to B protection, including that low VE is expected following a single
dose, rapidly waning protection following a 2-dose series , and multiple studies demonstrating
that MenB vaccination has no effect on meningococcal carriage.
To summarize the GRADE assessment for benefits, no data were available to assess the critical
outcome of meningococcal disease caused by serogroups A, B, C, W and Y. For the critical
outcome of short-term immunity, data were available from 1 RCT. Serogroup-specific
seroresponses 1 month after the first trial dose of ACWY - or B-containing vaccine occurred as
often or more often in the pentavalent group compared with the control group. The evidence
type was moderate for healthy persons and low for those at increased risk. For the important
benefit of persistent immunity, d ata were available from 2 RCTs . Seroresponse rates by
serogroup were similar between groups. The evidence type was low to moderate for healthy
individuals depending on serogroup and low for those at increased risk. For the critical outcome
of SAEs, data were available from 3 RCTs . Significantly more SAEs occurred in the pentavalent
group versus the comparison group, though none were attributed to the vaccine. The evidence
type was low for healthy individuals and very low for those at increased risk. For the important
outcome of non-serious AEs, data were available from 3 RCTs . Significantly more non-serious
AEs occurred in the pentavalent group versus the comparison group. The evidence type was
low for healthy individuals and very low for those at increased risk. No data were available to
assess the important outcome of interference with other recommended vaccines administered
concurrently.
For PICO 1, the WG interpretation was that the desirable and undesirable anticipated effects
were small, and they favored the intervention, with overall certainty varying by group. For PICO
2, the WG interpretation was that the desirable anticipated effects were minimal to moderate,
undesirable anticipated effects were minimal or small, and the balance favored the intervention,
comparison, or both and overall certainty varied by group. For PICO 3, the WG interpretation
was that the desirable anticipated effects were minimal, the undesirable anticipated effects were
minimal or small, and the balance favor ed the intervention or comparison. Overall certainty
varied by group.
Regarding the values of the target population, limited data were available. The WG noted that
among adolescents during 2021, vaccination coverage of at least 1 dose was 89% for
MenACWY and 31% for MenB. Limited data were available on vaccine uptake in other
individuals recommended to receive MenACWY or MenB vaccine. In general, use of combination vaccines can reduce the number of injections and is generally preferred over
20

 separate injections of the equivalent component vaccines.3 For the first values domain question
regarding whether the target population feel s that desirable effects were large relative to
undesirable effects, the WG interpretations were “probably yes ” for PICOs 1 and 2 and
“probably yes ” or “don't know ” for PICO 3. For the second values domain question regarding
whether there is important uncertainty or variability in how much people value the main
outcome, the WG interpretation was “probably no” for PICO 1 and “probably yes ” for PICOs 2
and 3.
For the acceptability domain, limited data were available. The WG noted that acceptability likely
depends on the PICO and balance of stakeholder values. HCP are likely supportive of options
that allow stocking fewer vaccines. Pentavalent vaccines have the potential to increase
vaccination rates against serogroup B disease and can reduce the number of injections from 4
to 3 for some patients. However, pentavalent vaccines also have the potential to incentivize
MenB administration at 16 years of age with waning immunity by the time of peak risk for some
patients. Many providers prefer to wait until closer to exposure to congregate settings , such as
college or the military. ACIP and WG members also have expressed concerns about increasing
exposure to MenB component vaccines , which are more reactogenic than MenACWY vaccines,
particularly when the burden of MenB disease is already low despite low vaccine coverage. The
WG interpretations for acceptability were “probably yes ” or “yes” for PICOs 1 and 2 and “don't
know” for PICO 3.
For the resource use domain, ACIP and WG members have noted that all proposed
meningococcal vaccine strategies are expensive, including currently recommended options for
adolescents. With the new price estimates, Q -P-P is the most cost-effective option when MenB
protection is desired. The WG interpretations were “probably yes ” or “yes ” for PICO 1, “probably
no” or “no” for PICO 2, and “probably yes ” or “yes ” for PICO 3.
For the equity domain, limited data were available. WG members felt that the pentavalent
vaccine is not expected to negatively impact equity. It potentially could reduce disparities among
those who might be interested in being vaccinated against serogroup B, but who might not otherwise receive clinical care that includes discussion of the MenB vaccine. WG members also discussed the possible risk of clinics not stocking monovalent B vaccines with some policy options , which could affect availability for outbreaks and for people at increased risk of
meningococcal disease who are recommended to receive 3 doses of MenB-FHbp. The WG
interpretations for equity were “probably no impact” or “varies ” for PICO 1, ”probably increased,”
varies,” or “ don't know” for PICO 2, and “don't know ” for PICO 3.
Regarding whether the intervention is feasible to implement, the WG felt challenges with
insurance coverage specific to the pentavalent vaccine are not expected. Substantial financial
burdens for providers or health systems also are not expected. The pentavalent vaccine would
provide an additional option in the current schedule and may reduce the number of doses for some people. However, administration requires reconstitution, which may lead to administration errors. St ocking 3 different meningococcal vaccine types also may be prohibitive for some
providers. The lack of B vaccine interchangeability complicates stocking considerations. The
WG interpretations for feasibility were “probably yes ” or “yes ” for all 3 PICOs.
3 General Best Practice Guidelines for Immunization. Best Practice Guidance of the ACIP. https://www.cdc.gov/vaccines/hcp/acip-
recs/general-recs/downloads/general-recs.pdf ; and American Academy of Pediatrics. Red Book 2018. Report of the Committee on
Infectious Diseases. 31st Ed. https://seciss.facmed.unam.mx/wp-content/uploads/2021/02/Red-Book-31th-Edition.pdf
21

 To summarize the EtR domains and WG interpretations for each of the 3 PICOs , for PICO 1
WG judgements were generally supportive, less so for PICO 2 with more uncertainty, and PICO
3 had the most uncertainty. A summary of the WG consensus and debate regarding the PICOs
is shown here:
Strong consensus in favor of PICO 1: MenABCWY as an option for MenACWY + MenB
(QPB)
Strong consensus against PICO 2: MenABCWY as an option for MenACWY only (PPB)
Limited consensus regarding PICO 3: MenABCWY as an option for MenB only
The options the WG debated for PICO 3 included the following:
Option A: Reject PICO 3 outright
Option B: Accept PICO 3 with limitations allowing for Q -P-P only
Option C: Accept PICO 3 fully, which would allow for Q -P-P and other options
This differentiation between Options B and C is new since June. In terms of the existing recommendations for the routine schedule incorporating shared clinical decision-making, the
first dose of quadrivalent vaccine is recommended at 11 to 12 years of age with a second dose
at 16 years of age. Shared clinical decision-making may result in no B vaccination , B
vaccination at age 16 years, or B vaccination at an age greater than 16 years. Although this is
relatively straightforward, introduction of the pentavalent vaccine adds complexity. Option A
adds Q -P-B to the existing options. That is , per the consensus in favor of PICO 1, the
pentavalent vaccine could be given in lieu of MenACWY and MenB when both vaccines are
indicated. Because PICO 3 is rejected with Option A, the pentavalent vaccine would not be used
in lieu of MenB only. The remaining MenB vaccine would therefore be monovalent. The
difference between the 2 Q-P-B options relates to the interval between the pentavalent vaccine
and the subsequent monovalent B vaccine. Notably, neither option is consistent with the
licensure for a 2-dose pentavalent or MenB series, and there is a lack of data regarding
immunogenicity with extended intervals between B doses. Option B adds Q -P-P to Option A.
That is , if an initial dose of pentavalent vaccine was given at age 16 years, a second dose could
be given 6 months later within the licensed indications to complete the meningococcal vaccine
series. Apart from this limited circumstance, pentavalent vaccine would not be used to replace MenB. Option C adds Q -Q-P-P and Q -Q-P-B to Option B. That is , in accepting PICO 3 fully, the
pentavalent vaccine could be given in lieu of MenB even after the MenACWY series has been
completed.
With this increased flexibility comes a higher cost and a lack of data on safety and immunogenicity of pentavalent vaccines in individuals primed with 2 doses of quadrivalent
vaccine. Notably, Q -Q-P-P and Q -Q-P-B options were not assessed through GRADE. In
22

 summary, all 3 options considered by the WG would permit the current standard of care of QQ
versus QQBB under shared clinical decision-making. Option A adds QPB, Option B adds QPP
on top of that and Option C adds QQPP and QQPB to Option B.
To summarize Options A, B, and C , Option B had the most favorable ratings overall. Option B is
best aligned with clinical trial data and proposed licensure and provides only 1 excess dose of
MenACWY. It also provides intermediate flexibility to stock 2 vaccines if using the pentavalent
vaccine for routine indications, assuming MenB at age 16 years. However, all options would
require stocking 3 vaccines for special situations , though 2 vaccines could be stocked
regardless if using only MenACWY and MenB. Option B also was the most cost-effective option
based on recent price updates from Pfizer . WG members felt there was lower potential for
insurance reimbursement issues .
For the balance of consequences for PICO 1, the pentavalent vaccine is an option for
MenACWY + MenB. The majority of WG members thought that desirable consequences
“probably ” or “clearly ” outweigh undesirable consequences in most settings. For PICO 1, the
majority of WG members favored recommending the intervention. For PICO 2, the pentavalent vaccine as an option for MenACWY only , the majority of WG members thought the undesirable
consequences “clearly ” or “probably ” outweigh the desirable consequences in most settings. For
PICO 2, the majority of WG members favored not recommending the intervention. For PICO 3, the pentavalent vaccine is an option for MenB. The WG did not reach a majority consensus on
the balance of consequences and were evenly split among the 3 options .
For the WG interpretation of PICO 3, an additional option was added because some WG
members favored Q -P-P only. WG members were divided regarding PICO 3. The majority of
WG members favored PICO 3 i n some form. However, a substantial minority of WG members
favored rejecting PICO 3 outright (Option A). The WG agreed to present Option B, Q -P-P, as a
compromise to the committee for further deliberation. The combined draft proposal for Option B
is as follows:
Pfizer’s MenABCWY vaccine may be used when both MenACWY and MenB are indicated at the same visit. *If MenABCWY is administered in this way, a second dose of MenABCWY may be administered 6 months later to complete the series.
The footnote reads :
*1) Healthy individuals aged 16– 23 years (routine schedule) when shared clinical
decision-making favors administration of MenB vaccination, 2) individuals aged 10 years
and older at increased risk of meningococcal disease (e.g., due to persistent
complement deficiencies, complement inhibitor use, or functional or anatomic asplenia)
due for both vaccines.
The WG also wanted to include the following remarks, which are not part of the proposal language:
Remarks:
• For Pfizer's pentavalent vaccine, data are not available regarding safety or
immunogenicity of dosing intervals exceeding 12 months.
• The licensed B component vaccines are not interchangeable by manufacturer.
Administration of a B component vaccine requires that subsequent B component vaccine (MenB or MenABCWY) doses be from the same manufacturer.
23

  • The minimum interval for Pfizer's MenABCWY vaccine is 6 months. Individuals at
increased risk for meningococcal disease who are recommended to receive additional doses of MenACWY and MenB, less than 6 months after a dose of pentavalent meningococcal vaccine should instead receive separate vaccines .
The rationale in favor of the combined draft proposal is that it aligns with clinical trial data and licensure; allows for fewer doses than QQBB; and provides flexibility with vaccine inventory,
including for clinics that prefer to sto ck 2 vaccines for routine indications, assuming MenB at age
16 years. In addition, stocking fewer vaccines may increase equity (e.g., if under -resourced
clinics are less likely to st ock 3 vaccines). This is the most cost-effective option based on the
recent price update from P fizer. The rational against the combined draft proposal was that it has
unnecessary ACWY antigen exposure for the second pentavalent dose in the routine schedule when only MenB is indicated. In addition, there is as much flexibility for providers as in Option 3.
General considerations against all options include the potential to incentivize MenB at age 16
years with waning immunity by peak risk for some patients, such as those entering college or
the military . There also is uncertainty regarding the cost estimates . If using the pentavalent
vaccine, it will be necessary to sto ck 3 vaccines to cover all indications (routine schedule +
special situations) , which may be challenging for some vaccine providers.
Discussion Points
Dr. Talbot requested clarification about how clinical decision-making would work if someone
receives B through shared clinical decision-making then receives Q as the second dose, whether they would have to have shared clinical decision-making of Q versus P and then w ould
have to have shared clinical decision-making if they decide to receive B, or if they had already decided to do B if they did P. If it is shared clinical decision- making, it seems that all 3 vaccines
would need to be stocked (Q, P, and B ).
Dr. Poehling said that when she would embark on this conversation would be at the time of the second dose to indicate that there are 2 types, ACWY and B, and then go through which ones
would be done. If B will be included, she would explain that it could be done separately or all
together . It would be shared clinical decision-making for B regardless. A very small clinic might
elect to carry B in the pentavalent vaccine and perhaps refer those who want only B to a health
department. A larger organization probably would opt to carry all 3.
Dr. Long emphasized that the ACIP did not decide to make this combination vaccine.
Meningococcal disease is the only thing putting them together, and it would be easy to advertise
this as the full meningococcal panel. But meningococcal diseases, as uncommon as they are, are also extremely different in that secondary cases occur very quickly with C, W, and Y and it is
difficult to recognize if there even is an outbreak of B because it may be 2 cases over 3 months
or 3 cases over 18 months. It is a vaccine that is much better targeted for outbreak use because
it also has a very short period for which it provides terrific efficacy. Another difficulty is that the
existing schedule already is not quite right because the prevention of B starts later than the
second dose of CWY. It is difficult for the ACIP to come up with much that would be good
utilization of funds and resources if they try to put these together ever. She is very cognizant
that not one more antigen should be given than needed. A lthough this has been done with
combination vaccines for small children when they are receiving so many vaccines concurrently,
that is not the case here. She inquired about whether there could be an amendment prior to the
proposed vote to not vote.
24

