MEETING OF THE ADVISORY 

COMMITTEE ON IMMUNIZATION 

PRACTICES (ACIP)

JUNE 22-23, 2022

SUMMARY MINUTES

TABLE OF CONTENTS

MEETING PURPOSE ................................................................................................................................... 4

WEDNESDAY: JUNE 22, 2022.................................................................................................................... 4

WELCOME AND INTRODUCTIONS......................................................................................... 4

Call to Order/Roll Call ............................................................................................................ 4

Announcements..................................................................................................................... 4

INFLUENZA VACCINE.............................................................................................................. 5

Session Introduction .............................................................................................................. 5

Preliminary Estimates of 2021–2022 Seasonal Influenza VE against Medically Attended 

Influenza ................................................................................................................................ 5

Discussion Summary ............................................................................................................. 6

Influenza Vaccines for Persons Aged ≥65 Years: EtR Framework........................................ 6

Influenza WG: Summary/Proposed Recommendations for the 2022-2023 Influenza Season

.............................................................................................................................................22

Vote #1: Influenza Vaccines for Persons ≥65 Years of Age ................................................25

Vote #2: Proposed 2022-2023 Recommendations..............................................................26

PNEUMOCOCCAL VACCINES...............................................................................................27

Session Introduction ............................................................................................................27

PCV15 Pediatric Clinical Development Program Update ....................................................28

Economic Analysis and Public Health Impact of PCV15 Use in Children............................31

Updates to the EtR: Use of 15-valent Pneumococcal Conjugate Vaccine in Children ........34

Proposed Recommendations for PCV15 Use in Children ...................................................40

Vote: PCV15 Vaccine Use in Children.................................................................................43

VFC Vote: PCV15 Vaccines in Children ..............................................................................43

MEASLES, MUMPS, AND RUBELLA (MMR) VACCINE ........................................................44

Session Introduction ............................................................................................................44

Priorix for Prevention of Measles, Mumps, and Rubella......................................................44

Discussion Summary ...........................................................................................................49

Vote: MMR Vaccine.............................................................................................................52
ACIP Meeting Summary June 22-23, 2022

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HUMAN PAPILLOMAVIRUS (HPV) VACCINE .......................................................................53

Session Introduction ............................................................................................................53

National and State-Level HPV Vaccination Coverage.........................................................54

Impact of the US HPV Vaccination Program on HPV-Associated Outcomes......................56

1-Dose HPV Vaccination: Overview of Current Evidence ...................................................58

Discussion Summary ...........................................................................................................63

PUBLIC COMMENTS JUNE 22, 2022 ....................................................................................64

Overview..............................................................................................................................64

Public Comments.................................................................................................................65

THURSDAY: JUNE 23, 2022 .....................................................................................................................69

WELCOME & INTRODUCTIONS............................................................................................69

Call to Order/Roll Call ..........................................................................................................69

AGENCY UPDATES................................................................................................................69

Centers for Disease Control and Prevention .......................................................................69

Centers for Medicare and Medicaid.....................................................................................70

Food and Drug Administration .............................................................................................70

Health Resources and Services Administration...................................................................71

National Institutes of Health.................................................................................................72

Office of Infectious Disease and HIV/AIDS Policy ...............................................................72

CORONAVIRUS DISEASE 2019 (COVID-19) VACCINES.....................................................73

Session Introduction ............................................................................................................73

Burden, Prevalence, and Trends of Long-Term Sequelae of SARS-CoV-2 ........................74

Updates on Safety of COVID-19 Vaccines in Children and Adolescents ............................79

Vaccine Safety Technical Work Group (VaST) Assessment ...............................................84

Safety & Immunogenicity of Moderna 2-Dose Primary Series in Children Ages 6-17 Years

.............................................................................................................................................89

EtR Framework: Moderna COVID-19 Vaccine in Children & Adolescents Ages 6-17 Years

.............................................................................................................................................94

Clinical Considerations Update..........................................................................................103

Discussion Summary (Oliver & Hall)..................................................................................105

Votes: Moderna COVID-19 Vaccine in Children & Adolescents Ages 6-17 Years ............108

RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINES......................................................109

Session Introduction ..........................................................................................................109

RSV Virion and Vaccine Products .....................................................................................110

Discussion Summary .........................................................................................................113

RSV Seasonality in the US and the Burden of RSV in Children........................................113

Epidemiology and Burden of Respiratory Syncytial Virus in Older Adults in the US .........117
ACIP Meeting Summary June 22-23, 2022

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Nirsevimab For The Prevention of RSV Disease In All Infants..........................................120

MONKEYPOX INFORMATIONAL SESSION........................................................................125

Situational Update .............................................................................................................125

Medical Countermeasures................................................................................................. 130

PUBLIC COMMENTS JUNE 23, 2022 ..................................................................................136

Overview............................................................................................................................136

Public Comment ................................................................................................................137

CLOSING REMARKS............................................................................................................141

CERTIFICATION ......................................................................................................................................142

ACIP MEMBERSHIP ROSTER ................................................................................................................143

ACRONYMS USED IN THIS DOCUMENT ..............................................................................................152
ACIP Meeting Summary June 22-23, 2022

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MEETING PURPOSE

The United States (US) Department of Health and Human Services (HHS) and the Centers for 

Disease Control and Prevention (CDC) convened a meeting of the Advisory Committee on 

Immunization Practices (ACIP) on June 22-23, 2022. The meeting took place remotely via 

Zoom, teleconference, and live webcast. This document provides a summary of the meeting, 

which focused on Influenza; Pneumococcal; Measles, Mumps, Rubella (MMR); Human 

Papillomavirus (HPV); Coronavirus Disease 2019 (COVID-19); Respiratory Syncytial Virus 

(RSV); and Monkeypox Vaccines. Please note that while public comments were provided each 

day prior to votes and votes were made at the end of each day, votes are included in this 

document with their respective topical sessions for ease of reading what transpired with each 

topic area. 

WEDNESDAY: JUNE 22, 2022

WELCOME AND INTRODUCTIONS

Call to Order/Roll Call

Dr. Grace Lee (ACIP Chair) called to order and presided over the first day of the June 22-23, 

2022 ACIP meeting. She conducted a roll call, 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. The following conflicts of interest (COIs) were declared:

 Dr. Kevin Ault declared a COI with the HPV discussion, given that he acted as a consultant 

for PANHPVAX, which is in the process of developing an HPV vaccine.

Announcements

Dr. Melinda Wharton (ACIP Executive Secretary, CDC) welcomed everyone and noted that 

copies of the slides for the day were available on the ACIP website and were made available 

through a ShareLinkTM file for voting ACIP Voting Members, Ex Officios, and Liaisons. She 

indicated that there would be two (2) oral public comment sessions, the first on June 22, 2022 at 

approximately 3:00 PM Eastern Time (ET) and the second on June 23, 2022 at approximately 

1:10 PM ET. To create a fair and more efficient process for requesting to make an oral 

comment, people interested in making a comment were asked to submit a request online in 

advance of the meeting. Priority is given to these advanced requests. Given that more 

individuals registered to make oral public comments than could be accommodated, selection 

was made randomly via a lottery. Speakers selected in the lottery for this meeting were notified 

in advance of the meeting. Individuals who were not selected and other individuals wishing to 

make written public comments may submit them through https://www.regulations.gov using 

Docket Number CDC-2022-0062. Further 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, CDC has issued limited 

COI waivers. Members who conduct vaccine clinical trials or serve on data safety monitoring 
ACIP Meeting Summary June 22-23, 2022

5 

boards (DSMBs) may present to the committee on matters related to those vaccines, but are 

prohibited from participating in committee votes. 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 

meeting.

Dr. Wharton also announced that applications and nominations were being solicited for 

candidates to fill upcoming vacancies on the ACIP. Detailed instructions for submission of 

names of potential candidates to serve as ACIP members are available on the ACIP website.

Applications for ACIP membership are due no later than August 15, 2022, for the 4-year term 

beginning July 2023. ACIP will be filling 6 positions at this time, including the Consumer

Representative position.

INFLUENZA VACCINE

Session Introduction

H. Keipp Talbot, MD (Chair, Influenza WG) introduced this session on behalf of the Influenza 

Workgroup (WG). She reported that recent WG discussion have focused on elements of the EtR 

Framework for influenza vaccination of persons ≥65 years of age and development of proposed 

recommendations for 2022-2023. The agenda for this session included preliminary estimates of 

2021-2022 seasonal influenza VE against medically attended influenza, the EtR Framework for 

influenza vaccination of persons ≥65 years of age, and proposed recommendations, and a vote.

Preliminary Estimates of 2021–2022 Seasonal Influenza VE against Medically Attended 

Influenza

Jessie Chung, MPH (CDC/NCIRD) presented preliminary estimates of 2021–2022 seasonal 

influenza VE against medically attended influenza. As a reminder, these are the 4 components 

of the 2021-2022 US influenza vaccines:

The results Ms. Chung shared came from the US Flu VE Network, which is comprised of the 

following 7 research sites: Kaiser Permanente Washington, Kaiser Permanente Southern 

California, Baylor Scott & White Health, Marshfield Clinic Research Institute, Vanderbilt 

University, University of Michigan, and University of Pittsburgh. These sites conduct active 

enrollment of patients seeking outpatient medical care for an acute respiratory illness (ARI) that 

includes a cough and/or fever.

This analysis was restricted to ambulatory patients >6 months of age with acute respiratory 

illness (ARI) with fever or cough ≤7 days in duration. Patients were enrolled October 4, 2021–

April 30, 2022. A test-neglect case-control study design was used that compared vaccination 
ACIP Meeting Summary June 22-23, 2022

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odds among influenza reverse transcriptase polymerase chain reaction (RT-PCR) positive 

cases and influenza RT-PCR negative controls. Persons who tested positive for SARS-CoV-2 

were excluded from this analysis. Vaccination status was defined as “receipt of at least one 

dose of any 2021–22 seasonal flu vaccine according to medical records, immunization 

registries, and/or self-report.” VE was calculated from logistic regression models adjusted

for study site, age, self-rated general health status, race/ethnicity, and month of illness onset.

The Flu VE Network enrolled over 6,000 persons in this timeframe, including 502 (7%) who 

tested positive for influenza and 2,046 (30%) who tested positive for SARS-CoV-2. There were 

15 flu/SARS-CoV-2 co-infections detected. Among the influenza positives, 94% were A/H3N2

viruses. All of the genetically characterized viruses belonged to Clade 3C.2a1b, Subclade 2a.2 

and no influenza B viruses were detected among these participants.

Overall, VE against influenza A viruses was 34%, with a statistically significant 95% confidence 

interval that ranged from 19% to 46%. VE against influenza A/H3N2 was 35%, with a 95% 

confidence interval that ranged from 19% to 47%. When broken down into 3 age groups (6 

months – 17 years, 18 – 49 years, ≥ 50 years), VE against A/H3N2 was highest in the pediatric 

age group, including persons 6 months – 17 years for whom VE was 44% (22 to 60) and was 

statistically significant. VE among adults 18 – 49 years was 27% (-3 to 48). It was not possible 

to calculate an adjusted VE estimate for adults ≥50 years of age due to the limited number of 

cases enrolled. Only 67 A/H3N2 cases were enrolled in this age group.

To summarize, the preliminary findings for the 2021-2022 US season indicate that vaccination 

reduced ARI due to A/H3N2 by 35% (95% CI: 19‒47). Almost all viruses sequenced nationally 

belong to Clade 3C.2a1b, Subclade 2a.2. Very low influenza prevalence was observed among 

all enrollees this season. The 2022-2023 Northern Hemisphere influenza vaccine will include 

updated reference virus for A/H3N2 (Clade 3C.2a1b, Subclade 2a.2), as well as an updated 

B/Victoria component (B/Austria/1359417/2021). 

Discussion Summary

Dr. Poehling requested a reminder the percent of persons who were both influenza-positive and 

COVID-19-positive and asked whether any differences were observed between those who had 

influenza only versus those who were co-infected.

Ms. Chung indicated that only 15 co-infections were identified. Given that there were so few coinfections, no comparisons were made.