  Dr. Kotton said that as an adult provider, she did not want to comment on the pediatric issues,
which are complicated. However, she administers many doses of meningococcal vaccine—
especially to people who have had splenectomies. She remains astounded at the number of
Americans who have had splenectomies who are under -vaccinated. In her experience, she
would estimate that well over 80% of people who have had splenectomies are poorly
vaccinated. It would be good to offer them an easy option. Furthermore, she sees people who
are going to become immunocompromised, who are thinking about starting e culizumab and
other similar drugs that greatly increase the risk of meningococcal disease. Although she is
excited about the opportunity to have a pentavalent vaccine because she often is giving so
many vaccines in clinic that it becomes onerous to the patient. When they have to have 2 different vaccines or when she is sending them to a commercial pharmacy and they have to get 2 different vaccines, it is very complicated. The fact that she would need to separate the
pentavalent by at least 6 months, usually my patients do not have 6 months to wait, and they
may not return for a vaccine. This is really onerous and problematic and very messy.
Vaccination for Americans needs a simpler process. Being a clinician deep in the trenches is
really challenging these days and they need to provide simplicity.
Dr. Loehr asked if the ACIP voted/made a recommendation on the pentavalent vaccine during
this meeting how that would affect future pentavalent vaccines in terms of whether there would
be a new vote or if this vote would apply to new vaccines.
Dr. Wharton indicated that it would depend on the characteristics of future pentavalent vaccines.
If the licensed indications are close to the same as this product, it probably could apply to a future vaccine. If there are meaningful differences, it would be brought back to the committee.
As a member of the Meningitis WG, he has been a strong proponent for the Q -P-B option.
When this all started, he was thinking of it as an opportunity to give one less vaccine. However,
he did not want to give extra antigens to people. Someone pointed out that some clinics might
stock only a pentavalent vaccine, which had not occurred to him. There is no way he wants to
give a pentavalent vaccine to an 11- year-old because B is not necessary at that time, which he
thought was why many of the WG members voted against PICO 2. He likes the concept of not
giving extra antigens and was trying to make a decision on how to vote, because that is a
separate issue. The cost -effectiveness that was an issue is no longer an issue because Pfizer
changed the price. He said he was disgruntled by the way Pfizer changed the price and the way
they framed it, but that is the way it is and we have to accept reality as it is. Some parents ask
him if he can use a different schedule for their children’s vaccines. He tells them that they can,
but he recommends the schedule as it is because those are the data they have. He realized that if he votes for Q-P-B, that is off-label and is not the schedule the way it was studied. That is a
significant issue for him. He wanted to make sure they always have shared clinical decision-making for B. He is probably going to need to stock 3 vaccines anyway, because he is going to
have some people who do not want B and he will need Q. It is just going to be complicated, so he likely would vote for the Q-P-B option, but was less starkly in favor of that than he was over
the last 2 to 3 months.
Dr. Daley said he was struggling and thought that the vaccines were not well -matched. While he
is grateful that there are vaccines to prevent meningococcal disease given its severity, now
there is a set of vaccines and a schedule that are not well -matched with the epidemiology . In
terms of Dr. Talbot’s question earlier about not making a recommendation during this meeting, he is generally not in favor of “kicking the can down the road.” Given that it is a licensed vaccine, the ACIP should provide some guidance. However, it is problematic that they were re-
evaluating the entire schedule as they were voting and there was the added uncertainty about
25

  the cost-effectiveness. He said he also thought that sometimes , there is a benefit of having a
monovalent MenB vaccine, because that provides flexibility to time the dose when it is most
effective for the circumstance. Dr. Long said it beautifully. In outbreaks , it is short-term
protection. It is important for the ACIP always to think about unintended negative
consequences . If there is a lot less monovalent MenB, that removes a tool from the toolbox.
While he was still struggling, he said he was in favor or either not voting on a pentavalent use
during this meeting, recogniz ing that would be problematic for the ACIP and the manufacturer
who cannot plan as well, or making narrow recommendations. By “narrow” he explained that he
would favor PICO 1, but with narrow recommendations because they would revisit this in the
context of an overall conversation about how to best tailor the schedule for the epidemiology
and resource use.
Dr. Lee said that at this point, she wanted to express the areas where she felt most strongly
about this particular decision. She agreed that the benefit-risk balance in minimizing
unnecessary exposure to antigens was an important one and that the reason this was
complicated was due to the way the current schedule is set up. Recognizing that their
colleagues had some work to do and thinking about how the post-COVID epidemiology had
perhaps changed the benefit-risk balance, she also recognized the need for rigorous evaluation.
She favored the Q-P-B option at this point. It’s a choice of a product people can have. Her
thinking was that a pediatrician could stock QQ with shared clinical decision-making for QQ and
BB as the options. But if people have a preference, or they want to have a product choice, they could decide to replace the QB combination with a pentavalent. Having said this, she realized
that it sounded very confusing and challenging, especially for frontline clinicians. She would
frame this not as the recommendation, but rather as a choice for people to make, and they
could stick with the original schedule. As Dr. Kotton mentioned, there are situations in which
transplant patients are being vaccinated who need protection for both. In those instances, she
could imagine giving PP in those instances as an option for those high-risk individuals. If they
assume that the current schedule remains with an option for people to choose to receive QPB
as an alternative, recognizing the complexities of that, it would give the ACIP the opportunity to
move toward a PP schedule in the future as they start to think about the ages. But one thing I did want to clarify and ask, actually two things. Referring to the special situations listed on Slide 2, there is some dissonance in terms of the risk -based categories for ACWY and B. She asked
whether the WG could make that simple because the inconsistency makes it challenging.
With regard to the dissonance between the MenACWY and MenB recommendations , Dr.
McNamara pointed out that these are longstanding recommendations that have reasons behind
them. The epidemiology showed that among people with HIV infection in the US , there was a
predominance of CWY disease and not B disease. Similarly, travel to hyperendemic areas is largely about the African Meningitis Belt where there is no serogroup B. They can look at this in
reviewing the schedule over the next year to determine if there are opportunities to better
harmonize, but probably could not make changes during this meeting.
Dr. Poehling added that the reason first year college students and military recruits are not
checked on the special situations table is because the MenB column is ≥10 years of age.
Dr. McNamara noted that the recommendations for first year college students and military
recruits, the recommendations are for people who did not receive MenACWY vaccines already,
so they are not current for ACWY per their routine adolescence schedule . There is a shared
clinical decision-making recommendation for serogroup B in the adolescent schedule, so
someone who has not received those is not considered not up-to-date.
26

    Dr. Poehling thanked everyone for wrestling with this , which was not easy and the conversation
is appreciated. If the ACIP voted for the QPP, which was included in PICO 3, that has an extra
ACWY dose administration. That has occurred with other combination vaccines, so she wanted
to put it in the context of the current vaccine schedule.
Dr. Sanchez emphasized that meningococcal recommendations are confusing and always have
been, at least to him. He understood the concern regarding minimizing antigen exposure, and they have heard about combination vaccines that result in exposure to more than 3 doses, such
as Hepatitis B and with the tetanus recommendation in which one can receive acellular
pertussis and diphtheria rather than just a tetanus monovalent. This is known to be safe, so he
was not as concerned about this . The biggest issue to him was the that if the pentavalent
vaccine was recommended for meningococcal B, that also would expose adolescents 11 to 12
years of age to antigens that are not needed until later. It seemed reasonable to offer the
pentavalent vaccine if they also are recommended to receive the meningococcal B component
for college entry. Many states require that as well, so it seemed like a reasonable option in
certain circumstances versus universally. It certainly would reduce the number of doses of
injections given. He asked what data are available on simultaneous administration of other vaccines with the pentavalent meningococcal vaccine.
Dr. Collins indicated that direct data are not available on concomitant administration of the
pentavalent vaccine with other vaccines. They best they could do was to look at Nimenrix, which
is the MenACWY component in the pentavalent vaccine. Information from the package insert
4
states that, “Safety and immunogenicity of Nimenrix was evaluated when sequentially
administered or co-administered with a DTaP/IPV/Hib/HepB  vaccine in the second year of life.
The administration of Nimenrix 1 month after the DTaP /IPV/ Hib/HepB vaccine resulted in lower
MenA, MenC, and MenW135 Geometric Mean Titers (GMTs) as measured with a serum
bactericidal assay using rabbit complement (rSBA) . The clinical relevance of this observation is
unknown, since at least 99.4% of subjects (N=178) had rSBA titer s of ≥8 for each group (A, C,
W-135, and Y) .” Guidance is provided in the package insert stating that “Whenever possible,
Nimenrix and a tetanus toxoid (TT) containing vaccines , such as DTaP/IPV/Hib/HepB vaccine,
should be co-administered or Nimenrix should be administered at least 1 month before the TT-containing vaccine. One month after co-administration with a combined tetanus toxoid, reduced
diphtheria toxoid and acellular pertussis vaccine, there were lower GMCs observed for each of the pertussis antigens and more than 98% of subjects and antibody levels above the thresholds.  Again, the clinical relevance of this observation is unknown. There are no data with the
pneumococcal conjugate vaccine.
Dr. McNamara noted that the current licensed meningococcal ACWY vaccines in the US also
have some similar interference with the pertussis -containing vaccines. Similarly , the clinical
relevance of those observations is unknown and so there have not been recommendations to
date about not providing those vaccines concomitantly.
Dr. Talbot said she greatly appreciates the need for the ACIP to review FDA -approved vaccines
quickly for vaccines that are coming to market. In the cases of RSV and COVID, that was
critical. However, this has diverted the ACIP away from reviewing the meningococcal guidelines
first and has been a distraction. In that vein, and at the risk of having everyone on the
Meningococcal WG angry with her, she asked if it would be possible to accelerate the planned
review of the guidelines so that the ACIP could vote in June 2024 instead of later.
4 https://labeling.pfizer.com/ShowLabeling.aspx?id=12217
27

   Dr. McNamara indicated that they are still seeking a permanent replacement to serve as the
Meningococcal WG lead, so she could not comment on acceleration. This has been considered
extensively and there is a lot of work to do in terms of reviewing the adolescent schedule.
Extended interval data for pentavalent vaccines administered ≥3 years apart is anticipated to
become available over the next year, though an exact date is unknown. This information is
important in terms of considering different vaccine schedule options. Speaking for herself, she
would be hesitant to change the schedule in advance of having those data because she would not want to change the schedule twice.
Dr. Lee emphasized that she thought the ACIP needed to vote during this meeting, though
members were free to vote not to make a recommendation.
Dr. Loehr recognized that it was nice to have an option for patients and to have a safe and
effective vaccine option, and thanked the manufacturer for presenting this and making it
available. He asked Dr. Wharton to inform the ACIP on Robert’ s Rules of O rder in terms of
whether it would be better to make a motion for a vote and then have someone try to table it or to make a motion to table it first.
Dr. Wharton pointed out that they could not table a vote that had not been moved. If a
committee member want ed to move this toward a vote during this meeting, they should make a
motion to that effect. If the motion was seconded and someone wants to amend the recommendation, they could make that motion. Then the debate would be on the amendment rather than the original motion.
Dr. Loehr made a motion in favor of the Combined Draft Proposal for Option B for the
ACIP to accept the language as proposed in Dr. Collins’ presentation Slide 38. Dr. Sanchez seconded the motion for the ACIP to adopt the recommendation language as
proposed.
Dr. Collins read the language for the record:
Pfizer’s MenABCWY vaccine may be used when both MenACWY and MenB are
indicated at the same visit. *If MenABCWY is administered in this way, a second dose of MenABCWY may be administered 6 months later to complete the series.
The footnote reads :
*1) Healthy individuals aged 16– 23 years (routine schedule) when shared clinical
decision-making favors administration of MenB vaccination, 2) individuals aged 10 years
and older at increased risk of meningococcal disease (e.g., due to persistent
complement deficiencies, complement inhibitor use, or functional or anatomic asplenia)
due for both vaccines.
Dr. Talbot made a motion to make an amendment to postpone the vote for the pentavalent meningococcal disease vaccine until after re-evaluation of the currentmeningococcal guidelines as there are currently adequate vaccines to cover all of these
pathogens, and to reduce the complexity and the number of vaccines that need to be in a
provider’s office. Dr. Long seconded the motion.
28

 Dr. Long pointed out that the ACIP has a long history of difficulty in rescinding
recommendations, decreasing antigens , or decreasing vaccines. Perhaps looking at the entire
schedule, they may decide that these vaccines , CWY versus B, should be separated by age
group and indication. They already would change the architectural plan if they approve the
combination pentavalent vaccine. Then they would have to convey to people that there is something currently licensed and recommended in an odd way, but recommended, that would
be moot because most people would not receive these 2 vaccines at the same age or
indication. If a bigger change is planned, the incremental change should not be made first. She
also pointed out that the proposed language would not be the narrowest indication for use of the pentavalent vaccine. The narrowest indication would be to use it only when both are
recommended and that would just be for the second dose of CYW.
Ms. Arthur (BIO) asked how long the delay would be before there would be a vote if the
amendment were to pass. She understood that the WG is considering some data and important
issues pertaining to the adolescent schedule, which could mean no vote for this product for 12
to 15 months or more .
Dr. McNamara noted that if the intent was to table the vote on this question until after the new
votes on the adolescent meningococcal schedule, CDC discussed with the WG having that vote
in February of 2025. Her default assumption would be that the pentavalent vote would occur at
that time as well. Obviously, nothing is set in stone. However, reassessing the schedule will take a significant amount of time.
Dr. Brooks said he did not feel that the ACIP could delay the vote and spoke against the
amendment. He recognized that the ACIP did not ask the manufacturer to make the vaccine as
Dr. Long pointed out, but they did, and he is grateful for it as Dr. Loehr said. The WG was
strongly in favor of PICO 1 and strongly against PICO 2. If there were concerns or questions,
the simple thing to do would be to vote against PICO 3 and choose Option A, PICO 1 (QPB) if
both are needed. That would be an incremental change that would not commit the ACIP to
anything they did not want. He agreed that the ACIP has a history of making tough decisions ,
and this has grown tougher with every meeting.
Dr. Sanchez said he certainly understood that and wanted a revisit of the meningococcal
schedule, at least in children. Knowing that will be in the distance and there is an FDA -approved
vaccine is available, there are circumstances in which children will receive both vaccines, Q and
B, it made sense to make it available under certain circumstances and under certain
recommendations, rather than tabling it for some future change. He suggested making the
recommendations without adding anything more to an already complicated schedule. Dr. Daley pointed out that Dr. Brooks was talking about the option on the screen, but his
understanding is if we are in favor of what is on the screen, ACIP would need to vote down the
amendment and the first proposal both, and then someone would need to make a new motion for this.
Dr. Lee agreed with Drs. Sanchez and Brooks that the ACIP needed to make a decision, and
that deferring that decision would not be helpful for frontline pediatricians and family
practitioners.
Dr. Lee spoke in favor of Option A.
29

 Vaccines for Children (VFC) Resolution
Dr. Jeanne Santoli (CDC/NCIRD) indicated that they prepared for the multiple options, which
would be reflected in her presentation of the VFC Resolution. She explained that the purpose of
this resolution was to update the resolution to add a new component to the VFC Resolution to
reflect a newly available combination meningococcal vaccine that can be used to prevent meningococcal disease attributable to serogroups A ,C,W,Y and B, and to make minor updates
to the existing components of the resolution (MenACWY component and MenB component).
For the MenACWY component, there are no proposed changes to the eligible groups. For the recommended vaccination schedule and intervals, there are 3 changes. The first would be to remove Menactra, which is no longer available as an option. The s econd would be to remove a
footnote that was used to add Menveo 1-vial to the VFC resolution when that vaccine was
licensed as an alternative product to the products that already were part of the resolution. No
changes were proposed for the recommended schedule, dosages, or contraindications and
precautions. For the meningococcal B component, the change to the eligible groups was to reference shared clinical decision-making because it was not referenced initially, and it is
referenced in the new proposed component. For consistency, that was added to the second
bullet here under the eligible groups. A statement was added to the recommended vaccination
schedule and intervals table that was missing from the original resolution to add a footnote
making clear that MenB vaccines are not interchangeable by manufacturer. No changes would
be made to the recommended dosages or contraindications and precautions.
Pertaining to the upcoming vote on the combined pentavalent serogroup A,C,W,Y, and B
vaccine, Dr. Santoli reviewed the eligible groups, recommended vaccination schedules and
intervals for each Option A, Option B, and Option C that mirrored what the ACIP had been
discussing. For Option A, there would not be a change to the eligible groups but there is a change in the second dose for children who are not at increased risk. This clearly indicates a monovalent, which was not the case for Option B. Otherwise, Options A and B were the same in
the resolution. Option C included additional changes to acknowledge the use of the combination
vaccine when MenB alone is recommended. That also was reflected in the recommended vaccination schedule and intervals.
No changes were made to the standard statement indicating that when there is a published
recommendation, the information is incorporated by reference. Any c ontraindications and
precautions would be added prior to the VFC resolution being brought forward for a vote.
Discussion Points Recognizing that the final VFC vote would depend upon the final ACIP recommendation
vote, Dr. Loehr moved to accept the VFC language as presented. Dr. Daley seconded the
motion.
Dr. Long said that after listening to her colleagues and understanding that there was not
support for tabling the pentavalent vote, she wanted to withdraw her seconding on the
motion to table the vote. With no other seconds, this amendment did not pass.
Dr. Wharton clarified that with the second withdrawn pertaining to the amendment, there now was only one motion on the table for Option B as written. The amendment does not pass and ACIP returns to the original motion put forth by Dr. Loehr, which was Option B. Is any other discussion needed at this time?
30

   Dr. Loehr asked if any colleagues wanted to do the amendment for Option A, now would be the time to do that.
Dr. Brooks asked if we would have to vote this motion down and have that option as a second
motion.
Dr. Lee said there are 2 options, Option B (the initial motion) and if anyone wanted to request an
amendment to the motion, essentially going to Option A, that is acceptable. Or you could vote
down this one and have another vote.For the sake of clarity, it would be easier to have all potential motions/votes on the table before moving to the voting section. She requested that
Option B and Option A be displayed.
Option B and then Option A were displayed.
Dr. Lee asked if anyone wished to make an amendment to vote for Option A. Dr. Daley made an amended motion to adopt the language for Option A as written. Dr.
Brooks seconded the motion.
Dr. Lee clarified that Option A, the amendment, would be voted upon first. If that did not pass,
they would move to Option B.
Dr. Talbot pointed out that many of her colleagues were concerned about postponing this vote
because physicians will be asking how to use this vaccine. While that is a legitimate concern,
the reality is that insurance will not cover the vaccine if the vote is postponed. It was not a question of how to use the vaccine, but whether patients would have to pay out-of-pocket. In terms of pediatricians calling with questions, there are 3 licensed vaccines that already are currently covered by insurance and the VFC. She emphasized that she did not think the ACIP
should make judgments based on other people’ s questions or how fast a pharmaceutical
company wants to push a vaccine to market and instead thought that the ACIP should make
decisions based on what is the simplest and provides the best care for their patients.
As a reminder, public comment was presented prior to the votes. However, the votes were
combined in this proceedings document with their respective sessions for the purpose of
continuity.
Vote: Meningococcal Vaccine
Dr. Jennifer Collins (CDC/NCIRD) recapped the votes on the table for Options A and B, which
were as follows:
Option A (Amended Motion)
Pfizer’s MenABCWY vaccine may be used when both MenACWY and MenB are
indicated at the same visit.*
Footnote
*1) Healthy individuals aged 16–23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccination, 2) individuals aged 10 years and older at increased risk of meningococcal disease (e.g., due to persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia) due for both vaccines.
Option B (Initial Motion; only voted on if the amendment fails)
31

  Pfizer’s MenABCWY vaccine may be used when both MenACWY and MenB are indicated at the same visit. *If MenABCWY is administered in this way, a second dose of
MenABCWY may be administered 6 months later to complete the series.
Footnotes
*1) Healthy individuals aged 16–23 years (routine schedule) when shared clinical decision-making favors administration of
MenB vaccination, 2) individuals aged 10 years and older at increased risk of meningococcal disease (e.g., due to persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia) due for both vaccines.
Dr. Lee reminded everyone that the second for the motion to table the vote until a future time
did not pass, given that the second was rescinded and no other seconds were made. There was then a motion and a second to amend the vote on the floor to vote on Option A, which would be voted upon first. If that did not pass, they would move to Option B. If it did pass, there would not
be a vote on Option B. She asked ACIP members to put their cameras on.
Motion/Vote #1: Option A Meningococcal Recommendation
Dr. Daley made an amended motion to adopt the language for Option A as written, which Dr.
Brooks seconded. No COIs were declared. The motion carried with 10 affirmative votes, 4
negative votes, and 0 abstentions. The disposition of the vote was as follows:
10 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Long, Sanchez
4 Opposed: Loehr, McNally, Poehling, Talbot
0 Abstained: N/A
Vote: Meningococcal VFC Resolution
Dr. Jeanne Santoli (CDC/NCIRD) recapped the VFC vote for meningococcal vaccines, which
will reflect that the ACIP voted to approve Option A that will be reflected in the VFC Resolution
accordingly.
Motion/Vote #1: Meningococcal VFC Resolution
Dr. Loehr moved to accept the VFC language as presented, which Daley seconded. No COIs
were declared. The motion carried with 14 affirmative votes, 0 negative votes, and 0
abstentions. The disposition of the vote was as follows:
14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally,
Poehling, Sanchez, Talbot
0 Opposed: N/A
0 Abstained: N/A
32

   Discussion Points
Dr. Poeling thanked everyone for the robust discussion about meningococcal vaccines. There
has been tremendous benefit from the vaccines that are being administered, and there is a lot
more to learn. She voted “no” to Option A because she wanted a broader recommendation, emphasizing that she r espected the votes of her colleagues and expected there would be many
more conversations to come about meningococcal vaccine.
Dr. Daley pointed out that one of the overarching goals of the entire program is to maximize
prevention of vaccine-preventable disease, morbidity, and mortality. That is fundamental in the
context of resource constraints and other constraints. Therefore, he would expect that the work
of the Meningococcal WG would include evaluation of a MenB prevention strategy. The problem
was that this was not the direct questions under consideration during this session, so he wanted
to highlight that distinction. In fact, conflating those two made it harder to make a decision. He
thought they should foc us on the decision at hand, recognizing that there are compelling
reasons to re-evaluate the current strategy for Men B, which is rare but severe.
Ms. McNally emphasized that while she favor s MenB vaccination and fewer injections , she also
was hoping for a broader recommendation.
MPOX VACCINES
Introduction
Pablo Sanchez, MD (ACIP, WG Chair) provide an introduction and overview of the Mpox
session , reminding everyone that the global Mpox outbreak occurred in 2022 with the first case
identified in the United Kingdom (UK) in May 2022. It primarily affected gay, bisexual , and other
men who have sex with men (MSM). It was associated with person-to-person spread via close
skin-to-skin contact, including sex. D eaths have occurred, primarily among persons with severe
immunocompromise from advanced HIV. US case counts and deaths comprised a third of the
cases and deaths, with over 30,000 cases with 54 deaths. In terms of the current global cases ,
during September 2023, the US has reported 30 to 99 cases. There are large number s of
cases in Southeast Asia and Indonesia during this same time.
As a reminder, the JYNNEOS vaccine is comprised of a replication-deficient vaccinia virus ,
which is a live virus that is replication-deficient. It is administered subcutaneously via 2 vaccine
doses administered 28 days apart. Its effectiveness was assessed by comparing immunologic
response to that for ACAM2000. It was licensed for prevention of both smallpox and Mpox, and
it is currently recommended for persons with HIV and other immuno compromising conditions .
JYNNEOS vaccine is licensed for persons ≥ 18 years of age. There is a current NIH trial
underway to evaluate the safety and immunogenicity for persons 12─ 17 years of age.
The outbreak recommendations were previously discussed during the February and June 2023
ACIP meetings . In June 2023, the ACIP voted to recommend the 2-dose JYNNEOS vaccine
series for persons ≥ 18 years of age at risk of Mpox during an Mpox outbreak. P ublic health
authorities determine whether there is an M pox outbreak. A single case may be considered an
Mpox outbreak at the discretion of the public health authorities. The outbreak recommendations
were intended for any US Mpox outbreak regardless of whether it is associated with male-to-
male sexual contact. The clinical guidance, including use of the vaccine in children during
33

 outbreaks , were discussed as well. The national Mpox vaccination strategy for pre-exposure
vaccination during the current outbreak includes the following individuals :5
• Gay, bisexual, and other MSM, transgender or non-binary people (including
adolescents who fall into the forementioned categories) who in the past 6 months
have had:
− New diagnosis of ≥1 sexually transmitted disease
− More than one sex partner
• People with the following in the last 6 months :
− Sex at a commercial sex venue
− Sex in association with large public events in geographic areas where Mpox
transmission is occurring
• Sexual partners of people with the above risks
• People who anticipate experiencing above risks
• People with HIV or other causes of immunosuppression who have had recent or
anticipate potential Mpox exposure
The World Health Organization (WHO) is embarking on the development of an elimination
program of human-to-human transmission of Mpox. Certainly , additional resources and data are
needed. Immunization will be one component of the strategy for worldwide elimination of Mpox
disease. Elimination is a complex issue that has not been addressed by the WG . However, a
recommendation that persons at risk for M pox during the ongoing outbreak receiving the
vaccines, if they have not already, may support any upcoming strategy from the WHO with
respect to future elimination of M pox. Dr. Sanchez indicated that the interim routine
recommendation to be proposed for a vote during this session would read as follows:
ACIP recommends vaccination* with the 2-dose† JYNNEOS vaccine series for persons
aged 18 years and older at risk for Mpox§
*Interim recommendation that ACIP will revisit in 2-3 years
†Dose 2 administered 28 days after dose 1
§Persons at risk:
• Gay, bisexual, and other men who have sex with men, transgender or nonbinary people 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
The potential implications of an interim routine recommendation are that it would increase
vaccine coverage and prevent or minimize future outbreaks, and remove some stigma and
facilitate one-to-one consultation with clinicians during their appointments for vaccination. It also
heralds the potential commercialization of the JYNNEOS vaccine. The product sponsor, Bavarian Nordic, has indicated that they will attempt to commercialize the vaccine if it is on a
routine schedule. This would transition the vaccine from US government stockpiles, which were intended for smallpox preparedness , to the commercial sector.
5 https://www.cdc.gov/poxvirus/monkeypox/interim-considerations/overview.htm
34