Influenza Vaccines for Persons Aged ≥65 Years: EtR Framework

Lisa Grohskopf, MD, MPH (CDC/NCIRD) summarized the EtR Framework discussion by the 

Influenza Vaccines WG for the review of influenza vaccines for persons ≥65 years of age, 

following a brief review the background for this assessment. Persons ≥65 years of age are at 

increased risk of severe illness, hospitalization, and death due to influenza relative to younger 

age groups. This age group has been a target population for annual influenza vaccination since 

the early 1960s. However, influenza vaccines are often less effective for people in this age

group compared with younger populations. This table summarizes annual estimates of US

influenza VE from the CDC US Flu VE Network for the 2011-2012 through 2019-2020 seasons.
ACIP Meeting Summary June 22-23, 2022

7 

All of the influenza vaccines currently approved and available in the US with the single 

exception of the live-attenuated influenza vaccine (LAIV), are approved for persons ≥65 years of 

age. These include the following:









5 standard-dose, unadjuvanted inactivated influenza vaccines (SD-IIVs)

1 high-dose inactivated influenza vaccine (HD-IIV)

1 adjuvanted inactivated influenza vaccine (aIIV)

1 recombinant influenza vaccine (RIV)

ACIP has previously expressed no preferential recommendation for any specific influenza 

vaccine or vaccines for this age group. There were 3 influenza vaccines of specific interest for 

this review. The high-dose inactivated influenza vaccine currently available as Fluzone® HighDose Quadrivalent (HD-IIV4) was approved as a trivalent in 2009 for persons ≥65 years of age. 

It contains four times the hemagglutinin (HA) dose per virus compared with SD-IIVs (60 

μg vs. 15 μg). Initial approval was under the FDA Accelerated Approval pathway based on

superior immunogenicity to SD-IIV3. Subsequent approval under the traditional pathway 

occurred in 2014, following demonstration of superior efficacy to SD-IIV3 in a 2-season 

randomized trial among 32,000 participants ≥65 years of age. HD-IIV4, the currently available 

quadrivalent formulation, was approved in 2019 on the basis of non-inferior immunogenicity to 

HD-IIV3 and replaced HD-IIV3 for the 2020-2021 season.

The adjuvanted influenza vaccine, also an inactivated vaccine currently available as Fluad®

Quadrivalent (aIIV4), was approved in the US as a trivalent aIIV3 in 2016 for persons ≥65 years 

of age. This product had been in used previously in Europe for many years since as early as 

1997. It contains the adjuvant MF59 initially was approved under the Accelerated Approval 

pathway based upon non-inferior immunogenicity to unadjuvanted SD-IIV3. In a post-marketing 

efficacy study, the quadrivalent aIIV4 was compared with Tdap in a 2-season randomized trial 

among 6,700 persons ≥65 years of age. The primary efficacy endpoint for this study, prevention

of PCR-confirmed protocol-defined influenza-like illness (ILI) due to any influenza was not met.

It was noted that 88% of the antigenically characterized viruses from cases in the active arm 

were antigenically mismatched. Efficacy was noted against PCR-confirmed CDC- and World 

Health Organization (WHO)-defined ILI due to any virus. aIIV4 is approved under the

Accelerated Approval pathway and replaced aIIV3 for the 2021-22 season.
ACIP Meeting Summary June 22-23, 2022

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Flublok® Quadrivalent is somewhat different from the previous 2 vaccines in that it was not 

initially approved in the US for persons ≥65 years of age. Flublok® Quadrivalent initially was 

approved as a trivalent Flublok® RIV3 in 2013 for persons 18 through 49 years of age. This 

vaccine has 3 times the HA dose per virus compared with SD-IIVs. It is a recombinant HA and it 

has no viruses or eggs used in production. It was initially approved under the traditional pathway 

based upon efficacy demonstrated in a randomized placebo-controlled study among persons 18 

through 49 years of age. Subsequently, it was approved for persons ≥50 years of age in 2014 

under the Accelerated Approval pathway on the basis of immunogenicity studies among

persons in this age group. RIV4, the quadrivalent formulation, demonstrated efficacy relative to 

SD-IIV4 in a single-season randomized study conducted among about 8,600 persons ≥50 years 

of age. RIV3 and RIV4 gained traditional approval for ages 50 and older in 2017. RIV4 replaced

RIV3 for the 2018-2019 season. To recap, these 3 vaccines are all currently available as are the 

rest of the influenza vaccines that are available as quadrivalent formulations. As of this influenza 

season, trivalent influenza vaccines are no longer available. 

The Grading of Recommendation Assessment, Development and Evaluation (GRADE) 

summary for this review was presented during the February 2022 ACIP meeting. The question 

of focus was, “Do the relative benefits and harms of HD-IIV, aIIV, and RIIV as compared with 

one another and with other influenza vaccines favor the use of any one or more of these

vaccines over other age-appropriate influenza vaccines for persons ≥65 years of age?” Inherent 

in this question were 6 relevant comparisons, which included the following:













HD-IIV vs. SD-IIV

aIIV vs. SD-IIV

RIV vs. SD-IIV

HD-IIV vs. aIIV

HD-IIV vs. RIV

aIIV vs. RIV

One thing to note in this presentation going forward is that the terms “higher dose” and

“adjuvanted influenza vaccines” replace the collective term previously used in these discussions

to define collectively high dose adjuvant and recombinant vaccines, which was “enhanced

influenza vaccines.” The reason for this change is that while there is a precedence for the use of 

the term “enhanced influenza vaccines” in the literature, it does not have a strict definition and 

might lead to confusion as to what counts as such a vaccine, particularly as new vaccines

emerge going forward.

The population, intervention, comparators, outcomes (PICO) for this question were as follows.

The population of interest was adults ≥65 years of age. Interventions included higher dose, 

adjuvanted, or recombinant influenza vaccines (collectively higher dose or adjuvanted vaccines 

in trivalent or quadrivalent formulations). Comparators included SD-IIVs and higher dose and 

adjuvanted influenza vaccines, which were included in both the intervention and the comparator 

boxes because they could be compared with one another. Critical outcomes of interest included 

influenza illness, influenza-associated outpatient and emergency department (ED) visits, 

influenza-associated hospitalizations, and influenza-associated deaths—all due to any viral type

or subtype and defined by laboratory-confirmation, diagnostic codes, or clinical definitions.

Critical safety outcomes included any solicited systemic adverse event (AE) Grade 3 or higher 

and Guillain-Barré Syndrome (GBS). Important outcomes included any solicited injection-site 

AE Grade 3 or higher and any serious adverse event (SAE). 
ACIP Meeting Summary June 22-23, 2022

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With that background, Dr. Grohskopf summarized the WG’s discussion and considerations of 

the EtR Framework domain-by-domain, starting with the first domain of public health 

importance. In discussing the significance of influenza among persons ≥65 years of age, the 

WG reviewed influenza hospitalization and surveillance data, as well as an analysis by Rolfes et 

al1 that estimated the burden of influenza in the US by age group for the 2010-2011 through 

2015-2016 influenza seasons using data from routine influenza surveillance, outbreak

investigations, and survey data describing proportions of persons seeking healthcare. The 

highest burden of influenza hospitalizations and deaths was among persons ≥65 years of age, 

with estimated ranges of 87,000 to 521,000 hospitalizations, 3,000 to 17,000 excess pneumonia 

and influenza deaths, and 9,000 to 43,000 excess respiratory and circulatory deaths over this 6-

year study. The WG was unanimous in the view that influenza among older adults is a problem

of public health importance.

The next domain is benefits and harms. The systematic review and GRADE were previously

summarized in some detail in previous meetings. Most recently, GRADE was summarized 

during the February 2022 ACIP. This presentation focused primarily on the critical outcomes 

selected by the WG. For benefits those are prevention of influenza illness, influenza-associated 

outpatient/ED visits, influenza-associated hospitalizations, and influenza-associated deaths. For 

harms the critical outcomes were any solicited systemic AE of Grade 3 or higher and GBS.

In terms of the comparisons of higher dose and adjuvanted influenza vaccines with one another, 

there was only 1 randomized study that was relevant for all 3 comparisons (HD-IIV vs. aIIV, HDIIV vs. RIV, and aIIV vs. RIV). This was a very small study that included all 3 vaccines, with 

approximately 30 participants per group. This was primarily an immunogenicity study that 

reported influenza PCR-positive ILI as an exploratory outcome. Given the size and power of the 

study, no significant differences were observed for any of these outcomes. In each comparison, 

the quality of evidence was determined to be of very low certainty. The study was downgraded 

for risk of bias as it was an open-label study, as well as for imprecision. There were no other 

randomized studies for any of these 3 comparisons or studies that used laboratory-confirmed

influenza outcomes. 

The remainder of the studies retrieved for these comparisons were retrospective cohort studies,

including diagnostic code-defined outcomes. Since the last presentation of these data, following 

some additional discussion, the certainty results containing these data have been downgraded 

an additional step for risk of bias due to concerns over potential for residual confounding.

Therefore, some of the certainty levels are lower than in the February 2022 presentation. For 

the high-dose versus adjuvanted comparisons, neither vaccine was favored in retrospective 

cohort studies for the outcomes of influenza-associated outpatient/ED visits or influenzaassociated hospitalizations. Certainty was low. Downgrading for this was due to the outpatient 

studies, risk of bias, and inconsistency because 2 studies were performed during the same 

season that had substantially different estimates. For the hospitalization outcome, certainty was 

downgraded for risk of bias and imprecision. For the high-dose versus adjuvanted comparison 

that summarizes the retrospective cohort data, in the case of the estimates for high-dose versus 

recombinant and adjuvanted versus recombinant, there was evidence of benefit for the

recombinant vaccine for prevention of influenza-associated hospitalizations. Again, both favored

recombinant with low certainty. However, these results came from only 1 study performed over 

one influenza season.

1 Rolfes et al. Annual estimates of the burden of seasonal influenza in the United States. Influenza Other Respi Viruses 

2018;12:1232-137
ACIP Meeting Summary June 22-23, 2022

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Considering together the results among studies affording direct comparisons of benefit

outcomes among the higher-dose and adjuvanted vaccines, the WG felt that the evidence is 

insufficient currently to inform a decision for any one vaccine over the others. In the interest of 

time, the WG did not re-summarized the safety results that were presented in February 2022. 

However, it also was reassuring that among studies providing safety data for these 

comparisons, which included one randomized controlled trial (RCT) comparing high-dose

versus adjuvanted vaccine for safety outcomes, there were no results favoring any vaccine.

Overall certainty for these outcomes was low, primarily due to imprecision stemming from low 

event counts and often small sample sizes.

The WG then discussed comparisons of each of the higher dose or adjuvanted vaccines

with standard dose unadjuvanted vaccines. For high-dose versus standard dose for influenza 

illness, there was 1 large, 2-season randomized trial that noted a relative risk of 0.76 translating

into a relative VE of about 24%, favoring high-dose compared with standard dose. This was 

high-certainty evidence. For influenza-associated outpatient and ER visits, there was evidence 

favoring high-dose with a relative risk of 0.7 from a retrospective of cohort study covering 4 

seasons, with low certainty and that was downgraded for risk of bias. For hospitalizations, there 

was evidence of relative effectiveness favoring high-dose with a relative risk of 0.79 from a 

cluster-randomized trial conducted within a network of 823 nursing homes during a single

season. This was judged to be moderate-quality evidence. Though it is a cluster-randomized 

trial, it was reassuring that the risk estimate, and by extension, the relative VE was similar to 

that obtained in the large, randomized efficacy trial. There also was evidence from observational 

studies favoring high-dose over standard dose for influenza-associated deaths, with an effect

estimate of 0.67, which was low-certainty evidence.

Moving to a comparison of adjuvanted versus standard dose for the benefits outcomes of

efficacy and effectiveness, no RCTs were retrieved that used laboratory-confirmed influenza

outcomes. One RCT, primarily a safety study, examined occurrence of influenza identified 

strictly by a symptomatic definition that saw no difference. Studies spoke to the outcome of

influenza-associated outpatient visits, but evidence here was variable. There were 2 

retrospective cohort studies identified that examined code-defined outcomes that were

conducted in the same season. No effect was seen in the pooled estimate. This evidence had to 

be downgraded for risk of bias and inconsistency because the 2 estimates from the same

season had substantially different results. There were 2 smaller observational studies that, 

combined, favored aIIV with a risk estimate of 0.64. For hospitalizations, there was evidence

favoring aIIV with a risk ratio of 0.79 and moderate certainty from a cluster-randomized trial 

using diagnostic code to find pneumonia and influenza outcomes. This trial was of similar

design and was conducted in a similar nursing home network to the cluster-randomized trial 

described earlier for the high-dose vaccine. There also was evidence favoring aIIV from 3 

retrospective cohort studies using code-defined hospitalizations and from 2 smaller

observational studies. These estimates for hospitalizations were considered to be low-certainty 

evidence.