  Regarding the tentative timeline for ACIP discussions and votes, this meeting would result in
interim routine recommendations if the ACIP adopts the recommendation and clinical guidance.
Publication is planned for 2 Morbidity and Mortality Weekly Reports (MMWRs) in 2024,
including: 1) Use of the JYNNEOS vaccine during M pox outbreaks; and 2) Use of the
JYNNEOS vaccine among persons at risk during the ongoing Mpox outbreak. Potentially in
2024, the ACIP would consider the results from an ongoing NIH trial on the use of the JYNNEOS vaccine in adolescents 12─ 17 years of age. The epidemiology, cost-effectiveness
analysis, and other data would be reviewed in 2 to 3 years to determine whether a routine
recommendation should be continued.
Updates about US Mpox Epidemiology, Vaccine Safety, and Vaccine Effectiveness
Faisal Syed Minhaj, PharmD, MPH, DABAT (CDC/NCEZID) provided updates on US
epidemiology, vaccine safety, and vaccine effectiveness (VE). Beginning with situational awareness and updates in terms of Mpox case counts from the beginning of the outbreak in
May 2022 through September 28, 2023,
6 the peak of M pox cases occurred during August 2022
and cases have decreased substantially in 2023. Taking a closer look at the numbers in 2023,
the case counts from the beginning of the year to September 28, 2023 did not reach zero at any
point. During the month of January, the 7-day average case range was generally between 5 and
7 cases per day. Cases decreased in February down to 1 to 3 cases per day. However, they
rose again in the summer months up to 5 cases per day. From July through now, there is still an
average of one to four cases per day. Cases have not been consistently below this level,
highlighting that Mpox has not been eliminated from the U S. Looking at the cases in 2023
geographically, cases are occurring across the US in different jurisdictions. C ases are spread
out and many are not linked to other known cases, which suggests continued community
transmission or potential underdiagnosis. D uring the height of the outbreak in Summer 2022
when clinician awareness was high and vaccine campaigns were occurring, the rate of undiagnosed Mpox was likely low at around 1% in the MSM population. Seeing unlinked cases
currently across jurisdictions suggests additional ongoing transmission.
Cases have been seen in patients following vaccination. This has been reported since the
outbreak started, including some clusters. However, it is relatively rare in comparison to the total
case counts. Importantly, most patients with infection following vaccination have mild illness .
Data from a recently published manuscript on infections following vaccination
7 show that the
median number of lesions in these patients was 2, with an interquartile range of 1 to 5.
Additionally, only 2 out of 30 patients received tecovirimat and few were hospitalized,
suggesting that illness was mild following vaccination.
Reinfection of Mpox is rare and was not well -reported until the current outbreak. Potential
reinfection cases have been published in the literature, but only a few with convincing evidence
of true reinfection. In a recently published case series ,8 the authors found a total of 8 probable
cases of reinfection. Reinfection appears to be mild with a lower lesion count and duration of
rash. CDC is aware of less than 10 cases of probable reinfection, which makes up less than
0.001% of cases.
6 https://www.cdc.gov/poxvirus/mpox/response/2022/mpx-trends.html
7 Hazra A. Lancet Infect Dis. 2023 Sep 4:S1473-3099(23)00492-9
8 Hazra A. Lancet Infect Dis. 2023 Sep 4:S1473-3099(23)00492-9
35

   CDC’ s mpox c linical consult service was created early in the outbreak to discuss any Mpox
case s and transitioned to be a resource for treatment and guidance on managing severe M pox
cases. The consultation service is the only way to access most medical countermeasures
available for severe M pox. These consultations include some new cases, but many are
repeated consultations on infections that began months ago and require numerous courses of
available medical countermeasures. From the beginning of the outbreak to now , 54 people have
died in the US, with another 2 in September 2023. As CDC published in 2022,9 people with
severe Mpox and deaths share the same equity disparities seen between cases and
vaccination. Black persons make up the majority of severe cases . Most severe cases often have
advanced HIV or AIDS, are not on antiretrovirals at diagnosis, are not linked to care, many are
experiencing homelessness , and importantly are not vaccinated with JYNNEOS.
In terms of demographics, the gender and age distributions of M pox cases have not changed
since the June 2023 ACIP presentation. Most cases are among cisgendered males , highlighting
the population for which JYNNEOS vaccination is recommended. The race and ethnicity of reported cases also remains similar to what was reported in June. Early in the outbreak, greater
than 40% of cases were detected in White persons, but during the peak of 2022, Black and
Hispanic persons were most affected. Recently , there have been cases across different racial
and ethnic groups, but with large proportions of cases among Black and Hispanic persons
throughout the outbreak ;
10 Achieving vaccine equity is needed to address this disparity.
Globally, there is a different trend of cases than in North America. Between April through
September 2023, there have been large increases in Southeast Asian and Western Pacific
regions. Over the past month, the European region also had one of its largest relative increases
from August to September. Many recent increases were from countries in East and Southeast
Asia based on detections from September 4 through September 24, 2023.11 These are not the
only countries in this region experiencing an increase in cases. Earlier in the week, there were
news reports of new cases detected in Vietnam and Indonesia. When examining cases globally,
it is important to recognize that robust M pox surveillance systems and vaccine implementation
programs seldom exist outside of Europe, Canada, and the U S.
Vaccine uptake slowed dramatically following the peak of the outbreak in July through
September 2022. Since the beginning of the outbreak in May 2022, first dose vaccine coverage
is 38.8% and second dose coverage is 24.3% among the estimated at-risk people who are
eligible for vaccination. Those at risk for M pox are defined as HIV-positive and pre- exposure
prophylaxis ( PrEP)-eligible individuals totaling an estimated 2 million persons in the US. An
incredible effort was put forth into achieving over 1.3 million doses administered. However, there is room for improvement. Ninety -three percent of doses were administered in 2022, and
although there was a shift from first to second doses in 2023, second dose coverage remains below 1 in 4 and 37 of 54 jurisdictions are still below these national coverage estimates,
emphasizing the work needed to get at-risk people primary vaccination. Moving forward, a
younger unvaccinated population also will age into those eligible for primary vaccination.
There also has been a shift in vaccine administration sites from public health clinics to medical
centers. Public health providers administered 40% of all vaccines through March 2023. Medical
care providers administered an increasing proportion of vaccines since the start of the outbreak, and pharmacies consistently provided 3% to 4% of all vaccines. Looking closer at the types of
medical center providers giving vaccine, there were statistically significant increases in vaccines
9 https://www.cdc.gov/mmwr/volumes/71/wr/mm7144e1.htm
10 https://www.cdc.gov/poxvirus/mpox/response/2022/demographics.html
11 https://worldhealthorg.shinyapps.io/mpx_global/
36

  provided by primary care offices, F ederally Qualifying Health Centers (FHQCs) , and other
health centers.
Now to discuss a few models12 relate d to vaccination in the current outbreak and why
vaccination is an important strategy to prevent ongoing cases. Based on the results from a
model of M pox transmission in Washington, DC in which the model estimated cases averted by
behavioral adaptation, vaccination, or both interventions , surveys indicate that individuals
reduced the number of sexual partners in response to M pox. This scenario does not include
vaccine administration. The model estimates that behavioral adaptation alone could have quickly flattened the curve, but not ended the outbreak within 1 year. Based on vaccine
administration records in DC, not including behavioral adaptation, the model indicates that
vaccination would have taken longer to have an effect than behavioral adaptation, but would
have ended the outbreak within a year. Based on the model estimates of prevalent infections
with vaccination and behavioral adaptation combined, the model estimate d that combined,
these 2 interventions averted 80% of potential Mpox cases in DC , with behavioral adaptations
being key to averting cases early on and vaccination being key to ending the outbreak. Similar
results also were found in models in other cities.
Models not only estimate that vaccination is key to ending the M pox outbreak, but also that
vaccination is key to preventing Mpox resurgence.
13 Later in the outbreak in DC, the model
estimated that nearly the entire high- risk population of MSM who engages in 1-time sexual
partnerships gained full or partial immunity through vaccination or through acquiring and
recovering from Mpox making resurgence in DC unlikely. However, over time, population level
immunity will decrease due to population turnover. Further, most US jurisdictions had a lower vaccine coverage than DC , potentially leaving them vulnerable to resurgence. For the purposes
of this model, either 1- or 2-dose vaccination was used. It is known from VE data that 2 doses is
greater protection. In this model, they defined a resurgent outbreak as continuous community
transmission for at least 3 months, the risk of recurrence decreases linearly as population level
immunity increases. While the probability of recurrence decreases linearly with population level immunity, the size of potential outbreaks has a more complex relationship with population level
immunity. The model estimates that resurgent outbreaks will be very small if the population level
immunity is greater than 50%. Currently, only 7 jurisdictions are above 50% with at least 1 dose
of JYNNEOS coverage among the high-risk population.
In terms of the VE and safety updates. These data were presented during previous ACIP
meetings. To summarizes the available VE data from 3 separate studies in the US (1 from Epic
Cosmos, 1 from a multi -jurisdictional case-control, and 1 from New York State), 1-dose VE
ranged from 36% to 75%. VE ranged for from 66% to 89% for 2-dose vaccination. Consistently
across the studies, VE for 2-dose vaccination was higher than 1 dose, emphasizing the
importance of finishing the 2-dose series.
To update VE estimates from the multi -jurisdictional case-control study that was performed in 12
US jurisdictions and initially presented during the February 2023 ACIP meeting. The population
is MSM 18-49 years of age and the time period is August 19, 2022 through September 27,
2023. Cases were identified from a jurisdiction’ s list of Mpox cases, while controls were
identified from healthcare settings providing HIV P rEP or sexually transmitted infection ( STI)
clinics. VE was adjusted for age, race, ethnicity , and immunocompromising conditions. It was
12 ttps://www.medrxiv.org/content/10.1101/2023.02.10.23285772v1.full.pdf Lines  and shaded regions reflect median and
interquartile range from 120 simul
13 Pollock ED. MMWR Morb Mortal Wkly Rep 2023;72:568–573
37

 stratified by route of administration and immunocompromise status. Overall VE from partial or 1-
dose vaccination was updated to 73% (59-82), with similar results for those with either
administration route. This estimate is similar to the previously reported 75%, but does have a
smaller confidence interval. Overall, VE from 2-dose vaccination was updated to 83% (71-90),
with similar results with either administration route. These updated data suggest that the VE estimates are stable.
Looking at the updated VE estimates for self-reported immunocompromised individuals, the
confidence intervals of the estimates no longer cross zero. However, it is important to note that
the sample sizes are still small within this subset of individuals and have wide confidence
intervals that range from 8-91 for 1 dose and 23- 96 for 2 doses . The point estimates of self-
reported immunocompromised status appear similar but non-significantly lower than that in self-
reported immunocompetent individuals. Notably, as immunocompromised status was self-
reported, it is hard to ascertain the accuracy of this measurement for those who are truly
immunocompromised. For example, people living with well -controlled HIV with CD4 counts
above 350 may have responded that they are immunocompromised. Overall, this data, albeit
encouraging , needs to be interpreted carefully. Ultimately, more work needs to be dedicated to
understanding what VE is in immunocompromised people.
CDC continues to monitor AEs after JYNNEOS using 2 surveillance systems, the Vaccine
Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD). V -safe data
collection for Mpox vaccines was available from November 2022 to March 21, 2023.
Approximately 90% of the reports were submitted during the calendar year 2022. There has
been a relatively small amount of additional safety data accrued during 2023, but no new safety
signals have been identified and no changes have been observed since th e previous ACIP
presentations in February and June 2022. The AEs most commonly reported to VAERS have
been injection site symptoms such as redness, swelling, pain, and itching. Myocarditis and
pericarditis are adverse events of special interest (AESI) and observed rates are consistent with
the expected background rates. VAERS and VSD do not suggest an increased risk for
myocarditis or pericarditis following JYNNEOS vaccination, but the possibility of a small risk
cannot be excluded. The frequencies of local and systemic reactions reported to V -safe after
Mpox vaccine were similar to those report in clinical trials. No new or unexpected safety
concerns have been identified.
In summary, M pox cases and deaths continue to be reported domestically and globally, but no
longer at the same levels observed during 2022. There was an incredible effort and robust
vaccine response, but there is still room for improvement. Less than a quarter of the eligible
population is fully vaccinated with 2 doses. It is important to remember that with little vaccine
implementation outside the US, Canada, or Europe and with a rise in cases in Asia and other
regions, the outbreak is continuing. Modeling data suggest that without vaccination,
transmission of Mpox will continue with sporadic outbreaks. No new safety signals have been
identified from VAERS or VSD and VE appears stable for immunocompetent people.
Discussion Points
Dr. Poehling said she very much appreciated the data using multiple studies to demonstrate that
both doses of JYNNEOS are important for VE. She also highlighted that according to uptake, it
appeared that about 63% of the population who start the JYNNEOS series actually finish both
doses , which is very important. She asked whether there are data on the 8 cases of reinfection,
which is extraordinarily low and they seem to be very mild, in terms of whether they received 1
or 2 doses.
38

   Dr. Minhaj said that in that global case series , 1 individual was vaccinated during that time
period, and there are cases following reinfection that CDC is currently investigating, some of
whom were vaccinated between their first and second infection. However, the number is small
and interpretation of this data can be challenging.
Ms. Bahta asked whether the cases that followed vaccination had been analyzed for method of
vaccine administration.
Dr. Minhaj indicated that they are looking into this, but from VE data is that there does not seem
to be a difference in VE from either administration route.
Dr. Rao added that they have looked to see if there was any pattern. For example, a cluster of
cases occurred in Chicago in May that affected people who were fully vaccinated, and there
does not seem to be an association with those breakthrough infections and the route of
administration. There were breakthrough infections among people who received 2 doses
intradermal ly (ID) , 2 doses subcutaneous ly (SQ), and 1 dose SQ and 1 dose ID . Fewer received
2 doses ID that were breakthrough cases from that cluster. The national data mirrors this .
Dr. Guagliardo added that they have looked at the national case surveillance data and also
assessed the route of administration amongst these breakthrough infections and have not seen
any differences in severity between routes of administration. They are working on publishing
that.
Ms. Bahta noted that her biggest concern was about the complexity of ID vaccination and how
that might have impacted effectiveness, but it sounded like no patterns have been observed.
Dr. Kotton requested additional information about any studies underway looking at
immunocompromised people and, if so, what the timeframe is for getting that information. This
population was devastated by this and were among the deaths reported. Many of them were
immunocompromised and from underserved and other populations.
Dr. Rao confirmed that the deaths are predominantly occurring among people who have
advanced HIV or some other form of severe immunocompromise. These also are individuals
who did not receive any doses of the vaccine. The VE estimates are problematic because a true
VE estimate cannot be extrapolated among immunocompromised people. They also do not
know VE for individuals with that degree of severe immunocompromise. They do recognize this
as an absolute priority. In the multi -jurisdictional study, they are going to attempt to understand
the CD4 counts and viral loads for those patients in order to determine whether they were truly
immunocompromised.
Dr. McCollum added that through the multi -jurisdictional study and the case-control set up for
monitoring of VE , there are opportunities for monitoring. It will be a relatively small subset of
those with well -defined immunocompromise or self-reported immunocompromise. They also are
actively engaged in collaborating on a longitudinal study out of the University of California Los
Angeles (UCLA ) to assess individuals presenting to and receiving care from HIV and sexual
health clinics in the area and monitor them longer -term for self-reported and clinically defined
health events and some of the defined risk factors. That also involve s blood collection for
serology , which will provide a nice additional laboratory component. They also have been
talking to potential collaborators outside of the US to look at populations in endemic regions to
ensure that they are thinking broadly about the scope of data that could be collected. This is an
39

 ongoing story and a top priority to better understand the impact and potential necessity for
vaccine use in these populations.
Dr. Kotton emphasized the importance of assessing people with advanced HIV. She also
encouraged CDC to look outside of that population, given that an estimated 3% of the US
population is immunocompromised.
In terms of the recommendation, Dr. Middleman (SAHM) emphasized the importance of getting
this vaccine into the right people. Gender identity and sexual attraction descriptions do not
necessarily translate into behaviors. In reading the recommendation and in terms of the
epidemiology, her understanding was that it is the behavior that puts people at risk (e.g.,
receptive anal intercourse and anal intercourse in general ). The first line of the recommendation
is confusing and will confuse a lot of people because it is really mixing gender identity
terminology with sexual attraction terminology, which does not translate into behavior. She thought it would be helpful if the recommendations actually stated the risk behavior. She did not believe a transgender male, unless they are engaging in receptive intercourse (e.g., someone
assigned female at birth who is now a trans gender male ) would be in the risk category unless
she was reading that incorrectly. While she understood why it is difficult, she also thought they
should identify the behaviors that put people at risk in order to protect everyone who requires protection.
Dr. Fryhofer (AMA) said that while the safety information was very reassuring, there previously
was a contraindication on giving this vaccine with COVID vaccines. She requested additional
information on this and how they came to that decision.
Dr. Rao clarified that it is not a contraindication or precaution. This is co-administration guidance
that is included in the CDC COVID-19 Interim Clinical C onsiderations and the Interim Clinical
Considerations for the Mpox vaccine. They want to note that it is something people might keep
in mind until there are data that can absolutely rule out even the smallest chance of myocarditis
being potentiated after COVID -19 and JYNNEOS vaccine s are given together. There have not
been any safety signals to suggest that the JYNNEOS vaccine is associated with
myopericarditis . With ACAM2000, the other orthopoxvirus vaccines, there is a definite signal for
which the mechanism is not understood. Therefore, this guidance was included for JYNNEOS.
While the data thus far do not support that, it is not possible to rule out the very smallest chance at this time. She noted that she would discuss this further in her last presentation of this
session, and that CDC STD experts also were involved in the development of this language, so perhaps one of them could speak during the discussion session about exactly why this specific wording was chosen. It is identical to the wording that has been used throughout this particular outbreak response.
EtR F ramework for the JYNNEOS Vaccine
Agam Rao, MD (CDC/NCEZID; CAPT, US Public Health Service) presented the EtR
Framework for vaccination with JYNNEOS vaccine for persons at risk of Mpox. She reminded
everyone that the EtR Framework is a structure to describe information considered in moving from evidence to ACIP vaccine recommendations. It provides transparency around the impact of
additional factors on deliberations when considering a recommendation. For this EtR analysis,
the WG’s question was:
Does ACIP recommend vaccination with the 2-dose* JYNNEOS vaccine series for
persons aged 18 years and older at risk† for mpox?
40

  *Dose 2 administered 28 days after dose 1
• Gay, bisexual, and other MSM, transgender or non-binary people 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 geographic areas where Mpox
transmission is occurring
• Sexual partners of persons with the risks described above
• Persons who anticipate experiencing any of the above
The rationale for the age selection for the EtR Framework is that the JYNNEOS vaccine is
currently licensed for persons 18 years and older. There is an NIH trial underway to study the safety and immunogenicity of JYNNEOS among persons 12 ─17 years of age. When those data
are available, the WG will review them and possibly bring this back to the ACIP. The comparator
is no vaccination, so when going through the EtR domains, the comparison will be the
vaccination versus no vaccination. The outcomes are prevention of disease, severity of disease ,
SAEs, and m yocarditis/pericarditis . As a reminder, the EtR domains include the public health
problem, benefits and harms, values, acceptability, equity, feasibility, and resource use. Dr. Rao
presented the WG’s interpretation of the data for each of these domains and the response to the
questions for each.
Beginning with the public health problem , Mpox cases continue to occur domestically and
internationally, including in clusters, but also in cases that cannot be connected to clusters.
Severe disease and deaths continue to occur as well. Over 1.25 million doses of JYNNEOS
vaccine have been administered in the US, which is great. While it took a lot of effort for that to
happen, national vaccine coverage remains lower than ideal . This is possibly because of the
lower perceived risk of Mpox in the last 6 months. CDC modeling data suggest that larger
outbreaks may occur if vaccine coverage remains less than 50% nationally for persons at risk for M pox. Coverage is currently only about 23% to 24%, so 1 in 4 people who should be
vaccinated are vaccinated at this time. To reiterate, severe disease and deaths are continuing to
occur in predominantly unvaccinated people.
Moving to benefits and harms, there are 3 main sources of VE data, including the CDC Epic
study, the CDC multi -jurisdictional study, and a New York State study. The methodology of
these studies and the data from them were presented during the 2 previous ACIP meetings and
earlier in Dr. Minhaj ’s presentation. To recap, 2 doses of the JYNNEOS series were found to be
better than 1 dose. The estimated VE for preventing Mpox disease is 66% to 89% for the 2-dose
vaccine series. The CDC multi -jurisdictional study continues to collect data. To CDC’s
knowledge, it is perhaps the only source of data that will be continued worldwide. CDC is
attempting to estimate the VE in preventing infections among immunocompetent versus
immunocompromised persons, and recognizes that this is a major gap in understanding.
The ACIP previously recommended use of the 2- dose JYNNEOS vaccine series for 2
populations, including populations at increased risk of occupational exposure to orthopoxviruses
and persons at risk for Mpox during Mpox outbreaks. At that time, ACIP reviewed the GRADE
data and the available VE data. Subsequent data support its effectiveness for the population
impacted by the ongoing outbreak . The WG determined the desirable anticipated effects to be
41

  large. Similarly, there have been no new safety concerns since the previous ACIP votes about
the use of JYNNEOS. The AEs most commonly reported to VAERS have been injection site
symptoms such as redness, swelling, pain, and itching. The WG interpreted these as being
small undesirable anticipated effects. Because the desirable anticipated effects are large and
the undesirable anticipated effects are small, the WG felt that the intervention of vaccination
with JYNNEOS compared to no vaccination is favored.
In terms of the values domain, early in the Mpox outbreak response, multiple national surveys
indicated that there was strong interest in the JYNNEOS vaccine. These data were presented in
detail during the February 2022 ACIP meeting. To summarize the data, during August to
November 2022, greater than 85% of respondents in the American T ransformative HIV Study
(AMETHST)14 were interested in the vaccine. D uring August to December 2022, 50% of Porter
Novelli survey responders who identified as LGBTQ+ felt the vaccination was important to
protect them from Mpox .15 During October to November 2022, greater than 70% of MSM in a
San Francisco survey of persons experiencing homelessness reported that they would accept
or have accepted the vaccine.16 During October to December 2022, an American Men's Interest
Survey (AMIS ) showed that those who were concerned about Mpox were 3.5 times more likely
to be vaccinated.17 In addition to this information, other information also was obtained.
Early in the outbreak , not surprisingly, persons seeking vaccination were supportive of the
JYNNEOS vaccine . One of those study surveys was performed during a study called the DC
PET++ Study,18 which is a CDC and DC Health c ollaboration to follow a cohort of persons at
elevated risk of Mpox exposure in Washington DC who presented for vaccination between
August 2022 through October 2022. This survey of 866  adults found that greater than 85%
agreed or strongly agreed that vaccines for Mpox should be available to anyone who wants the
vaccine , and 82% said that they were likely or very likely to get a third dose if it was to be
recommended; however to be clear, a third dose is not recommended. Another evaluation in
Washington, DC around the same time period supported the same idea.
Also early in the response, studies show ed that there were some conflicting feelings among the
people who are recommended to be vaccinated. A survey was performed by Curtis et al . among
320 persons,19 primarily MSM living in Illinois and at risk for Mpox. Among the respondents ,
24.1% had received 2 vaccine doses, 27.5% had received 1 dose, and 47.5% had received no
doses. Persons who were vaccinated were more likely to have higher education, known
someone with Mpox , expressed concern about their safety, and be less likely to report recent
food insecurity. The Turpin et al. study20 also evaluated this in qualitative interviews performed
with 24 Black MSM attending HIV prevention-related activities in the greater DC area, which is a
very important population. This was early in the Mpox response in May 2022. At that time, there
was not as much availability of the Mpox vaccine as there is now. While there is now sufficient
vaccine to vaccinate all of the people SQ who are recommended to receive the vaccine, a
common concern at that time was the lack of availability of the Mpox vaccine, which implies
interest in the vaccine. Vaccine hesitancy also was expressed commonly , but possibly was
similar to vaccine hesitancy reported for other vaccines.
14 https://grants.nih.gov/grants/guide/rfa-files/RFA- AI-21-018.html
15 https://emoryamis.org/wp-content/uploads/2022/08/2022-Monkeypox-Survey.pdf
16 https://www.cdc.gov/mmwr/volumes/71/wr/mm7135e1.htm
17 Filardo TD. Vaccine. 2023 Sep 7;41(39):5673-5677
18 Hassan, R. (in press). Sexually Transmitted Diseases
19 https://pubmed.ncbi.nlm.nih.gov/37236817/
20 https://pubmed.ncbi.nlm.nih.gov/37510557/
42