For recombinant versus standard dose. For this comparison, and for recombinant vaccine data 

in general, there are fewer studies. For influenza illness, there were 2 RCTs, a smaller one 

dating from about 2010 comparing RIV3 with SD-IIV3 and a more recent larger trial comparing 

RIV4 and SD-IIV4. This was high-certainty evidence, but the risk estimate was equivocal. Of 

note, the more recent larger study drives most of the results in the meta-analysis for this 

particular comparison and the total study population was ≥50 years of age. For the study

population as a whole, there was a reduction in PCR-confirmed influenza with RIV4 compared 

with SD-IIV4 for a relative risk of about 0.7. PCR-confirmed influenza was the primary outcome 
ACIP Meeting Summary June 22-23, 2022

11

defined by the study. However, no reduction in risk was seen for persons ≥65 years of age in a 

sub-analysis. However, the WG, felt that this work was nonetheless important because of the 

reduction seen for persons ≥50 years of age and because a reduction in risk for some other 

outcomes, including culture-confirmed influenza, was seen in the subset of persons ≥65 years 

of age. There also was evidence of benefit against hospitalization from a large retrospective 

cohort study among Medicare beneficiaries using diagnostic code of defined outcomes, which 

yielded a risk estimate of 0.83. While this favored recombinant vaccine, it was judged lowcertainty evidence.

To summarize the harms outcomes for each vaccine of interest versus standard dose 

unadjuvanted vaccine, neither vaccine was favored for any of the 2 critical safety outcomes 

across any of the 3 comparisons. The overall quality of these estimates was low to very low.

This primarily was due to small event counts and often small sample sizes in these studies,

as well as the relative rarity of GBS.

In terms of the WG’s considerations, it was recognized that among the 3 higher dose and 

adjuvanted vaccines, the most data are available to support high-dose, which had some 

evidence favoring its benefits for all 4 of the selected critical efficacy and effectiveness

outcomes. This includes the very large 2-season randomized trial that noted a relative VE of 

24% for high-dose versus standard dose vaccine. However, considering data for the various 

outcomes across the vaccine comparisons, it also was noted that the most data were available 

across the board for hospitalizations. While all of the efficacy outcomes were regarded as 

critical, hospitalizations are of particular interest for being a relatively common and also severe 

outcome for this age group. For this outcome, there is evidence supporting each of the 3 higher 

dose or adjuvanted influenza vaccines over standard dose vaccines. These estimates were 

considered moderate certainty for high-dose and adjuvanted vaccines. In each case, this was 

driven by findings from large cluster-randomized trials. Evidence was of low certainty for 

hospitalization outcomes for the recombinant vaccine. In the discussions of these factors in 

looking over these findings, the WG also noted that relative VE varies from season-to-season. 

Therefore, the benefits of one vaccine compared with one another are not necessarily static.

Relative benefit might not be seen for any given vaccine combination or one vaccine over 

another being better in every season. For some seasons in multi-season studies, no benefit was 

seen for the higher dose or adjuvanted vaccine over standard dose vaccines. It seems that what 

performs better in one season might not in another.

With regard to safety, no concerns were identified in the findings for the critical safety outcomes 

from the WG’s review. There was discussion concerning the overall level of certainty for these 

outcomes, which was low to very low depending upon the comparison and the outcome. The 

WG was concerned that it is important to emphasize that this is due to a low level of certainty in 

the evidence, largely due to imprecision of the effect estimates. This is not uncommon with

safety studies in general due to small event counts and small sample sizes for some studies.

The WG felt strongly that it should be emphasized that this is not to be interpreted as a safety 

concern.

In terms of the overall certainty of the evidence for the critical outcomes, the level of certainty 

was low for each vaccine comparison for benefits overall. For harms overall, certainty was low 

for high-dose versus standard dose and adjuvanted versus standard dose and very low for

recombinant versus standard dose. Approximately half of the WG indicated that the desired 

anticipated effects are they are moderate, but a substantial minority thought that this varies due 

to the variability of influenza VE from season-to-season. The majority of the WG thought that the 

desirable anticipated effects are minimal. Considering all of these findings and factors, the 
ACIP Meeting Summary June 22-23, 2022

12

sentiment of the majority of the WG was that the balance of benefits and harms favors the

intervention.

Moving to the domain of values, the WG found no published evidence reflecting values

of US seniors concerning higher dose and adjuvanted vaccine specifically or the relative 

importance of the selected outcomes. However, 1 analysis was identified that might speak to 

values. There was a recent Centers for Medicare and Medicaid (CMS) analysis of their data for 

Medicare beneficiaries that suggests that the majority of community-dwelling Medicare

beneficiaries ≥65 of age already have received 1 of these 3 vaccines in recent seasons. This 

suggests that some seek out these vaccines specifically. However, it also was noted that 

provider choices and recommendations also are important in determining what vaccines are 

received. The impressions of the WG regarding the questions for this domain reflected some 

degree of uncertainty. The majority of WG members indicated that they thought the target

population probably feels that the desirable effects of a new recommendation are large relative 

to the undesirable effects, and that there probably is not important uncertainty or variability in 

how people value the main outcomes evaluated.

Regarding the domain of acceptability, no literature was found reflecting the acceptability of the 

vaccines of interest among US seniors. A number of studies and papers were found that 

reflected questions, such as willingness to pay for specific vaccines over others. However, most 

of these were not US papers and do not reflect US payment for influenza vaccines or the US

population. However, the WG felt that some indirect evidence of the acceptability of high-dose, 

adjuvanted, and recombinant influenza vaccines among persons ≥65 years of age can be seen 

in recent analyses of VE among Medicare beneficiaries, which suggests that most people ≥65

years of age already have received a higher dose or an adjuvanted vaccine in recent seasons.2 

of them are reflected, are in the tables that you saw earlier. There were some exclusions in the 

study population. For example, one of the more significant ones is that persons residing in 

nursing homes at the time of vaccine administration were excluded. In addition, not all

vaccinations are recorded in the Medicare database. Therefore, it cannot be said that the study 

populations for these papers includes the entire universe of Medicare beneficiaries. The analytic 

datasets contained 12 to 13 million people each season. For each season, the majority of 

individuals in this dataset had received 1 of 3 vaccines (HD-IIV3, aIIV3, or RIV4), with

approximately 81% having received one of these vaccines in the 2019-2020 data. While this is 

not direct evidence of acceptability to all key stakeholders, the current degree of uptake 

suggests at least some current level of acceptability to vaccine providers and recipients. The 

majority of WG members felt that the intervention is acceptable to key stakeholders. 

In terms of the domain of resource use, there are multiple published economic evaluations of 

high-dose and adjuvanted vaccines compared with standard vaccines. Given the possibility of a 

recommendation for more than 1 of these vaccines over SD-IIV, an economic analysis was 

conducted. For this section, Dr. Grohskopf presented an analysis by Dr. Fangjun Zhou

of the CDC Immunization Services Division (ISD). The objective of this work was to conduct a 

cost-effectiveness analysis of use of higher dose and adjuvanted influenza vaccines (HD-IIV, 

RIV, and aIIV) among adults ≥65 years of age in the US compared with standard dose 

unadjuvanted influenza vaccines from the societal perspective. The assumptions for the base 

case were drawn from the averages of the 2017-2018 through 2019-2020 influenza seasons for 

2 a) Izurieta HS, et al. Relative Effectiveness of Cell-Cultured and Egg-Based Influenza Vaccines Among Elderly Persons in the 

United States, 2017-2018. J Infect Dis. 2019 Sep 13;220(8):1255-64; b) Izurieta HS, et al. Relative Effectiveness of Influenza 

Vaccines Among the United States Elderly, 2018-2019. J Infect Dis. 2020 Jun 29;222(2):278-87; and c) Izurieta HS, et al. 

Comparative Effectiveness of Influenza Vaccines Among US Medicare Beneficiaries Ages 65 Years and Older During the 2019-

2020 Season. Clin Infect Dis. 2021 Dec 6;73(11):e4251-e9.
ACIP Meeting Summary June 22-23, 2022

13

disease burden, vaccination coverage, and VE. The basis for the selection of these 3 seasons 

was that they were some of the few seasons in which there were relative VE estimates for all 

relevant vaccine comparisons that are available within the context of the same study. These

estimates came from the Izurieta et al studies, which estimated relative VE of the various

vaccine comparisons against pneumonia and influenza diagnostic-coded hospital encounters. 

That is, inpatient stays and ED visits combined. These particular estimates from these papers

were used for these assumptions. Using the base-case assumptions, the incremental costeffectiveness ratios in dollars per quality-adjusted life year (QALY) were $52,000 for high-dose 

versus standard dose, $60,100 for adjuvanted versus standard dose, and were cost-saving for 

recombinant versus standard dose. Average cost-effectiveness ratios were $6,600 for high-

,dose versus no vaccine, $7,600 for adjuvanted versus no vaccine, and were cost-saving for 

both the recombinant versus no vaccine and standard dose versus no vaccine.

In terms of the estimated numbers of health outcomes for each vaccine type under the base 

case set of assumptions, each vaccine (HD-IIV, aIIV, and RIV) was estimated to result in fewer 

illnesses, hospitalizations, and deaths. Looking across the 3 vaccines, approximately 2,000 

additional deaths would be prevented with enhanced influenza vaccines. This assumes current 

use of higher dose and adjuvanted vaccines of 80% in the population ≥65 years of age. It was 

further estimated that an additional approximately 400 deaths might be prevented if 100% of 

these vaccinated adults received one of the higher dose or adjuvanted vaccines. To get an idea 

of the potential impact of different scenarios of relative VE and influenza burden on the

incremental cost-effectiveness ratios, the 2017-2018, 2018-2019, and 2019-2020 estimates

for VE were applied to the disease burden data from 10 consecutive influenza seasons from 

2010-2011 through 2019-2020, with the results shown in this table:

To summarize the results from this table into a more visual format, the following incremental 

cost-effectiveness curve was constructed: 
ACIP Meeting Summary June 22-23, 2022

14

This illustrates that 20% of the scenarios were cost-saving, 50% cost less than $43,000 per 

QALY gained, 75% of scenarios cost less than $85,000 per QALY gained, and 95% cost less 

than $195,000 per QALY gained. Incremental cost-effectiveness ratios for higher dose and 

adjuvanted vaccines versus standard vaccines vary considerably based upon underlying VE 

and influenza season severity. 

This analysis has some limitations. This modeling work indicates substantial uncertainly in

estimates of value due to multiple product comparisons and the inherent variability of influenza 

burden and VE from season-to-season. As noted earlier, the VE assumptions were derived

from estimates obtained in a retrospective cohort study of vaccine for the prevention of 

influenza-associated hospital encounters. These estimates are not from randomized trials,

in part because randomized trials are too few in number to be able to find sufficient assumptions 

for this model. In addition, it is difficult to find estimates for all of the relevant outcomes during 

the same influenza season. It should also be noted that VE might differ for different outcomes, 

even for the same vaccine comparison within the same season. That is to say, VE for 

hospitalizations/hospital encounters and ED visits will not necessarily be the same as VE for 

clinical illness or other outcomes. On the question of whether the intervention is a reasonable

and efficient allocation of resources, the WG acknowledged that given the variabilities

associated with influenza burden and VE, cost-effectiveness of higher dose or adjuvanted

vaccines will vary from season-to-season. However, a majority of the WG felt overall that a 

recommendation to use higher dose and adjuvanted influenza vaccines over standard dose 

vaccine would be a reasonable and efficient allocation of resources. A minority of the WG

voiced that it probably would be a reasonable and efficient allocation of resources and a smaller 

minority indicated that this would vary.