   Moving to more recent data, CDC issued a “CDC’s S tate of Vaccine Confidence Insights
Report” in June 2023.21 A month prior to issuing that report in May 2023, an Mpox cluster was
identified in Chicago that predominantly affected people who received 2 doses of the JYNNEOS
vaccine. This report was intended to review Mpox -related discussions on 23 news and social
media outlets in the Chicago area in order to understand the sentiments of the affected
population and develop communication material accordingly. Mpox vaccine hesitancy among
the general public and LGBTQ -affiliated groups was noted. People questioned the effectiveness
and safety of the vaccine and expressed distrust in national reporting. However, when 18
patients who were impacted by that outbr eak were interviewed, 18 agreed to an interview .
Among them were patients who were fully vaccinated, partially vaccinated, and unvaccinated.
Most vaccinated persons felt that the vaccine was effective in reducing severity and some assumed it would prevent infection. Most stated that they would recommend the vaccine to
others . Unvaccinated persons reported initial interest in the vaccine when the supply was limited
and they were unable to receive it. T hey reported they did not seek it again because case
counts decreased so they assumed diminished risk .
In June 2023, CDC performed an online focus group with 52 people to help develop CDC
communication material. Participants were included if they identified as men (including
transgender men and transgender women), were unvaccinated for Mpox, were never diagnosed
with Mpox , were 18─ 45 years of age, and had sex with 2 or more men within the past 6 months.
This essentially was people who were eligible for the Mpox vaccine. The participants were
intentionally of diverse racial and ethnic backgrounds . They were shown various communication
materials developed by the CDC. Exposure to the information about Mpox vaccine safety and
effectiveness and hearing that there is a current threat of Mpox increased their interest in
receiving Mpox vaccine information. Although some of the individuals participated in this focus
group who were not interested in the vaccine or were ambivalent about the vaccine, that
changed after seeing the materials. Many who were disinterested in the vaccine became
interested and said that the current risk of Mpox and protecting their community were
motivating.
To summarize the values domain data, vaccine demand was high early in the outbreak
response when case counts were high. National surveys and interviews early and later in the
outbreak indicated that there is overall interest in JYNNEOS vaccinations, but as with any
vaccine, some people experience vaccine hesitancy. In response to whether the target
population feels that the desirable effects were large relative to the undesirable effects, the WG
answered “probably yes. ” Because interest and intent to get vaccinated varied among the
affected population and a perceived lower risk of Mpox may be contributing to reduced interest
in the vaccine, the WG felt that there was possibly “important uncertainty or variability” in how
much people value the main outcomes.
Moving to the acceptability domain, health departments are supportive of and requested a lot of
the JYNNEOS vaccine and organized vaccination campaigns. An online survey
22 early on
showed that clinicians during July, August, and September 2022 were interested in getting their
patients vaccinated and 69% felt that the US did not have enough Mpox vaccines to handle the
outbreak at that point. A few weeks later on September 12, 2022, a survey showed that 66%
had treated at least 1 Mpox patient, 76% knew where a patient could get the JYNNEOS
vaccine, and 86% wanted to be able to provide the vaccine in their offices.
21 https://www.cdc.gov/vaccines/covid-19/downloads/SoVC- MPOX -062723.pdf
22 https://app.sermo.com/barometer/unitedstates
43

 More recent data come from a Porter Novelli survey of pediatricians and family practice
practitioners with approximately 100 people in each group performed in August 2023. The
survey included 3 Mpox vaccine questions added to a survey on pediatric COVID -19 vaccine
attitudes and behaviors. The responders included family practitioners ( 85%) and pediatricians
(88%) who cared for children 12─ 17 years of age and family practitioners ( 70%) and
pediatricians (60% ) who cared for patients ≥18 years of age. The majority (75%) were in private
practice and 14% practiced in FQHCs. About 54% were part of large practices with over 1500
patients. These data are helpful in terms of understanding themes in general. When asked
whether they would prefer to provide the Mpox vaccine within their practice, family practitioners
more often strongly or somewhat preferred providing the vaccine within their own practice.
Pediatrician s were supportive of the vaccine, but preferred to refer to an outside practice.
As Dr. Minhaj showed earlier, there has been a shift over time in vaccine administration from
public health clinics to medical care centers. If the ACIP votes in favor of the proposed
recommendation, vaccines would be provided in medical centers. However, that already has
been happening. T here has been a statistically significant increase in vaccines provided by
primary care offices, FQHCs, and other health centers . This indicates that providers in these
settings deem the vaccine to be acceptable.
A recent CDC online focus group was performed with HCP to further understand their thoughts,
knowledge, attitudes, and practices related to Mpox . Recruitment done by an external recruiting
firm resulted in a group of 41 participants who were diverse in terms of gender, race/ethnicity,
practice setting, payment methods for patients, and clinical profession. Among the respondents,
61% reported spending ≥60% of their time providing sexual health services ; 59% were private
healthcare settings , 29% were private and publicly funded, and 10% were publicly funded; 54%
were in private practice, 20% were STD/HIV/family planning clinic s, 10% were FQHCs , and
25% were in ED or urgent care settings. Among the respondents, 68% had never managed an
Mpox case , 34%, believe Mpox is a threat to public health, and 32% reported that Mpox is
important to their patient populations. Among respondents, 51% believe that Mpox services
should be integrated into standard care. It might improve access to vaccines, education and
awareness about Mpox for patients, and it would ensure comprehensive STI screening and
testing.
In response to the question regarding whether the intervention is acceptable to key
stakeholders, the WG answer was “yes. ” Health departments and clinicians are supportive of
Mpox vaccines, even if pediatricians would prefer to refer patients to other clinics to receive it.
Family practitioners would like to be able to actually provide the JYNNEOS vaccine in their own clinics. There has been a shift from JYNNEOS provided by public health providers to JYNNEOS
provided by medical center providers, including STI and HIV clinics, where the WG think s these
vaccines will be administered if this recommendation is passed.
Moving to the resource use domain, the vaccine is currently provided through the Strategic
National Stockpile (SNS) that is intended to stockpile therapeutics for bioterrorism preparedness
and other similar preparedness issues. JYNNEOS has been stockpiled for smallpox preparedness, but was provided during this response since it is not commercially available. The
doses would need to be replenished. There has been and will continue to be a significant use of
resources (e.g., shipments , transportation, personnel monitoring) during the peak of this
outbreak. A routine recommendation could be a further drain on the SNS should this vote be
passed. In the future, it is possible that the vaccine will be commercialized. If so, there are
44

   unknown costs that will be associated with that. Therefore, the WG answered that it is
“uncertain” whether the intervention is a reasonable and efficient allocation of resources.
In terms of the equity domain, the WG interpreted this as trying to understand the population
who was impacted by Mpox and felt that there has been a disproportionate impact of Mpox on
gay, bisexual, and other MSM; B lack and Hispanic persons; and persons experiencing
homelessness. Any vaccine administered versus no vaccine administered may decrease the
disparity between the affected population and others. The recommendation would facilitate one-
to-one counseling and information sharing in the privacy of a c linic. Vaccine recommendation
from a clinician is associated with increased vaccine uptake. During September 2023, $5 million
were allocated to community -based organizations (CBOs) to advance Mpox prevention and
vaccination efforts.23 CBOs have played a critical role in the Mpox response so far and are
essential to increasing vaccination coverage among those at risk. Thus far, 42 CBOs have been
funded. If the vaccine is commercialized, there may be an impact on primary sites of vaccination
in health departments. At this point, it would be conjecture to assume exactly what the impact
would be. As previously mentioned, in about 2 to 3 years , it would be necessary to re-assess
this interim recommendation knowing the situation at that time in terms of the epidemiology and
whether the vaccine is commercialized. However, such a recommendation might facilitate
product acceptance of the vaccination because everybody knows that the ACIP has a high bar
for recommending a vaccine. If JYNNEOS vaccine is commercialized in the interim time period,
this also would facilitate insurance companies covering the vaccine.
In response to the question regarding what the impact would be on health equity, the WG group
felt that access to vaccine versus no vaccine may improve the health of persons who are at risk
for impacts, and that a routine recommendation may facilitate vaccinations and that health
equity would be “probably increased. ”
Regarding the feasibility domain, if the ACIP voted to approve the interim recommendation for
JYNNEOS vaccine, the vaccine would continue to be provided through the SNS free of cost to
patients and providers. While there would be a cost overall to the US Government (USG), there
would not be a cost to patients and providers. Mpox provider agreements do not have a
termination date.24 They will continue as long as the vaccine is acquired via the US G program
and can include new providers. In fact, CDC learned that health departments are continuing to
bring on new providers. The $5 million funding that has been provided to CBOs may improve
feasibility in addition to equity. The se CBOs reach hard-to-reach communities and also might
facilitate feasibility for those communities. If the vaccine is commercialized, it would be available
through Medicare, Medicaid, and commercial plans without a co-pay. Uninsured children would
be given the vaccine through the VFC. Some uninsured and underinsured adults could have difficulty , but that would be similar to the difficulty they encounter with other vaccines.
Regarding whether the intervention is feasible to implement, the WG group answered “probably
yes.” SQ vaccine is easy to administer, and providers know how to administer it. Standing orders are available. JYNNEOS can be stored refrigerated for 8 weeks. There has been a
recent shift in vaccine providers to individual clinics , which demonstrates the continued
successful integration of JYNNEOS into provider s’ practices (e.g., STI and HIV care settings,
HIV care pharmacies, LGBTQ+ affirming primary care practices). STI, HIV, and most family
medicine/ internal medicine providers seem to be comfortable providing vaccines, even if some
23 https://www.cdcfoundation.org/pr/2023/mpox-vaccination-CBO-outreach
24 https://www.cdc.gov/poxvirus/mpox/clinicians/provider-agreement.html
45

     pediatricians may refer patients out to other clinics. If commercialized, similar to other vaccines,
the cost of vaccine might impact access to some populations.
To summarize all of the answers provided in the EtR domains, there is nothing clearly
unfavorable. However, there is uncertainty pertaining to the variability and values that people
have about the vaccine in general. This is possibly because they perceive that there is decreased risk, which is not the case. There is uncertainty about commercialization of the
vaccine. Based on all of this, the WG determined that the desirable consequences probably
outweigh the undesirable consequences in most settings. However, several WG members felt
that there was enough information presented that the desirable consequences clearly outweigh
the undesirable consequences despite the uncertainty . Given that more people in a straw poll
supported the “probably outweigh” option, that was what was shown for the balance of
consequences.
In closing, Dr. Rao posted the proposed recommendation a vote and invited input from the ACIP
members and STD colleagues on the language of this vote.
Discussion Points
Dr. Poehling expressed appreciation for the team working with patients and persons who were
directly impacted to co- create the educational materials. While she appreciated the question
that was raised about the verbiage in the proposed interim recommendation defining persons at
risk, there is overwhelming evidence that the primary sentence as stated in the proposed recommendation would be beneficial.
Dr. Poehling made a motion to approve the language as stated, “ACIP recommends
vaccination with the 2-dose JYNNEOS vaccine series for persons aged 18 years and older at risk for Mpox.” Ms. Bahta seconded the motion.
Ms. Bahta stressed that it is really important to understand that in terms of the launching of new
vaccines as well as transitioning from the federal supply to the commercial supply that there will
be decreased access. With that in mind, she emphasized the importance of establishing a Vaccines for Adults (VFA) program. Regarding the potential move to a routine recommendation, she asked for input on the current supply.
Dr. Rao indicated that there is plenty of vaccine for all of the people who are eligible for the
vaccine over the next several years, including people who become eligible during that time period.
Dr. Daley indicated his support for the proposed recommendation and requested a reminder
about the duration of protection from vaccination. Dr. Rao said they are hoping to continue to evaluate duration of protection through continuing
VE work. To her knowledge, the multi -jurisdictional study is the only one out of the 3 studies that
will be continuing, though perhaps the New York State study also will be continuing. What is
known is that the pre-licensure data indicated that an anamnestic response to the vaccine
occurs for up to 2 years after the primary 2-dose series. The only reason a booster frequency of
2 years was proposed for persons at occupational risk for orthopoxviruses was that nobody had
evaluated a time point later than 2 years. In the Democratic Republic of Congo (DRC), CDC has
a vaccine study that is looking into this. It appears that people have mounted a robust response
5 years after the initial primary dose series , but they want to evaluate that more before
46

 confidently express ing this . She called on Drs. McCollum and Panayampalli who led the DRC
work to comment further.
Dr. Panayampalli added that participants were classified as those having never received the
vaccine and those who received the vaccine during childhood. Even after several decades,
people who received childhood vaccination demonstrated a robust and anamnestic response.
Those individuals probably received replicating vaccine previously. JYNNEOS is a non -
replicating vaccine, so they also wanted to s ee if JYNNEOS has a similar effect. As Dr. Rao
mentioned, 5 years after people received JYNNEOS, regardless of whether any circulating
antibodies were detected, a robust increase is seen in the immune response 7 days after a
boost.
Dr. Cineas requested information on a timeline for a recommendation for adolescent patients
who are at risk .
Dr. Rao reiterated that the reasons the proposed recommendation was for persons 18 years of
age and older was because the vaccine is currently licensed in that population. There are going to be NIH data from a trial among adolescents 12─17 years of age, hopefully in 2024. She
noted that she would explain the clinical guidance data further in her next presentation.
Dr. Beigel (NIH) reported that the adolescent study was fully enrolled in September 2023, which
means the peak immunogenicity visits at 42 days occurred a few days before this meeting. It is
designed to include a 1- year follow -up, which is in October 2024 for the full dataset. NIH can
discuss with the ACIP and Bavarian Nordic about early analyses .
Dr. Zahn (NACCHO) noted that the State of California has simplified the recommendation
indication that a person who is a practicing MSM who has HIV is recommended to receive the
vaccine. He has been a fan of that simpler recommendation, given that persons at risk may not
recognize they are at risk and/or depending upon the setting, HCP might not be comfortable
going through all of the potential risks. There also is the issue of stigma because someone has
practiced certain behaviors that are risk factors. While they do not have enormous uptake, he
would be disappointed in not continuing to have a broad recommendation since they do continue to have sporadic disease in Southern and Northern California. Outreach to specific community settings has proven to be and will continu e to be valuable. Having the continued
support for their CBO partners and to public health to provide outreach over time is going to be
important.
Dr. Rao agreed with the importance of continuing to support CBOs because they do very
important work, particularly for this population. She noted that a lot of thought was put into whether the recommendation could be simplified, but this is an infection that occurs when there
are certain behavior risk factors. To recommend the vaccine to anyone who has HIV and/or
anyone who is MSM perhaps would result in giving the vaccine to people who do not need it but
might be concerned about getting Mpox even though they are in a monogamous relationship
and do not meet the criteria.
Dr. Quilter added that they were trying to strike a balance. She appreciated the comments about
wanting to avoid stigma and to simplify the recommendation for providers, but also wanting to
ensure that the vaccination being given to those who are most at risk for Mpox exposure. The
version proposed was tweaked from an even more complicated version the first time around to
achieve that balance.
47

 Dr. Rao asked whether Dr. Spicknall, as a modeling expert in the Division of STD prevention,
had any thoughts about just how much bigger the population would be if it was referring to all
MSM or all people with HIV versus how it is described in the proposed recommendation.
Dr. Spicknall said that in terms of a larger population, it would go from roughly 2 million to 4 to 6
million people. The scope would be enlarged greatly such that folks who may not benefit from
this vaccine for the reasons described would be vaccinated.
Dr. Drees (SHEA) observed that the list of people who are at risk in the proposed recommendation did not mention occupational exposures, and she wondered whether that was intentional because it would be a separate vote or if it needed to be included in this recommendation.
Dr. Rao indicated that occupational exposures intentionally were not included in this proposed
recommendation because this is intended to be PrEP for the population at risk of acquiring Mpox in the current outbreak. There already are standing occupational recommendations for laboratorians and HCP on which the ACIP voted in February 2022 in terms of who needs to be vaccinated during an outbreak. Because so few healthcare- association infections have been
acquired, it is not routinely recommended for clinicians who are providing care to patients who have or might have Mpox. Being in the midst of an outbreak, many laboratorians have been and
can continue to be vaccinated.
Dr. Drees (SHEA) said that “wearing her other hat” as a practicing HIV provider that her state also allows anyone with HIV to be vaccinated. Clinicians have to talk about many vaccines with
their populations, so she does not routinely offer Mpox vaccine to every person living with HIV
because she knows many of them are not at risk.
Dr. Middleman asked about the rationale for inclusion of non -binary and transgender people.
Transgender males are assigned female at birth, so it was not clear to her what the risk factors
were if not just receptive anal intercourse and if there was something different about
transgender males and non-binary people that put them at higher risk. She emphasized that she wanted to make sure that they were not making assumptions of behavior or increased risk based on gender identity status.
Dr. Quilter indicated that the population of persons at increased risk in the proposed
recommendation was based on gender identity and sexual orientation. She did not know if there
was enough information yet to specify a behavior. Based on how Mpox is transmitted through
intimate or sexual contact, it could be any skin-to -skin contact with mucosal infections. It is
possible through oral sex, insertive or receptive anal sex, or other mucosal exposure. The
decision about persons at risk was data-driven. A CDC MMWR was published earlier in the year
that was dedicated specifically to the epidemiology of Mpox in persons who are transgender or
non-binary people. The authors found that these populations  were disproportionately affected by
the Mpox outbreak. Cisgender women have been minimally impacted. There has been a
disproportionate impact on Mpox transgender and non-binary people. The exact wording used
in the MMWR was reviewed and endorsed by CDC’s health equity experts so that the
recommendation could be as inclusive as possible and ensure that the people who are known to
be at risk are getting vaccinated.
Dr. Rao added that they know of cases of people lying very close together without clothing on and having contact with the lesions in the genital region. There have been people who said they
48

  had penetrative sex, receptive sex, heterosexual women who seem to have acquired it from
bisexual men.
Dr. Spicknall pointed out that the modeling evidence suggests that not only are personal
individual -level risk factors and behavioral adaptations occurring, but also it is a group of people
acting together that in effect decreases transmission.
Dr. Lee recapped that in the adolescent population, Dr. Middleman was highlighting the
assumption issue. As they begin to think about the adolescent age group, they will have to
question the recommendations to ensure that they are not reinforcing potential stereotypes.
Dr. Boucher (ASPR/ HHS ) reported that since the identification of Mpox cases in the US in May
2022, Administration for Strategic Preparedness and Response (ASPR) has shipped over 1
million vials of JYNNEOS to federal and jurisdictional partners. As Dr. Rao and others
mentioned, JYNNEOS was developed by Bavarian Nordic and USG partners like the Biomedical Advanced Research and Development Authority (BARDA), and others as part of the
nation’ s smallpox preparedness program. Given its safety profile, particularly for
immunocompromised individuals , and effectiveness in reducing the frequency and severity of
infections, there was a strong justification to use doses held in the SNS to support the response.
In continuing to move beyond the acute phase of the response, ASPR is supportive of the
transition of JYNNEOS to commercial distribution as the next correct step in ensuring continued
access for those who wish to get vaccinated for Mpox. ASPR also is committed to ensuring a
seamless transition if this does go to commercial distribution. There will not be gaps in the
availability of JYNNEOS as ASPR “passes the baton” onto its partners at Bavarian Nordic. In
January 2023, ASPR migrated jurisdictional ordering to a threshold-based system that is similar
to that used for COVID v accines and therapeutics. At that time, about 400,000 vials were put
into the combined thresholds across 64 jurisdictions. To date, about 57,000 of those have been
ordered. That means that there are still well over 300,000 vials available immediately to
jurisdictions anytime they need to restock existing vaccination sites or supply new ones. ASPR
will keep this supply reserve for the jurisdictions as they work with Bavarian Nordic and HHS
partners at CDC, CMS , and several others over the coming months in order to plan and execute
a smooth handoff. Regarding the question earlier about the largest supply , through ASPR’s
partnership with Bavarian Nordic and a lot of great efforts that they have made to expand
manufacturing capacity and deliveries over the last year and a half, ASPR significantly built its
JYNNEOS inventory in that period. If the JYNNEOS vaccine transitions to commercial
distribution and there is a point at which demand is outpacing BN’s manufacturing capacity,
ASPR would still consider itself to partner with Bavarian Nordic and would be happy to work
through ways that they might be able to provide support to avoid any shortages. He recognized
that there were many people participating in the meeting who play viral roles in providing care to
patients and reducing Mpox cases. On behalf of all of his colleagues at ASPR, he expressed
gratitude for everything they do to keep people safe and healthy and thanked them for their
partnership throughout the response.
Lee Ann Kimak (Bavarian Nordic) indicated that she is the US Commercial Lead at Bavarian
Nordic . On behalf of Bavarian Nordic, she thanked the WG and the ACIP for their tremendous
efforts and their careful deliberations on this important public health issue. Bavarian Nordic is
very proud to have partnered with the US G in the successful response to meet the Mpox
outbreak, including the rapid deployment of JYNNEOS. They also realize that vaccine access
challenges remain. They believe that the routine preventative recommendation for at-risk
populations under consideration by the ACIP is a critical step forward in addressing these
inequities and access challenges. This recommendation would allow providers and retail
49

     pharmacies to administer the vaccine where people are most comfortable seeking one, whether
that is at the pharmacy, their doctor's office, or their neighborhood health clinic. If the committee
votes for a routine recommendation for the at-risk population, putting Mpox vaccine on the
immunization schedule, Bavarian Nordic very much looks forward to commercializing JYNNEOS
in the US. They have a robust manufacturing process and ample supply to meet the need. They
also have an unwavering commitment to public health and look forward to working with the
agency and healthcare providers in the community to make this vaccine accessible to
individuals at risk.
Dr. Sanchez asked whether Ms. Kimak could comment on the anticipated price of the
JYNNEOS vaccine .
Lee Ann Kimak (Bavarian Nordic) reported that the intended list price will be in the range of
$200 to $270 per dose. The list price is then negotiated down in the contracting phase,
depending upon the particular reimbursement mechanism. It comes down by 25% to 30% or
more , which is the range for the wholesale acquisition cost.
Review of Voting L anguage and Clinical G uidance
Agam Rao, MD (CDC/NCEZID; CAPT, US Public Health Service) indicated that this
presentation was dedicated to guidance about whether the proposed interim recommendation
should be passed and next steps. This guidance refers to vaccination before exposures to
Mpox , not post-exposure prophylaxis (PEP). Much of the guidance is similar or identical to what
she presented during the June 2023 ACIP meeting. All of this guidance refer s to the individuals
listed in the footnote included with the proposed interim recommendation who would be eligible
for the vaccine and for PrEP only.
JYNNEOS is not licensed for persons <18 years of age. There are no pre pre-licensure studies
in this population. However, vaccine has been administered to this population. While a good
number of adolescents 12─17 years of age received a first dose of the JYNNEOS vaccine, CDC
has not received any concerning safety signals in this population or VAERS reports of SAEs in
this age group. For the NIH clinical trial in progress focused on s afety and immunogenicity of
JYNNEOS in persons aged 12─ 17 years of age, it sounds like data may be available by the end
of 2024 and perhaps the earliest it could be presented to ACIP would be in  2025. That is why
guidance is proposed saying that adolescents at risk for Mpox may receive the JYNNEOS
vaccine before an exposure, which refer to adolescents with risk factors.
In terms of pregnancy or breastfeeding, available human data are insufficient to determine
whether the vaccine has any risks in pregnant persons. However, animal model data are
mentioned in the package insert. This includes models involving rats that have shown no
evidence of harm to the developing fetus. No AEs have been reported to the US vaccine safety
surveillance systems . They do not have data showing how many pregnant persons have
received the vaccine during this response. However, it is reassuring that at least there have not
been VAERS reports of anyone actually indicating that an AE was in a pregnant person.
Similarly for breastfeeding persons, this has not been evaluated and there have been no AE
reports reported in the US vaccine safety surveillance systems. JYNNEOS is not
contraindicated in pregnancy or while breastfeeding, and CDC has stated such in the
occupational recommendations that were published about the use of JYNNEOS in 2022. After
discussing this with the American College of Obstetricians and Gynecologists (ACOG) WG
member and others, the decision was made for the clinical guidance to be, “Pregnant or
breastfeeding persons at risk for Mpox may receive the JYNNEOS vaccine before an exposure.”
50

   Again, this is referring to those people with the risk factors, not all pregnant or breastfeeding
persons.
Moving to HCP, healthcare-associated Mpox infections have been rare and typically associated
with sharps injuries or exposure in the absence of personal protective equipment (PPE). There
have been very few cases, as discussed during the June 2023 ACIP meeting, especially among people using the PPE that they should be using. HCP at risk for Mpox because of the risk factors described (e.g., MSM with more than one sexual partner) should be vaccinated.
However, this recommendation is not because of occupational risk. The guidance is that
JYNNEOS is not recommended as a routine vaccination for healthcare personnel unless sexual
risk factors are present.”
There is a known risk for m yopericarditis after ACAM2000, which is the other orthopoxvirus
vaccine used in the US. Given that the mechanism is unknown, a theoretical risk with
JYNNEOS has not been ruled out yet. There is a known risk after COVID- 19 vaccines,
particularly in adolescent and young adult males. That is the reason that the CDC websites for
COVID -19 and Mpox vaccines provide interim guidance for co-administration of JYNNEOS with
COVID -19 vaccines . CDC’s interim guidance in the clinical considerations for coadministration
of JYNNEOS vaccine with COVID -19 vaccines
25 states that, “There is no required minimum
interval between receiving any COVID -19 vaccine and JYNNEOS vaccine (e.g., for Mpox
prevention), regardless of which vaccine is administered first. People, particularly adolescent
and young adult males, who are recommended to receive both vaccines might consider waiting
4 weeks between vaccines. This is because of the observed risk for myocarditis and pericarditis
after receipt of ACAM2000 orthopoxvirus vaccine and COVID -19 vaccines and the hypothetical
risk for myocarditis and pericarditis after the JYNNEOS vaccine. However, if a patient's risk for Mpox or severe disease due to COVID -19 is increased, administration of JYNNEOS and
COVID -19 vaccines should not be delayed.”
The WG talked about the JYNNEOS vaccine and immunoglobulin products in detail, and it was
presented to ACIP during the June 2023 meeting. The reason this came up is because technically , the JYNNEOS vaccine is a live virus vaccine. However, it is a non-replicating virus
vaccine. The WG determined that there are no precautions necessary if JYNNEOS is
administered in close temporal proximity to intravenous immunoglobulin (IVIG ). With regards to
vaccinia immunoglobulin intravenous (VIGIV ), which is a product that basically is pooled from
persons who are vaccinated with ACAM2000, it perhaps could interfere with the immune
response to the JYNNEOS vaccine. Ideally, administration of JYNNEOS should be delayed if
VIGIV was recently administered. The reason that VIGIV is probably administered to a patient is
a severe manifestation of Mpox . At this time, those are persons for whom vaccination would not
be recommended since they have acquired Mpox. Currently, the recommendation is that people
who have recovered from Mpox do not need to be vaccinated. Therefore, this is not likely to
come up very often if at all. If it does come up, a public health consultation should be obtained
for case-specific guidance.
As far as contraindications and precautions , JYNNEOS was licensed for prevention of smallpox
in addition to prevention of Mpox .
26 Because smallpox is nearly always life -threatening, there
are no absolute contraindications for the use of JYNNEOS to prevent smallpox. That is why the
package insert does not list an absolute contraindication. However, the considerations may be
different for Mpox. Consistent with contraindications and ACIP routine schedules, the WG
25 https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us.html
26 https://www.fda.gov/media/131078/download
51