In terms of the domain of equity, racial and ethnic disparities in overall influenza vaccine 

coverage and in rates of severe influenza illness have been documented in several studies. 

Mahmud et al (2021) examined receipt of high-dose vaccine versus all other seasonal influenza 

vaccines combined as a group among Medicare beneficiaries ≥65 years of age during the 2015-

2016 influenza season. In addition to disparities in receipt of any seasonal influenza vaccine, a 

finding that has borne out in many other papers, the authors noted disparities in the use of highdose vaccine compared with standard-dose vaccine by race and ethnicity. Compared with White 

recipients, those of Black or Asian race and those of Hispanic ethnicity were significantly less 

like to receive the higher-dose vaccine. In discussing the potential impact of a new

recommendation on equity, the WG recognized that impact depends upon underlying causes of 
ACIP Meeting Summary June 22-23, 2022

15

the differences in receipt of these vaccines. Potential factors include (but are not limited to) cost, 

differences in practice settings, and differences in linkage to care. It also was noted that the

Mahmud study occurred during the 2015-2016 season at which time, aIIV had not yet been 

introduced in the US, RIV was relatively new to the market, and there were somewhat fewer 

options for this age group. Nonetheless, given what is known about persisting disparities in 

influenza vaccination coverage in the population as a whole, inequities in this age group remain 

a concern. While it is not possible to know whether a recommendation for higher dose or 

adjuvanted vaccines would positively impact equity, the WG’s sense was that there is not a 

basis to predict negative impact. On the question of equity, the majority of the WG expressed 

the view that a new recommendation probably would increase equity. A smaller proportion 

expressed that the intervention would increase equity or that it would probably have no impact.

None indicated that equity would be reduced or probably reduced.

In the WG’s discussion of the domain of feasibility a point that was thought to speak to the issue 

of feasibility was, it was observed that the analyses of CMS data suggest most communitydwelling CMS beneficiaries ≥65 years of age already have received a higher dose or

adjuvanted influenza vaccine during recent seasons (2017-2018 through 2019-2020). While 

there were differences in the proportions who received high-dose versus adjuvanted versus 

recombinant relative to one another and there was some shifting in those proportions over the 3 

seasons examined, these vaccines already appear to be in established use in this population.

From a reimbursement perspective, CMS already reimburses for all influenza vaccines that are 

approved for this age group. There are some differences in the reimbursement rates. HD-IIV, 

RIV, and aIIV are reimbursed at a higher rate than SD-IIVs as of 2021-2022 at approximately 

$65 to $67 per dose for the higher dose and adjuvanted vaccines versus approximately $20 to 

$28 for single dose presentations of SD-IIVs. There is somewhat more spread in the figure for 

the standard dose vaccines primarily because the reimbursement for Flucelvax® Quadrivalent, 

the cell-based vaccine, is somewhat higher than the remaining vaccines that are egg-based.

Higher dose and adjuvanted influenza vaccines are also similar in administration and storage to 

other intramuscular influenza vaccines. Overall, the WG felt that an intervention recommending 

higher dose or adjuvanted influenza vaccines would be feasible to implement.

To summarize the WG’s overall conclusion in considering all of the EtR domains and with the 

intervention being higher dose or adjuvanted vaccines over SD-IIVs for persons ≥65 years of 

age, the breakdown for the domains follows. The WG agreed that influenza among older adults

is a problem of public health importance. The substantiality of desirable and anticipated effects

of an intervention was felt to be moderate on average, but variable. The substantiality of the 

undesirable anticipated effects was felt to be minimal. The balance of the desirable and

undesirable effects was felt to favor the intervention. Overall, the certainly of the evidence for 

the higher dose and adjuvanted vaccines versus the standard vaccines was low for the critical 

efficacy and effective outcomes. The breakdown for the critical safety outcomes was low for 

high-dose and adjuvanted and very low for recombinant. The low to very low assignments of

certainty were primarily due to low precession of the estimates gathered from studies that often

had small event counts and small sample sizes. The WG reinforced that overall, these vaccines 

have been demonstrated to be safe. While there were few specific data to discuss relevant to 

values, the WG felt that the target population probably feels that the desirable effects outweigh 

the undesirable effects and that there is probably no important uncertainty or variability in how 

people value the main outcomes. The WG felt that the intervention is likely to be acceptable to 

key stakeholders and a reasonable and efficient use of resources. With regard to equity, most 

felt that the intervention probably would increase equity, and no one responded that it would 

decrease equity. The intervention was felt to be feasible to implement.
ACIP Meeting Summary June 22-23, 2022

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In considering the elements of the EtR previously discussed with regard to overall balance of 

consequences inherent in a new recommendation, the majority of the WG felt that desirable 

consequences clearly outweigh undesirable consequences in most settings. A somewhat lesser 

proportion responded that they thought that desirable consequences probably outweigh 

undesirable consequences in most settings. None of the other options were selected. On the 

question of whether there is sufficient evidence to move forward with the recommendation, the 

majority of WG members responded “yes.” The WG discussed several potential

recommendations. The first option was to make no change in the recommendation. That is to 

say that any age-appropriate influenza vaccine is recommended for persons ≥65 years of age. 

The second option was that that high-dose vaccine is recommended when available and that, if 

not, any age-appropriate vaccine can be used. The third option was that high-dose vaccine is 

recommended when available. If not, then either adjuvanted or recombinant vaccine may be 

used, if available. If none of these 3 options is available, then any age-appropriate vaccine may 

be used. The fourth option was that that high-dose adjuvanted or recombinant vaccines are

recommended when available. If none of these 3 vaccines is available, any age-appropriate 

vaccine may be used. The majority of the WG opted for the fourth option.

A number of points emerged during the WG’s discussion of the EtR and of the potential

recommendation language just summarized, some of which concern the evidence base. It was 

acknowledged that randomized trials, ideally against laboratory-confirmed outcomes, are the 

most desirable evidence. However, such trials are few in number, are very resource-intensive to 

implement, and are not easily executed over repeated seasons. Given the variability of influenza 

seasons and of VE, it is difficult to assume that findings from a few seasons will generalize to all 

or most seasons. In this case, there are only 2 randomized efficacy trials comparing higher-dose 

and adjuvanted vaccines versus-standard dose vaccines with laboratory-confirmed outcomes—

the 2-season trial for high-dose versus standard dose and the 1-season trial for recombinant 

versus standard dose. There were no comparable randomized trials comparing adjuvanted

standard dose. The trial mentioned at the start of this presentation of aIIV versus Tdap was not 

part of the GRADE analysis in this review because the primary focus was on studies providing 

estimates of relative VE of influenza vaccines compared with one another. As noted, this study 

did not demonstrate efficacy for its primary outcome. However, the majority of antigenically

characterized viruses from that study were due to antigenically drifted viruses. This

demonstrates another difficulty with randomized trials of influenza vaccines. If the study is 

performed in what turns out it be a season of meaningful mismatch between vaccines and the 

predominant viruses in circulation, it might be difficult or impossible to draw conclusions either 

way about efficacy from the work of that season. An analogous, although more extreme

example of this, occurred with an earlier trial of high-dose vaccine versus standard-dose

vaccine, which occurred during what would become the 2009 H1N1 pandemic. In this study, no 

cases occurred to viruses antigenically matched with vaccine viruses due to the widespread

circulation of the pandemic virus, which essentially replaced the other viruses in circulation for 

that season.

While randomized trials are critical from a practical standpoint, decisions regarding potential

preferential recommendations for influenza vaccines might need to draw from observational 

studies and not be restricted to RCTs, while acknowledging the limitations of the observational 

studies in order to gain perspective on performance across seasons. It was acknowledged that 

the most data for the most outcomes are available to support the high-dose vaccine. However, it 

also was noted that while a single randomized trial of RIV4 versus IIV4 did not demonstrate 

benefit for the primary outcome for persons ≥65 years of age, it did demonstrate benefit for 

some other outcomes in this age subgroup of interest and also for the population as a whole for

persons ≥50 years of age. It also was noted that there is evidence to support adjuvanted
ACIP Meeting Summary June 22-23, 2022

17

vaccine from a cluster-randomized study and several observational studies. Another point was 

raised that a recommendation for a single vaccine over all others might lead to confusion if that 

vaccine does not demonstrate consistent benefit across future seasons. Conversely, it was felt 

that a recommendation for any of the 3 vaccines provides a balance of science and practicality 

given what is known about the variability of influenza seasons and VE. 

As noted earlier, there are fewer data comparing HD-IIV, aIIV, and RIV with one another. 

Among the available studies, the most provided data for the high-dose vaccine versus 

adjuvanted vaccine comparison. In these 3 comparisons as a whole, the only relative benefit 

was seen for the recombinant vaccine versus adjuvanted vaccine and the recombinant vaccine

versus high-dose vaccine. However, these 2 outcomes were based on a single study from a 

single influenza season. Overall, current evidence was felt to be insufficient to recommend one 

vaccine over the others. However, it also is likely that there will be more comparative data to 

examine in the near-term, possibly with the current quadrivalent formulations of the high-dose

and the adjuvanted vaccines for which the WG did not have any data to use in this review.

Other points spoke to feasibility and acceptability issues. For example, a recommendation for 1 

of 3 vaccines, when available, provides flexibility for providers. For example, for those who care 

for adults across an age spectrum, stocking RIV might be more practical since it is approved for 

persons ≥18 years of age and not only for persons ≥65 years of age. Another point raised was 

that this approach minimizes some of the risk associated with the recommendation for 1 vaccine 

above all others. For example, if there are unexpected delays in vaccine availability or 

manufacturing problems. 

Discussion Summary

Referring to Slide 18, Dr. Poehling requested additional details about what was meant by saying 

that they “favor the high-dose” and “favor aIIV” and “favor RIV.”

Dr. Grohskopf indicated that one of the issues the WG noticed in looking across studies, since

they had a sizable amount of retrospective cohort data in this canon they retrieved through the 

literature search, was that the estimates for outpatient and ED visits were somewhat more

inconsistent than hospitalizations. It is difficult to know exactly where that is coming from. One 

hypothesis the WG discussed is the possibility that since these are diagnostic code-based 

outcome definitions, the majority of them used ICD-9 pneumonia and influenza codes. Some of 

them were more restrictive and used only influenza codes. Someone might be more likely to get 

assigned that diagnosis on their coding sheet if they had been admitted to the hospital and

gotten the test as opposed to being seen as an outpatient or in the ED. The WG did not always 

see benefit in outpatient versus ED studies. In the particular case for the 4 retrospective cohort

studies combined, the WG noted that there are a lot of differences in the US Flu VE Network 

data in terms of VE versus in this kind of data from a retrospective cohort study of CMS data. 

The US Flu VE data have laboratory confirmation whereas the retrospective cohort data are by 

and large all code-based outcome definitions. The sample sizes for the US Flu VE Network are 

far smaller, in the thousands, as opposed to in the millions with the CMS analyses. Even if 

looking at data from the same season, it might not be possible to draw a lot of parallels. Another 

thing to consider with the Flu VE Network data, which has occurred over time, is that the

proportion of people who are receiving the high-dose vaccine in that network has increased 

since high-dose was introduced. This has increased considerably since the 2014-2015 season, 

along with a lower proportion of recombinant and adjuvanted use. Therefore, it is difficult to 

draw parallels between them. The end goal is to assess the same thing, which is VE, but the 

studies are measuring in different ways on different populations than the US Flu VE Network 
ACIP Meeting Summary June 22-23, 2022

18

population, particularly with the number of persons ≥65 years of age being much smaller than in 

a Medicare database.

Dr. Poehling requested additional information regarding aIIV and RIV comparison.

Dr. Grohskopf responded that there were fewer studies overall for this comparison. There was 

some variability with outpatient and ED depending on the study type. It was interesting that the 

2 retrospective cohort studies for adjuvanted versus standard dose. Looking at each of them

individually, they had results suggesting efficacy, but one favored one vaccine and not the other.

While there was some variability, there were relatively tight intervals. One of the reasons there 

are fewer data for outpatients than hospitalizations is that in the Izurieta group’s large 3-season 

analyses, the outpatient outcome were assessed for the first season, 2017-2018, and not for the 

2018-2019 and 2019-2020 seasons.