 proposed stating that JYNNEOS is contraindicated in patients with severe allergic reaction,
(e.g., anaphylaxis) after a previous dose of the vaccine or to a vaccine component. Under
precautions, the WG proposed making a statement similar to what is listed for pretty much all
vaccines, “Precautions: Moderate or severe acute illness, with or without fever .”
For other administration guidance, the WG wanted to stress that completion of the 2- dose series
should be encouraged. If there is one message that hopefully comes from this meeting, it is that
Mpox cases are still occurring, and this is not over. If people got only 1 dose or did not seek the
vaccine because there was not as much availability as last year, the hope is that they will reach
out now and get vaccinated as much as possible. Getting the second dose into arms would be
really great for those individual patients , their friends , and others. The second dose should be
administered at about 28 days after the first dose. However, the second dose can still be
administered even if over a year has elapsed. Restarting the series is not required and the
second dose should be administered as soon as possible.
In terms of next steps, Dr. Rao explained that the Mpox WG is not going away completely . They
will publish the 2 MMWR ACIP recommendations about the use of JYNNEOS during outbreaks
and the use of JYNNEOS among persons at risk during the ongoing Mpox outbreak in 2024
because they are compl ementary. Once the data are available from the NIH, perhaps the WG
will reconvene toward the end of 2024 and potentially will present the data to the ACIP in early
2025. If passed, the recommendation will be revisited in 2 to 3 years when more data are
available about the epidemiology to help decide whether this recommendation should be
continued. The WG will revisit the E tR review, epidemiology , cost-effectiveness analys es, and
other data and will present that to the ACIP to determine whether this should be continued. In
the interim, this recommendation would exist if it is passed. If the vaccine becomes
commercialized, there would be additional tasks that would need to be addressed.
Discussion Points
Dr. Poehling expressed appreciation for the tentative timeline and the thought of continuing to
evaluate the impact to make sure the recommendations are precise and are having the desired
impact. She stated that one question that we focus on for safety is myopericarditis. In the doses
of JYNNEOS administered in the United States, we have not seen cases of myopericarditis in VAERS or VSD, but that does not exclude it occurring rarely, is that correct?
Dr. Duffy expressed that is the correct understanding on safety for JYNNEOS.
Dr. Loehr asked if Ms. Kimak could comment on how long the manufacturer thinks it would take
to commercialize this vaccine.
Lee Ann Kimak (Bavarian Nordic) indicated that Bavarian Nordic began taking steps toward
commercializing the product as soon as they learned that the ACIP would be considering a
recommendation. If JYNNEOS is routinely recommended for those at risk of Mpox , this would
allow Bavarian Nordic to move forward with some of the steps toward commercial insurance
coverage. They anticipate that it will take a number of months to negotiate these contracts and
be prepared to work through all of the necessary steps with a variety of payers in terms of
setting up the distribution channels to store and administer the vaccine. As with the commercial
transition of the COVID vaccines, this process can take some time. However, she would not
foresee it being outside of the 6- to 9-month range.
52

 Dr. Loehr emphasized the need for a cost-benefit analysis. The ACIP basically would be voting
on and approving the interim recommendation which could be extremely costly, yet they have
no sense of that. He noted that while he was in favor of the recommendation based on the
current status, he wanted it to be reviewed as soon as the new data become available.
Dr. Lee pointed out that all of the ACIP’s recommendations are interim and could be revisited at
any moment. She suggested dropping the terminology “interim recommendation” similar to what
they did for pneumococcal vaccines. The ACIP does not have “strong recommendations ” or “not
strong recommendations.” She agreed with Dr. Loehr’s point about the cost-effectiveness analysis . The unusual nature by which this vaccine is coming to market makes it somewhat
complicated.
As a reminder, public comment was presented prior to the votes. However, the votes were
combined in this proceedings document with their respective sessions for the purpose of
continuity.
Vote: Mpox Vaccine Recommendation
Agam Rao, MD (CDC/NCEZID; CAPT, US Public Health Service) presented the proposed
recommendation for a vote as follows:
ACIP recommends vaccination* with the 2-dose† JYNNEOS vaccine series for persons
aged 18 years and older at risk for Mpox§
*Interim recommendation that ACIP will revisit in 2-3 years
†Dose 2 administered 28 days after dose 1
§Persons at risk:
• Gay, bisexual, and other men who have sex with men, transgender or nonbinary people 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
Motion/Vote: Mpox Vaccine Recommendation
Dr. Poehling moved to accept the Mpox vaccine recommendation language as presented, which
Ms. Bahta seconded. No COIs were declared. The motion carried with 14 affirmative votes, 0 negative votes, and 0 abstentions. The disposition of the vote was as follows:
14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, Poehling, Sanchez, Talbot
0 Opposed: N/A
0 Abstained: N/A
53

 Vote: VFC Mpox R esolution
Dr. Jeanne Santoli (CDC/NCIRD) presented the VFC Mpox Resolution for the ACIP’s
consideration and vote. The purpose of this resolution is to add a vaccine for the prevention of
Mpox to the V FC program. The eligible groups are as follows:
Children aged 18 years of age at increased risk of Mpox, including:
Persons who are gay, bisexual, and other men who have sex with men, transgender
or non-binary people who in the past 6 months have had:
− At least 1 sexually transmitted disease
− More than 1 sex partner
− Sex at a commercial venue
− Sex in association with a large public event in a geographic area where Mpox
transmission is occurring
Persons who are sexual contacts of the persons described above
Persons who anticipate experiencing any of the situations described above
The recommended schedule and dosage intervals are 2 doses given 28 days apart . The
recommended dosages refers the reader to the product package inserts. Similarly for
contraindications, there is a referral to the package insert and precautions include moderate or
severe acute illness with or without fever. There will be the statement referencing future
published recommendations that will be incorporated by reference.
Given the discussions, the following bullets convey vaccine availability through the VFC:
Mpox vaccines will not be available through the VFC program immediately following the
passage of this resolution because they are not yet commercially available.
At this time, Mpox vaccines remain available under the HHS Mpox Vaccination Program .
Following the passage of this resolution, CDC will begin the steps necessary to solicit
for/award contracts for Mpox vaccines.
The timeline for availability of Mpox vaccines commercially or through the VFC program has
not yet been finalized.
Discussion Points
Dr. Talbott pointed out that this vaccine is the perfect example of why a Vaccines for Adults
program is needed.
Dr. Talbot made a motion to accept this language as proposed. Dr. Poehling seconded
the motion.
54

Motion/Vote: VFC Mpox Resolution
Dr. Talbot moved to accept the VFC Resolution for the Mpox vaccine recommendation as
presented, which Dr. Poehling seconded. No COIs were declared. The motion carried with 14
affirmative votes, 0 negative votes, and 0 abstentions. The disposition of the vote was as
follows:
14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally,
Poehling, Sanchez, Talbot
0 Opposed: N/A
0 Abstained: N/A
ADULT RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINES
Introduction
Camille Kotton, MD (Chair, Adult RSV WG) introduced the Adult RSV WG. She reminded
everyone that in June 2023, the ACIP voted to recommend that adults ≥60 years of age may
receive a single dose of RSV vaccine using shared clinical decision-making.27 There are 2 FDA-
approved RSV vaccines , which are as follows:
RSVPreF3 (Arexvy, GSK) is a 1 -dose adjuvanted (AS01E) recombinant prefusion F protein
(preF) vaccine.
RSVpreF (Abrysvo , Pfizer) is a 1-dose recombinant preF vaccine.
Issues under discussion since the June ACIP meeting include that the WG reviewed CDC
safety surveillance plans for RSV vaccination in adults ≥60 years of age. GSK has shared with
the WG results of an immune-bridging study showing non-inferior hum oral immune responses to
RSV vaccination in immunocompetent adults 50 ─59 years of age compared with
immunocompetent adults ≥60 years of age in whom efficacy was demonstrated. To be clear,
this is just a serology study, not an efficacy study. The WG discussed the potential role of RSV
vaccination in adults younger than 60 years of age, including subpopulations who would benefit
most from vaccination and equity implications . The WG reviewed CDC vaccine surveillance
safety plans for RSV vaccination in adults ≥60 years of age, including V -safe that has launched
for older adult RSV vaccination. Dr. Kotton encouraged everyone listening to this meeting who
interacts with people who are getting the adult RSV vaccine to encourage them to sign up for V -
safe so that there will be as much clinical information about this vaccine as possible.
This s ession did not include RSV vaccine uptake data or safety surveillance data as those data
were premature early into the vaccination program. U ptake and safety results will be shared
during a future ACIP meeting. This session included the following topics:
27 https://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm
55

  RSVPreF3 safety and immunogenicity in adults 50– 59 years of age, compared with adults
≥60 year s of age
Epidemiology of RSV hospitalization in adults, with a focus on adults 50– 59 years of age
WG considerations regarding RSV vaccination in adults 50– 59 years of age
GSK Safety and Immunogenicity in Persons 50-59 Years of Age
Susan Gerber, MD (Medical Director, Adult RSV vaccines, GSK) presented an RSVPreF3 +
AS01 E (AREXVY) safety and immunogenicity update in adults 50─ 59 years of age. Beginning
with a brief background of RSV disease i n this population, there is substantial RSV burden and
unmet medical need in adults 50─ 59 years of age. Rates of RSV -associated hospitalizations
and medically -attended RSV illnesses are relatively high in this age group related to the
development of immuno senescence and increased incidents of certain comorbidities. Published
incidence rates likely substantially underestimate RSV burden due to lack of awareness,
standardized testing, and under -detection within surveillance studies. Chronic underlying
medical conditions or co -morbidities that are associated with severe RSV disease such as
chronic obstructive pulmonary disease (COPD ), congestive heart failure, diabetes, asthma,
chronic liver disease (CLD), and chronic kidney disease (CKD) are prevalent in this age group.
Additionally, observed disparities by race and ethnicity are particularly pronounced with respect to hospitalization rates among middle-aged adults 50─ 64 years of age.
Data from the CDC surveillance platform, RSV-NET, on unadjusted RSV-associated
hospitalization rates by race and ethnicity for the last 5 seasons for persons 50─ 64 years of age
identified consistent disparities among Hispanic, American Indian/ Alaska Native (AI/AN), and
Black Americans as compared with White non- Hispanic Americans.
28 Along these lines, a
recent presentation at IDW eek 2023 from Dr. Angela Branch e and colleagues showed that
young and middle-aged adults with certain underlying co-morbid conditions are at high risk for
RSV-associated hospitalization, with potentially a disproportionate risk for Black and Hispanic
middle-aged adults.
Based on this unmet medical need, GSK conducted a study to evaluate their RSV vaccine in
immunocompetent adults 50─ 59 years of age.29 The primary objective was to demonstrate the
non-inferiority of the hum oral immune response after RSVPreF3 + AS01 E vaccine administration
in adults 50 ─59-years of age with and without co-morbidities well -documented to be related to
RSV-associated severe disease compared to older adults ≥60 years of age. GSK previously
established high vaccine efficacy against symptomatic RSV illness in adults ≥ 60 years of age.
Primary endpoints were to evaluate the non-inferiority of RSV-A and RSV -B neutralization titers
at 1 month following vaccine administration for 2 adult groups 50─59 years of age, with and
without co- morbidities associated with RSV lower respiratory tract disease (RSV -LRTD ), as
compared to adults ≥60 years of age. Success criteria is defined as the upper limit of the 2-
sided 95% confidence interval for the geometric mean titer (GMT) ratio of ≤ 1.5 and the
seroresponse rate difference of ≤ 10%. Additional immunogenicity endpoints will be examined at
6 and 12 months as the study continues . Frequency of CD4+ T cells were assessed in subsets
of adults 50 ─59 years of age and ≥60 years of age to evaluate the cell -mediated immune
response. Safety endpoints also were included.
28 Graphs independently created for GSK from original data; A/PI, Asian and Pacific Islander, AI/AN, America Indian or Alaska
Native; CDC, https://www.cdc.gov/rsv/research/rsv-net/dashboard.html  (accessed October 2023)
29 ClinicalTrials.gov. NCT05590403. https://www.clinicaltrials.gov/study/NCT05590403; (accessed September 2023)
56

 The study is a randomized, placebo- controlled, observer-blind, multi -country study. Cohorts 1a
and 1b were randomized 2:1 to receive vaccine or placebo. Cohort 1a are adults 50─59 years
of age with co-morbidities associated with RSV- LRTD and Cohort 1b are adults 50─59 years of
age without co-morbidities associated with RSV -LRTD. Cohort 2a are adults ≥60 years of age.
This standard immune -bridging, non- inferiority approach has been developed to bring vaccines
faster to those at high risk for severe disease, such as COVID -19 vaccines, and was developed
and agreed upon in consultation with the FDA. This presentation focused on the preliminary 1-
month immunogenicity and 6-month safety results. This study included participants from 8
countries; approximately 23% were from the US. Demographic and clinical characteristics were
well-balanced between the vaccine and placebo groups. O f the adults ≥60 years of ag
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