Dr. Daley asked how many of these studies were industry-funded and whether that was

discussed during the WG’s consideration of the body of the evidence. 

Dr. Grohskopf said that while she did not recall the exact number, the large 2-season RCT for 

the high-dose versus standard dose that had 32,000 people was an industry study. The

comparison study for the recombinant versus standard dose, the single-season study, also was

an industry study. She thought the RCT for adjuvanted versus standard dose was an industry 

study, which was not as helpful from an efficacy point of view because the outcome used was 

just a symptom-based influenza definition and it was mostly a safety study. Among the

observational studies, the large CMS database studies were US Government (USG) work. 

Some of the large retrospective cohort studies were funded either by manufacturers or had 

industry authors.

Dr. Daley asked what could be done to ensure that health inequality is not exacerbated by this 

recommendation. Perhaps there are settings in communities of color or in disadvantaged

geographic areas in which only standard dose is offered. There also may be awareness issues 

among persons ≥65 years of age who are seeking vaccine but do not know that there is a highdose or adjuvanted vaccine recommended for them.

Dr. Grohskopf acknowledged the importance of ensuring that health inequity is not exacerbated. 

An effort is being made to get a better sense of what makes these situations different

from other situations and why these things are happening. No having good linkage to care or a 

stable relationship with a healthcare provider (HCP) or a group of providers could be a factor. 

One of the strongest determining factors for getting an influenza vaccine is a trusted provider 

making a recommendation for it. There probably also are logistical issues. For instance, some 

clinical settings may not be sufficiently staffed or may not have good connections with other 

clinical groups to be able to efficiently handle multiple types of influenza vaccines—particularly if 

they serve smaller populations and need to stock vaccine that can be used for a broader range 

of the patients under their care. It is important to get a better sense of the root causes, which 

may be multiple.

Dr. Sanchez agree with the fourth possible recommendation that was made by the WG favoring 

HD-IIV4, aIIV4, or RIV4. He emphasized the importance of education for the public and 

providers.
ACIP Meeting Summary June 22-23, 2022

19

Dr. Long said that it was amazing that there is a vaccine that is recommended for the entire US

population, but for which the efficacy for influenza-like disease is quite low. These are mucosal 

infections with the inflammatory signatures. Because the virus changes so much, better efficacy 

would be beneficial. But maybe in future they should give up what they cannot have, a lot of 

control of simple disease, and focus more on hospitalizations and death. This intervention would 

be estimated to save an additional 2,000 deaths per year for persons ≥65 years of age, which is 

truly remarkable and cost-saving. She thinks a recommendation is very important because even 

in healthcare organizations, healthcare workers are aging. A recommendation would help to 

ensure that the most potent vaccines are available for this age group.

Dr. Talbot noted that it is much easier for practices to stock 1 vaccine product and give it to 

everyone, so many clinics probably have done that because it is much easier. This also has

created a disparity. Moving to a recommendation that an older adult should get a relatively 

better vaccine would change that. It would then become a priority to identify patients ≥65 years 

of age and give them the correct vaccine. She thinks such a recommendation would help to 

reduce current disparities.

Dr. Goldman (ACP) asked whether in the 2015 study that looked at equity, the data were 

subdivided for Medicare Advantage plans (Part C) versus straight Medicare. One of the quirks

of vaccine reimbursement is that certain vaccines like influenza, pneumonia, and hepatitis B are

covered under Medicare Part B. Others are covered under the drug plan, which in some cases, 

especially with the full-risk plans, may prevent physicians from being able to vaccinate in their 

office. This may further decrease access, availability, and equity. He asked if the WG 

considered this in the nuances of how to increase equity, especially allowing physicians to be 

able to administer certain vaccines in their offices.

Dr. Grohskopf indicated that the Izurieta analyses and the other analyses from that group that 

is out of FDA excluded Medicare Advantage, Part C, from the analyses.

Dr. Long said she was getting more confused as they went along with so many

recommendations. While the recommendation was straightforward, it also had embedded in it

that if one of these vaccines is not available, the standard vaccine should be given. She would 

rather say that high-dose or adjuvanted vaccines should be made available for people ≥65

years of age. If they want to save those extra 2,000 lives, they want to be sure that all doctors

understand that they should be giving these vaccines preferentially. The way the 

recommendation read seemed too passive.

Dr. Lee requested that Dr. Long raise this question again during the vote session.

Dr. Fryhofer (AMA) said that speaking as a practicing physician who administers influenza

vaccines in her office and orders influenza vaccines for her office generally in February each 

year, they need to make sure that they do not keep people in the current influenza season from 

being vaccinated. If the ACIP decided to vote on this recommendation, it likely would affect the 

supplies physicians have in their offices. She requested that the committee consider this in 

terms of making this recommendation.

Dr. Poehling asked whether the percentage is known of persons ≥65 years of age who are

vaccinated in a pharmacy versus a physician office. She also emphasized that as they are 

thinking about adult recommendations, it would be helpful to make sure there is a universal 

registry so that there is clear communication between practices and pharmacies.
ACIP Meeting Summary June 22-23, 2022

20

Dr. Grohskopf said that while she was not certain of the exact answer to that, vaccination in 

pharmacies has been increasing over the last number of years and is fairly commonplace.

Before the vote, they can seek additional information about the exact proportion to report back 

to the ACIP. Related to that is that it does seem that these vaccines are readily available in 

retail vaccination settings.

Dr. Lee commended and expressed appreciation for the WG, under the leadership of Drs. 

Talbot and Grohskopf, for synthesizing this tremendous amount of data so succinctly and 

efficiently. The literature is vast and variable, and it takes a lot of work to get it into a form that 

makes it easier for ACIP to deliberate on. As they learned from the COVID-19 pandemic, 

pharmacy partners have been incredibly helpful in ensuring that they are a key part of the 

delivery system. That has been longstanding for influenza vaccines in addition to physician 

offices who have done a huge amount of vaccine delivery. She agreed that it would be

incredibly helpful to have information about what proportion of individuals, by age group, receive 

vaccines in pharmacies versus offices more broadly and specific to influenza vaccine and what 

products are available where. In terms of whether regional or local variability and availability 

could impact some communities more adversely than others, if pharmacies are a predominant 

delivery system in certain communities for receiving influenza vaccine, that would be very 

helpful. As they look ahead about what can be done to reduce disparities, having that 

information would be helpful. She imagined that at the state and local levels, partner with their 

colleagues in the community could help to ensure that the gap is being closed from an 

implementation standpoint. She emphasized that education, community outreach, and 

sustaining the relationships built over the course of COVID-19 continue to be key. Resources

are dwindling again and all of the efforts made to engage community partners have been critical

for the COVID-19 response and in reducing disparities. She worries that as attention and 

funding fade, there will be important missed opportunities to continue to address disparities in 

health equity. While Dr. Lee recognized that this is not necessarily an ACIP- or CDC-only issue, 

federal funding is important to all vaccines in terms of preventive health issues. The

recommendation proposed made sense in the context of the cost-effectiveness analysis, but 

she asked about the difference in the actual cost per dose of these vaccines. In terms of

additional information, it would be helpful to understand what the vaccine safety monitoring 

plans would be going forward.

Dr. Grohskopf indicated that finding out the average retail price of these vaccines is generally 

fairly tricky. The WG was not successful in determining the wholesale price. Their understanding

was that the prices for vaccines can vary somewhat depending upon the purchasing power of 

the purchaser, how much they are buying, and what price can be negotiated. The analysis that 

she summarized used the CMS reimbursement rates cost assumptions. For the 3 vaccines in 

question, this was fairly similar at approximately $65 to $66 each versus a single-dose

presentation of the standard vaccines. They used single-dose presentation for comparison

mainly because there are no multi-dose presentations for the higher dose and adjuvanted 

vaccines. They are all prefilled syringes and are roughly $20 to $21 except the cell-culture 

vaccine, which is a little more expensive. There was some discussion about this with CDC’s 

economics group, and they typically used those numbers rather than a wholesale price for these 

analyses. For the second question regarding future safety monitoring, certain safety events are 

routinely monitored for in the VSD. She would anticipate that to continue, but deferred to

colleagues in the Immunization Safety Office (ISO) for more details.
ACIP Meeting Summary June 22-23, 2022

21

Dr. Goldman (ACP) pointed out as a private practice physician who gives all vaccines in his

office, including influenza vaccines, that they make sure not to neglect or forget about the

physicians who patients trust the most to advise them and how the system is being shifted to 

take vaccines out of physicians’ offices. Reimbursement issues, keeping the door open, and 

systems are making it increasingly difficult for practicing physicians to administer vaccines. He 

stressed that he meant no disparagement to his colleagues in the pharmacy sector who have 

been incredibly helpful during the COVID-19 pandemic and in their assistance with getting

outreach to various patients, but they cannot forget the physicians who also are vaccinating. He 

has patients get 2 or 3 doses of influenza vaccine at a pharmacy within the same 2-month

period because they are not using the registry and communicating with the physician offices.

The importance of partnership collaboration must be emphasized. Physicians are the leaders of 

the healthcare team and need to be included in the vaccination efforts.

Dr. Lett pointed out that some of the other QIV vaccines are less expensive than the 3 preferred 

vaccines being discussed. She has heard from some AIM colleagues that they are concerned

that some systems may not be making the higher-priced vaccines available. She wondered 

what kind of language could be used in terms of the vote and final recommendation to ensure 

that systems make the preferential vaccines available as well.

Dr. Grohskopf indicated that there was some discussion among the WG members about that. 

On the one hand, all of these vaccines are reimbursable under Medicare for those who are 

eligible. It does require spending more on the front end to purchase the vaccines and she 

imagined that being reimbursed for them requires actually having administered them. Every 

year, many doses of influenza vaccine are discarded in general. The hope is that if there is a 

recommendation and there is more public awareness, these vaccines would be recommended

more to patients and potentially would be more beneficial in terms of leading to more people

getting vaccinated. Even though persons ≥65 years of age is one of the higher coverage groups 

in the US, there still are about 25% to 30% percent of those folks who do not get vaccinated.

There could be some uninsured individuals.

Dr. Talbot added that the last part of the recommendation about getting whatever vaccine is 

available was something the WG was very concerned about. There was concern that if

someone went to a pharmacy that did not have one of the newer vaccines, that they would not 

get vaccinated at all. The idea was to allow them to get a standard dose vaccine if nothing else 

was available so that there would not be a missed vaccination opportunity. Perhaps the 

language could be worded more clearly to close the loop.

Dr. Lee stressed that one of the ways that disparities in children have been reduced is through 

the Vaccines For Children (VFC) program. To Dr. Goldman’s discussion points, frontline

providers already are doing a huge amount of counseling, preventive care, and healthcare for 

their patients. In addition, they are asked to bear the burden of the upfront cost of delivering 

vaccines. Vaccines are unlike any other intervention physicians provide. A Vaccines for Adults

(VFA) program could be incredibly impactful and powerful in reducing these disparities, 

particularly as there are increasing numbers of vaccines available for adults. Being able to help 

provider communities deliver these vaccines without financial risk to the providers would go a 

long way in making sure that the care that is needed is being provided in the moment that 

providers are caring for their patients. There are many providers who do not carry vaccines 

because it is a financial cost upfront that they are not sure is going to get fully reimbursed. This 

is an important service for the public good and is one that ACIP should emphasize and support 

going forward.
ACIP Meeting Summary June 22-23, 2022

22

Influenza WG: Summary/Proposed Recommendations for the 2022-2023 Influenza Season

Lisa Grohskopf, MD, MPH (CDC/NCIRD) next presented a brief summary of influenza vaccine 

safety and an overview of the proposed recommendations for the 2022-2023 influenza season.

For the 2021-2022 season, approximately 175 million doses of influenza vaccine were

administered in the US. No new safety concerns were identified in VAERS. Within the VSD, 

approximately 5.5 million doses of vaccine were administered. No new safety concerns were 

identified in this system either. Within the ISO’s Clinical Immunization Safety Assessment 

project (CISA), 2 ongoing studies have been enrolling this season. These are both coadministration studies and they are not currently enrolling since vaccination for the season has 

essentially ended or is close to ending. However, they will resume enrollment during the 2022-

2023 influenza season. The first is, “Safety of Simultaneous versus Sequential Administration of 

mRNA COVID-19 Vaccines and Quadrivalent Inactivated Influenza (IIV4) (Registered on 

ClinicalTrials.gov: NCT05028361). This study enrolled 73 participants ≥12 years of age during 

the 2021-2022 season. There was a safety panel assessment that noted no safety concerns.

The second is, “Safety of Simultaneous Vaccination with Zoster Vaccine Recombinant (RZV) 

and Quadrivalent Adjuvanted Inactivated Influenza Vaccine (aIIV4) (Registered on

ClinicalTrials.gov: NCT05007041). This study 102 participants ≥65 years of age during the 

2021-2022 season. There was a safety panel assessment of this study, which also identified no 

safety concerns.

To summarize the proposed recommendations for the 2022-2023 influenza season, the draft 

2022-2023 ACIP Influenza Statement contains many recommendations that are similar to

previous seasons. The core recommendation that annual vaccination is recommended for 

persons ≥6 months of age who do not have contraindications stands, with the hope that this is 

reaffirmed during the vote. There are 3 main updates. One is the US influenza composition for 

the 2022-2023 season. There is a section on the change in the approved age indication for

Flucelvax® Quadrivalent, which is the cell-culture-based inactivated vaccine(ccIIV4). This 

change in age indication occurred in the Fall after the publication of the last statement. The 

main topic of discussion during this session was the proposed new recommendation of 

language for influenza vaccinations of persons ≥65 years of age. 

This table lists the influenza compositions for 2022-2023 compared with the 2021-2022 

influenza season:
ACIP Meeting Summary June 22-23, 2022

23

For the 2022-2023 influenza season, all vaccines will be quadrivalent as there are no longer any 

trivalent vaccines. In addition, the influenza A(H3N2) and influenza B/Victoria components have 

been updated.

Until recently, Flucelvax® Quadrivalent was approved for persons ≥4 years of age. It was 

approved in March 2021 for persons ≥2 years of age and in October 2021 for persons ≥6 

months of age. With the last change, all standard-dose unadjuvanted IIV4s now approved for 

persons ≥6 months of age. 

In addition to these changes, the WG drafted the following proposed language for consideration 

for the new recommendation for influenza vaccine for persons ≥65 years of age:

“ACIP recommends that adults aged ≥65 years should receive one of the following 

higher dose or adjuvanted influenza vaccines, if available: quadrivalent high-dose 

inactivated influenza vaccine (HD-IIV4), quadrivalent recombinant influenza vaccine 

(RIV4), or quadrivalent adjuvanted inactivated influenza vaccine (aIIV4). No preference 

is expressed for any one of these three vaccines over the other two. If none of these 

three vaccines is available at an opportunity for vaccine administration, then any other 

age-appropriate influenza vaccine should be used.”

Discussion Summary

Dr. Schmader reported that the American Geriatric Society (AGS) endorses the preferential 

recommendation for high-dose adjuvanted influenza vaccine as presented. AGS sees this as a 

long overdue improvement in influenza vaccination policy for older adults. There is a population 

of older adults who do not receive vaccines at provider offices or retail pharmacies, the 

estimated 1.4 million residents of long-term care facilities (LTCF) who are vaccinated onsite.

This recommendation will provide clarity for that group as well.

Dr. Long suggested editing the first line of the recommendation to state “preferentially should 

receive,” removing “if available” at the beginning, and stating “there is no preference between 

these vaccines” at the end to ensure that people understand that it is no preference between the 

3 high-dose vaccines.

Dr. Poehling liked and agreed with Dr. Long’s suggestion. She suggesting stating that “there is 

no preference among these 3 vaccines.”

Dr. Hogue indicated that the American Pharmacists Association (APhA) has identified that the 

vast majority, if not all of the major national pharmacy chains, have connected their computers 

servers to the state immunization registries in those states where such connectivity has been 

allowed. Those pharmacy providers are, in fact, feeding data to the greatest extent that it is 

possible to send such data. There are approximately 20,000 independent pharmacies in the US. 

Those independent pharmacies have been making special efforts with their state health 

departments also to get connected. Funding for registries and getting systems established has 

been woefully lacking. There is a commitment on the part of the pharmacy community to make 

sure that immunization registries are complete and that the types of vaccines a patient has 

received are recorded accurately in the registry.
ACIP Meeting Summary June 22-23, 2022

24

Dr. Sanchez agreed with Drs. Long and Poehling on their proposed language edits. He 

emphasized that he wants a preference to be clear for the higher-dose or adjuvanted influenza 

vaccines over the standard dose instead of a wishy-washy-type of recommendation. He asked 

whether the language that “if they are not available, any other age-appropriate vaccine can be 

used,” could that be in the communications rather than in the vote.

Dr. Loehr pointed out that as a member of the WG, there was a strong feeling about not missing 

an opportunity to vaccinate and that was why the working “if available” was in there twice.

However, he was intrigued by Dr. Sanchez’s idea of taking out the last sentence and 

emphasizing the preferential aspect in the additional communication.

Dr. Fryhofer (AMA) said that speaking as a practicing physician, she strongly advised not taking 

out that last sentence. Physicians already have ordered their influenza supply for this year. If the 

last sentence is removed, she fears some patients may be denied any influenza vaccine 

whatsoever. Not having the sentence in the recommendation basically saying, “This way or the 

highway.”

Dr. Brooks concurred with Dr. Fryhofer for the same reasons, as well as the potential for missed 

opportunities. Reflecting on the equity slides showing lower rates of high-dose given to relevant 

minorities, the way the recommendation was stated seemed appropriate. Also, “prefer” seemed 

like weaker language than “should receive.” Perhaps the words “over the other two” could be 

removed. Otherwise, he agreed with the language as written.

Ms. Bahta supported changing the language to take out “if available” at the beginning. She 

emphasized that as Dr. Fryhofer mentioned, vaccine ordering already has occurred, which 

means that clinicians may not have any of the preferred vaccines. While she understood the 

desire to make this a strong statement, she pointed out that the available evidence is incredibly 

varied and evidence certainty was deemed low and very low in several aspects of the evidence.

Perhaps they were moving too fast to make this language very strong. From a clinical 

perspective, perhaps something specific needs to be included about not missing an opportunity.

Dr. Bell pointed out that given the body of evidence and all of the logistical concerns colleagues 

raised, it is important for ACIP to do everything they can to avoid misconceptions and confusion 

that somehow the high-dose vaccines are the only vaccines that they think people ≥65 years of 

age should be given.

Dr. Long disagreed with Dr. Bell. They saw that 80% of people ≥65 years of age already are 

getting a high-dose vaccine. This is not new information. Many studies have shown that as a 

high-dose is more effective in this age group and that the standard dose vaccines are not very 

effective. This will save an additional 2,000 lives and it will play out in a more equitable way for 

ACIP to that high-dose are better and should be used.

Dr. Schaffner indicated that the National Foundation of Infectious Diseases (NFID) was glad to 

join others in suggesting that the language should be “aged ≥65 years preferentially should 

receive one of the following higher dose or adjuvanted vaccines . . .” and that “if available” 

should be left in some form at the end of that statement. NFID strongly endorses a forceful initial 

statement.
ACIP Meeting Summary June 22-23, 2022

25

Dr. Lee agreed with others that there has been no other recommendation with this level of detail 

for an ACIP vote. Language such as “if none of these three vaccines is available” is typically in

the Clinical Considerations. The Clinical Considerations are where the importance of health 

equity, reducing disparities, pragmatic considerations, and the importance of not missing any 

opportunities for vaccine should be included and that the vote language should be focused on 

what the vote actually is. That said, she could live with it for this year since ACIP revisits this 

recommendation every year. She indicated that ACIP would adjourn for a break during which 

Dr. Grohskopf would edit the language based on the discussion, which ACIP could revisit after 

the break.

Regarding a question posed earlier about safety monitoring going forward, Dr. Grohskopf

indicated that she checked with the ISO about routine safety monitoring done on a vaccinespecific basis and learned that information is already being collected and summarized in 

VAERS in terms of the 3 vaccines of interest separately. Specific AEs of interest are routinely 

followed for these vaccines. Regarding the question about the percent of persons ≥65 years of 

age who are vaccinated in pharmacies, she was forwarded 1 report for persons ≥18 and older 

that indicated 39%. She will continue to seek additional information specifically on the proportion 

for persons ≥65 years of age. 

Vote #1: Influenza Vaccines for Persons ≥65 Years of Age 

Lisa Grohskopf, MD, MPH (CDC/NCIRD) presented the following revised proposed 

recommendation for influenza vaccine based on the discussion:

“ACIP recommends that adults aged ≥65 years preferentially receive one of the following 

higher dose or adjuvanted influenza vaccines: quadrivalent high-dose inactivated 

influenza vaccine (HD-IIV4), quadrivalent recombinant influenza vaccine (RIV4), or 

quadrivalent adjuvanted inactivated influenza vaccine (aIIV4). No preference is 

expressed for any one of these three vaccines. If none of these three vaccines is 

available at an opportunity for vaccine administration, then any other age-appropriate 

influenza vaccine should be used.”

Discussion Summary

Dr. Daley said he was in favor of the changes made but was either confused or concerned that 

the beginning says “preferentially” these vaccines are recommended, but then later says “no 

preference is expressed.” That could be interpreted as contradicting. Perhaps “No preference is 

expressed for any one of these three vaccines” could be removed.

Dr. Brooks agreed with what was stated and thought it seemed like a strong recommendation 

with “preferentially” at the beginning. He also favored keeping the last sentence for clarity rather 

than just moving it to the Clinical Considerations.

Dr. Grohskopf noted that the last sentence could remain for clarity but could be removed next 

year when the recommendation is revisited. The guidance is constructed such that there is not a 

separate Clinical Considerations document. 
ACIP Meeting Summary June 22-23, 2022

26

Motion/Vote #1: Influenza Vaccines for Persons ≥65 Years of Age

Dr. Talbot made a motion for ACIP to adopt the recommendation stating that, “ACIP 

recommends that adults aged ≥65 years preferentially receive one of the following higher dose 

or adjuvanted influenza vaccines: quadrivalent high-dose inactivated influenza vaccine (HDIIV4), quadrivalent recombinant influenza vaccine (RIV4), or quadrivalent adjuvanted inactivated 

influenza vaccine (aIIV4). If none of these three vaccines is available at an opportunity for 

vaccine administration, then any other age-appropriate influenza vaccine should be used.” Dr. 

Poehling seconded the motion. No COIs were declared. The motion carried with 15 affirmative 

votes, 0 negative votes, and 0 abstentions. The disposition of the vote was as follows:

15 Favored: Ault, Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long,

McNally, Poehling, Sanchez, Talbot 

 0 Opposed: N/A

 0 Abstained: N/A

 0 Absent: N/A

Vote #2: Proposed 2022-2023 Recommendations 

Lisa Grohskopf, MD, MPH (CDC/NCIRD) presented the following proposed affirmation for the 

2022-2023 Recommendations:

“Affirm the updated MMWR Recommendations and Reports, “Prevention and Control of 

Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on 

Immunization Practices, United States, 2022-2023 Influenza Season.”

Motion/Vote #2: Proposed 2022-2023 Recommendations

Dr. Sanchez made a motion for ACIP to adopt the recommendation to “Affirm the updated 

MMWR Recommendations and Reports, “Prevention and Control of Seasonal Influenza with 

Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United 

States, 2022-2023 Influenza Season.” Dr. Long seconded the motion. No COIs were declared.

The motion carried with 15 affirmative votes, 0 negative votes, and 0 abstentions. The 

disposition of the vote was as follows:

15 Favored: Ault, Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long,

McNally, Poehling, Sanchez, Talbot 

 0 Opposed: N/A

 0 Abstained: N/A

 0 Absent: N/A
ACIP Meeting Summary June 22-23, 2022

27

Discussion Summary 

Subsequent to the vote, Dr. Lee invited ACIP members to make a statement about the rationale 

for their vote and/or to share any additional general comments:

Dr. Talbot said she was super excited that vaccinations are being improved for older adults and 

to hear so many seniors and senior groups advocating for vaccines. The prevention of 

hospitalizations, reducing the time on disability, and improving life is incredibly important for US

seniors who are a growing population. While these influenza vaccines are better, they are not 

yet the “homerun” that is needed. She encouraged current vaccine manufacturers to continue to 

seek the “Holy Grail” of an influenza vaccine that will work every time and will work for older and

immunosuppressed patients. She thanked ACIP members for their votes and for looking out for 

the nation’s seniors and encouraged the groups who are advocating for older adults to please 

continue this work. 

Dr. Kotton emphasized how wonderful it is to have this influenza vaccine recommendation for 

older adults. She highlighted that the immunocompromised patient population still remains

very vulnerable to influenza, and although the data for that population are not as robust,

hopefully in the near future, ACIP also can make a recommendation for that population to

receive these likely improved and better vaccines to provide them with better protection. As it 

stands, these vaccines are typically not covered by insurance because they are not 

recommended. Therefore, some of her patients have to pay out-of-pocket. Not only is this 

expensive, but also it is off-label use. Hopefully, the immunocompromised patient population will 

be the next frontier.

PNEUMOCOCCAL VACCINES 

Session Introduction

Katherine A. Poehling, MD, MPH (ACIP, WG Chair) provide an introduction and overview of

the pneumococcal vaccine session on behalf of the Pneumococcal Vaccine WG. This table 

shows the current 13-valent pneumococcal conjugate (PCV13) and 23-valent pneumococcal 

polysaccharide (PPSV23) vaccines. The new 15-valent pneumococcal conjugate vaccine 

(PCV15) includes PCV13 serotypes + 22F and 33F:

The current pneumococcal vaccine recommendations for children are as follows:





PCV13 Routine Recommendation

− 4-dose PCV13 series at 2, 4, 6, and 12–15 months (3+1 schedule)

PCV13 Catch-Up Options

− Healthy children through age 59 months

− Children with underlying medical conditions through age 71 months
ACIP Meeting Summary June 22-23, 2022

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

−

−



−

−





PCV13 and PPSV23 for Children 24–71 Months of Age with Underlying Medical Conditions

Complete recommended PCV13 doses followed by PPSV23 ≥8 weeks later

Children who are immunocompromised or with sickle cell disease or asplenia  2nd

dose of PPSV23 recommended 5 years after the 1st dose

PCV13 and/or PPSV23 for Children 6–18 Years Old with Underlying Medical Conditions

One dose of PPSV23 for children with chronic heart/lung disease, or diabetes

One dose of PCV13 (if never received) followed by PPSV23 ≥8 weeks for children with 

immunocompromising conditions, cerebrospinal fluid (CSF) leak, or cochlear implant

• For children with immunocompromising condition, give a 2nd dose of PPSV23 ≥5 

years after the first PPSV23 dose

The general principles addressed during this session were to consider use of PCV15 as an 

option to PCV13 according to the currently recommended PCV13 dosing and schedules and 

consider interchangeable use of PCV15 and PCV13. No changes were to be made for the 

PPSV23 recommendations. The 2 policy questions being considered by the WG include:

Should PCV15 be routinely recommended for US children <2 years of age as an option for 

pneumococcal conjugate vaccination according to currently recommended dosing and 

schedules?

Should PCV15 be recommended for US children 2–18 years of age with underlying medical 

conditions as an option for pneumococcal conjugate vaccination according to currently 

recommended dosing and schedules?

To provide a timeline of what is coming in the future, it is anticipated that a PCV-20 vaccine 

would be licensed in 2023 and PCV15 was just licensed. In February 2022, the WG presented

the pediatric pneumococcal disease epidemiology, the Phase 2/3 PCV15 studies in children

and the first part of the EtR Framework and GRADE. The WG received a lot of questions about 

fever and the potential for febrile seizures and spent a lot of time paying attention to that. The 

agenda for this session included presentations on PCV15 use in children, a cost-effectiveness 

analysis, an EtR Framework updates, and a vote if acceptable. During the October 2022 ACIP 

meeting, the WG will address questions related to PCV15 and PCV-20 use in adults.

PCV15 Pediatric Clinical Development Program Update

Natalie Banniettis, MD, FAAP (Merck) reminded everyone that that she presented an

overview of the Phase 3 results of the V114 pediatric clinical development program to ACIP on

February 24, 2022. She thanked the ACIP for their post-review of the V114 pediatric clinical

data and for the opportunity to present again during this meeting. The first portion of this 

presentation focused on safety in the Phase 3 pediatric program, including a summary of the 

pediatric database and an analysis of temperatures ≥104°F. The second portion of the 

presentation included a brief review of key results of the subgroup analysis requested by the US 

FDA. 

Starting with the Phase 3 safety data, the V114 pediatric clinic program was designed to target 

pediatric populations in which PCV vaccination is indicated and to generate a robust safety and 

immunogenicity profile for V114 in children. V114 is approved by the US FDA for immunization
ACIP Meeting Summary June 22-23, 2022

29

of individuals ≥6 weeks of age for the prevention of invasive disease caused by the 15

pneumococcal serotypes included in the vaccine. The US filing for licensure of V114 in children 

is supported by 7 clinical trials among children 6 weeks through 17 years of age. In these trials, 

there were approximately 7,200 participants of whom about 4,800 received V114. Of these,

approximately 6,100 were healthy infants 6 through 12 weeks of age of whom approximately

4,300 received V114. Safety data from 3 Phase 2 studies comprised of a total of approximately 

4,500 healthy infants, including approximately 3,000 recipients of V114 who were integrated for 

analysis based on similarities and study design and dosing schedule. This population is referred 

to as the integrated safety summary in infants (ISS) in this presentation and is considered to be 

the most robust dataset upon which to assess the safety of V114 in healthy infants who 

received a 4-dose regimen in alignment with the ACIP recommended schedule.

Previously presented to the ACIP, the ISS population included approximately 3,000 infants in 

the V114 group and approximately 1,500 in the PCV13 group. The proportions of participants 

with AEs (e.g., injection site systemic AEs, vaccine-related AEs, and SAEs) were generally

comparable between the groups. Notably, there were no discontinuations of the study 

intervention due to AEs. In both groups, the majority of AEs were mild or moderate in intensity 

with a duration of 3 days or less. The conclusion of the ISS analysis was that the V114 safety 

profile is generally comparable to that of PCV13.

In terms of how temperatures are collected and evaluated in the pediatric program, parents are 

given a digital thermometer and an electronic vaccination report card (eVRC) upon enrollment

into the study. Parents are prompted by the eVRC to enter daily maximum body temperatures

at approximately the same time each day from Day 1 through Day 7 post-each vaccination and 

Days 8 through 14 if febrile. The rectal method of temperature measurement was preferred per 

protocol. On day 15, the investigator reviewed temperature data with the parent and entered 

new AEs into the database. For example, an unsolicited AE of pyrexia could have been entered 

or a diagnosis such as upper respiratory tract infection would have been entered if addition 

signs or symptoms were present. Contemporaneously, the sponsor’s clinical team reviewed

temperature data and AEs to ensure complete and accurate reporting to the fullest extent 

possible.

As previously presented, the distribution of solicited daily temperatures in the 7 days postvaccination was generally comparable between the intervention groups in the ISS analysis with 

the majority being afebrile in the 7 days post-vaccination. Of those with temperatures ≥100.4°F, 

the majority were <101.3°F in both groups and the proportion of participants reporting

temperatures ≥104.0°F was low in both groups after each vaccination. Turning attention to the 

daily temperatures following the toddler dose as broached on February 24, 2022 by the ACIP 

members, at the post-toddler dose timepoint, the sample size included was approximately 2,800

participants in the V114 group, which was more than double the sample size included in the

PCV13 group due to the randomization schemes utilized in this study. A subset of 19 

participants reported body temperatures of ≥104.0°F with a point estimate of 0.7% and 3 

participants in the PCV13 group reported temperatures of ≥104.0°F with a point estimate of 

0.2%.

Merck was asked to share additional information about this subset by the ACIP, as members 

noted a numerical imbalance between the groups. Therefore, an analysis was performed of the 

aforementioned subset using several statistical methods including weighted and unweighted 

approaches. Of note, Protocol 31, the large safety study, contributed the majority of participants 

in the integrated analysis with approximately 2,400 participants randomized 5:1 to receive V114

or PCV13, respectively. Given that the randomization ratio in Protocol 31 differs from that of the 
ACIP Meeting Summary June 22-23, 2022

30

other studies included in the integrated analysis using 1:1 randomization, a weighted approach

to pooling the data across studies reduced potential bias in the estimate of the risk differences.

Regardless of the statistical method used, the difference between the vaccination groups was 

small and not statistically significant.

Continuing now with the same subset of participants with maximum body temperatures 

≥104.0°F following Dose 4 but focusing only on the 19 recipients of V114, in regard to AEs

following the toddler dose, no febrile convulsions or vaccine-related SAEs were reported in 

these 19 participants. Of the 19 participants, 13 had AEs of pyrexia reported by the investigator 

with the majority of these pyrexia events resolving within 3 days and all but 1 were non-serious 

AEs. The single SAE of pyrexia was deemed non-vaccine-related by the study investigator and 

occurred in a participant who presented with respiratory and gastrointestinal symptoms. Among 

the 19 participants, 10 reported concurrent AEs that were suggestive of an underlying infectious 

process along with the reported temperatures of ≥104.0°F. Of the 19 participants, 15 reported 

these temperatures during the influenza season. Additionally, 9 of the 19 had onset after Day 4

post-vaccination and as such, were less likely to be related to PCV vaccination.

To summarize, in participants with maximum body temperatures ≥104.0°F after the toddler dose

in the integrated analysis, the between group differences in incidence were small and not

specifically significant based on both weighted and unweighted analyses. No vaccine-related 

SAEs of febrile convulsion were reported among the V114 recipients. Maximum body

temperatures may have been confounded by underlying infection and concomitant vaccination.

As for all Merck vaccines, post-marketing safety surveillance of V114 via routine

pharmacovigilance activities will be conducted to ensure the safety profile remains adequately 

characterized.

Transitioning to the second portion of the presentation, Dr. Banniettis briefly highlighted key 

results of the subgroup analyses performed at the request of the FDA. As background, 2 

different pentavalent combination vaccines were used in Protocol 27, the interchangeability 

study, and Protocol 29, the pivotal study. PentacelTM was used at study sites located in the US 

and Puerto Rico, and PentavacTM was used at study sites located in Turkey and Thailand. Each 

of these vaccines is manufactured and marketed by Sanofi Pasteur and contains diphtheria, 

tetanus, acellular pertussis, inactivated polio, and polysaccharide conjugate antigen.

PentavacTM contains 2 components of pertussis antigen and PentacelTM contains 5 

components. In each study, approximately 70% of participants in each vaccination group

received PentacelTM.

In March 2022, the FDA requested additional analyses for Protocol 29 and Protocol 27 based 

on a subgroup of study participants who received PentacelTM concomitantly with PCV, excluding 

those who received PentavacTM. The conclusions of the subgroup evaluation limited to 

PentacelTM recipients were largely unchanged from the original analysis despite the reduced 

sample size by approximately 30% in both groups in both studies. The ad hoc subgroup 

analyses are descriptive in nature and no formal statistical testing was performed, given that the 

studies were not powered for success with a smaller sample size. Nonetheless, all of the 

original criteria were met except for mumps. The 30% reduction in sample size led to a 

decrease in power for the MMR non-inferiority evaluation in the PentacelTM subgroup. However, 

response rates to mumps were high in the V114 group and comparable to PCV13. To

summarize, the immunogenicity and safety of V114 relative to PCV13 and the ad hoc subgroup 

analysis limited to participants who received PentacelTM as a concomitant vaccine were 

consistent with the primary analysis in the overall population.
ACIP Meeting Summary June 22-23, 2022

31

In terms of key conclusions of the V114 pediatric clinical program, in children with an unmet 

medical need for pneumococcal disease prevention, V114 is well-tolerated, with a safety profile

that is consistent with licensed PCVs. V114 induces robust immune responses to the 13 shared 

serotypes with PCV13. V114 is superior to PCV13 for the shared serotype 3 and the unique

serotypes 22F and 33L, which are of high public health importance. V114 can be administered 

concomitantly with routine childhood vaccines. Therefore, V114 has the potential to significantly 

address the burden of remaining pneumococcal disease due to vaccine types and leading nonvaccine types in children. 

Discussion Summary 

Dr. Kimberlin (AAP Redbook) asked when PCV15 was approved by the FDA for use in children.

Dr. Fink (FDA) indicated that FDA approved the efficacy supplement for use of PCV15 in 

children 6 months through 17 years of age on Friday, June 17, 2022. 

Ms. Bahta asked whether influenza was confirmed for any of the 15 of the 19 children who had 

high fevers during that influenza season and/or whether other infections were confirmed.

Dr. Banniettis indicated that no cases of influenza were confirmed in any of those cases, but 

other infections were. These included RSV and other respiratory viruses and gastrointestinal 

viruses.

Referring to Slide 5, Dr. Daley noted that there were 2 listed SAEs in the PCV15 group for which 

he requested additional information.

Dr. Banniettis indicated that both were SAEs of pyrexia, one of which occurred on the same day 

as Dose 1. The maximum body temperature was 100.4°F. This participant was located in the 

US. The concomitant vaccines were received included RotaTeqTM, Pentaxim®, and HiberixTM. 

The reasons for the admission for this particular child was due to significantly elevated

hyperbilirubinemia in the context of a fever of 100.4°F. There was a concern for gram-negative 

sepsis, which was ruled out. The second case occurred on the same day as Dose 3. The

maximum body temperature in that participant was 102.9°F. This participant was located in 

Thailand. Concomitant vaccines included DTaP, Hib, Hep B, and oral polio vaccine (OPV). This 

particular participant was admitted specifically because there was impressive tachycardia and

suspicion of bacterial sepsis, which was ruled out. 

Economic Analysis and Public Health Impact of PCV15 Use in Children

Dr. Andrew J. Leidner (CDC/NCIRD) presented the results of the economic analysis and 

public health impact of PCV15 use among children in the US. The contents of this presentation 

were developed by 2 different modeling teams, the CDC model team and the Merck model 

team. This presentation summarized the key findings from these 2 models. Previous studies 

have found that pneumococcal vaccination averts thousands of deaths and saves millions of 

dollars in direct medical costs.3 In particular, previous studies found PCV13 was cost saving 

when compared to PCV7.4 This presentation focused on 2 newer models that examined the 

cost and benefits of including PCV15 as an option in the childhood immunization schedule, the

CDC and Merck models. Both models completed the CDC economic review following the 

procedures in the ACIP Guidance for Health Economic Studies.5

3

 Zhou et al. 2014 

4

 Messonnier et al. 2009; Rubin et al. 2010 

5

 Leidner et al. 2019
ACIP Meeting Summary June 22-23, 2022

32

The broad research question motivating the CDC and Merck model studies was, “What is the

cost-effectiveness and public health impact of including PCV15 as an option in the immunization 

schedule for children?” This broader question can be broken down into 2 sub-questions about 

cost-effectiveness and the prevented disease burden of using PCV15 as compared to PCV13.

Notably, both models directly compared the use of PCV15 to the use of PCV13. In a direct

comparison like these models have done, a practical implication is that the vaccinated

individuals in a particular strategy in the model all will receive one type of vaccine. That is, all 

children in a PCV13 strategy received PVC-13 and all children in a PCV15 strategy received 

PCV15. Then the cost and benefits from these 2 strategies were compared directly. This issue

will come up again later in terms of some of the limitations of the prevented disease burden

results.

Starting with the first research question about the cost-effectiveness of PCV15, there were 2 key 

assumptions that went into both models. The first key assumption was VE. Both models 

assumed that PCV15 and PCV13 have the same VE for PCV13-type disease. They also both

assumed that PCV15 offered additional disease protection for the 2 serotypes that included in 

PCV15 but not included in PCV13. These 2 assumptions taken together mean that in both

models, the use of PCV15 prevents more episodes of pneumococcal disease than the use of 

PCV13. The second key assumption for the cost-effectiveness analysis was the cost of a dose 

of vaccine. In their base case, both models assumed that the average cost of PCV15 was less 

than the average cost of PCV13. There was a slight difference in these cost inputs across the 2

models. The CDC model base case assumed 1 dose of PCV15 was about $3 less than 1 dose 

of PCV13 on average. The Merck model base case assumed on average that 1 dose of PCV15

was about $1 less than a dose of PCV13.

Keeping in mind the 2 key assumptions, it should be no surprise that the base case results of 

both models were that PCV15 use was found to be cost-saving when compared to PCV13 use. 

This result was consistent across a number of sensitivity analyses and scenarios in which the 

cost of a dose of PCV15 was increased. To be clear, the term “cost-saving” in economic

analyses like these means that the total costs are reduced and that the health outcomes are 

improved when the use of PCV15 was compared to the use of PCV13. Again, a cost-saving 

result was not surprising given that it was assumed PCV15 prevents more disease while costing 

about the same as PCV13. Another way to state that health outcomes are improved is to say

that disease burden is prevented.

Focusing on approximately how much additional disease burden might be prevented by the use 

of PCV 15, Dr. Leidner addressed the question of preventive disease burden by first discussing 

a few more assumptions in the 2 models. A few key model characteristics include model type, 

model duration in years, and incidence rates. The CDC model followed a single cohort who 

were 0 years old (newborns) at the start of the model and followed them for 17 years. In 

contrast, the Merck model used a multi-cohort approach, meaning that at the start of the model, 

there was not a single cohort of newborns. Instead, there were 100 cohorts—1 cohort for each 

year of ages 0 to 100 years. The 100 Merck model cohorts were followed for 100 years, with a 

new cohort being born and added to the population at each year in the model. Considering 

these differences, the overall population size of the Merck model was considerably larger than 

the population represented in the CDC model. This model characteristic will go a long way 

toward explaining the differences between the base case results of the 2 models. While the 

Merck model had a much larger population in the base case, the Merck model also ran several

scenarios using a single cohort very similar to the CDC model base case. These single cohort 

scenarios were the main results used in the discussion on preventive disease burden. While the 
ACIP Meeting Summary June 22-23, 2022

33

Merck model single cohort results and the CDC base case results were fairly comparable, they 

were not identical. Some of the remaining differences in the 2 models’ estimates of preventive 

disease burden can be attributable to differences in incidence rate assumptions which for the 

CDC model included higher incidence rates for inpatient non-bactearemic pneumonia (NBP) 

and for the Merck model included higher incidence rates for invasive pneumococcal disease 

(IPD), outpatient NBP, and acute otitis media (AOM).

Now looking at the main results from the 2 models’ estimates of preventive disease burden 

using PCV15 as compared to PCV13. The Merck base case represented a substantially larger 

population over much longer model duration, so those estimates are larger than the results in

that used single cohorts. Much of the differences in IPD, NBP, AOM, and deaths can be

explained by differences in inputs of incidence. The differences in quality-adjusted life year

(QALYs) gained are due to both incidence inputs and health utility inputs. The estimates from 

the single cohort scenarios were used to construct the range for each of the prevented disease 

outcomes. If one cohort of infants received PCV15 instead of PCV13, the range of disease

burden prevented might be expected to look like the values in this table:

There are a few considerations to keep in mind. This table is for 1 cohort that receives PCV15 

instead of PCV13. If multiple cohorts were given PCV15 instead of PCV13, the prevented

disease burden would be greater. If adoption of PCV15 is lower, meaning that there is a mixture 

of use between PCV15 and PCV13, the prevented disease burden would be smaller. This point 

was alluded to early in the presentation when these models were described as using 1 vaccine 

or another for a given strategy in their direct comparisons. Finally, if indirect effects to older

adults were included in these static cohort scenarios, the prevented disease burden would be 

greater. A caveat to that would be that if vaccination coverage rates among US adults for 

PCV15 and PCV20 were high, then any indirect effects from childhood use of PCV15 could be 

modest.

The first major conclusion from the 2 models was that PCV15 use appears to be cost-saving

when compared to PCV13. PCV vaccines going back to PCV7 have been found generally to 

reduce direct medical costs and improve health outcomes. Two models in previous research 

have shown that PCV13 use was cost-saving when compared to PCV7. The 2 models 

presented during this session concluded that PCV15 use is cost-saving when compared to

PCV13. In these 2 models and the key assumptions that led to this result were VE and vaccine 

cost. For VE, the WG discussed the uncertainty of the VE assumptions in light of these 

assumptions being based upon immunogenicity data. The other assumption was vaccine cost. 

Another interesting point about vaccine cost in these assessments is that PCV15 was less 

expensive or approximately the same as PCV13. In the older studies that compared PCV13 to 

PCV7, PCV13 was actually more expensive than PCV7 and was still found to be cost-saving

when compared to the less expensive alternative. The second major conclusion was that

pneumococcal vaccination of children has historically had a notable health impact. That also 

may be true for the use of PCV15 since both models estimated that overall health is improved 
ACIP Meeting Summary June 22-23, 2022

34

when PCV15 is used as compared to PCV13. This finding is certainly conditional on the

assumption in both models that VE for PCV15 was equal to PCV13 for PCV13-type disease and

was assumed to provide additional protection for the 2 additional serotypes. Differences in the

estimated prevented disease burden appear to be due to differences in model structure and 

input values. With all these differences in consideration, the CDC model could be considered

more conservative than the Merck model.

Discussion Summary 

Dr. Loehr asked whether in the Merck 100-year cohort study consideration was given to the 

possibility that PCV15 would last beyond childhood to provide additional benefit to adults 

because there would be less disease in the environment.

Dr. Leidner acknowledged that this could be possible. Both models assumed that direct 

protection from the vaccine would wane to 0 after approximately 15 years. Both models also 

assumed that there is an amount of indirect protection or indirect effects, but it is quite 

complicated. In the Merck base case, indirect effects were allowed to protect individuals in Year 

1 of the model who were ≥65 years of age. Indirect effects also were allowed to provide 

protection to the younger cohorts for whom direct protection had waned to 0 after the 15-year 

period. That said, the Merck model only assumed that indirect effects would occur with respect 

to IPD and not NBP or otitis media. To summarize the CDC model assumptions, in their single 

cohort base case, indirect effects did occur and did provide benefit to individuals who were nonvaccinated in that cohort and for individuals whose direct protection had waned to 0 over the 17-

year duration of the model. What the CDC model did not include was protection from 

vaccinating newborns that would then immediately transfer to persons ≥65 years of age in Year 

1 of the model. The caveat to assuming indirect effects would apply in Year 1 to persons ≥65 

years of age is that those individuals are already recommended to receive PCV15 and PCV20. 

If they are getting direct protection from the vaccines that they are recommended to receive,

the indirect effects may be more modest.

Dr. Sanchez asked whether the assumption that the average cost for PCV15 is less than that of 

PCV13 was a known fact. He was surprised that any new vaccine would be cheaper than an 

older one.

Dr. Kobayashi said that PCV15 is already licensed for use in adults. There is a private market 

price available on the CDC website for PCV15. When compared to the price of PCV13, PCV15 

is actually priced lower. CDC also communicated with Merck about what the appropriate 

estimate for the vaccine cost would be. Sensitivity analyses were performed for both models, 

which provided some range to the estimated cost. 

Updates to the EtR: Use of 15-valent Pneumococcal Conjugate Vaccine in Children

Miwako Kobayashi, MD, MPH (CDC/NCIRD) presented the summary of the Pneumococcal 

WG’s interpretation of the EtR Framework for use of 15-valent pneumococcal conjugate 

vaccination in children. During the February 2022 ACIP meeting, the WG presented its 

interpretation of the EtR Framework domains of the public health problem, benefits and harms, 

values, and equity. After review of additional data and discussion following the February 2022 

ACIP meeting, the WG updated the interpretation on EtR domains for benefits and harms and 

equity. During this session, Dr. Kobayashi provided a summary of the WG’s interpretation of 

each EtR domain including the domains of acceptability, feasibility, and resource use that were 
ACIP Meeting Summary June 22-23, 2022

35

not presented previously, as well as the rationale for the WG’s updated interpretation for the 

domains of benefits and harms and equity. As a reminder, the 2 PICO questions are:

 Should PCV15 be recommended as an option for pneumococcal conjugate vaccination 

according to currently recommended dosing and schedules for US children <2 years of age? 

 Should PCV15 be recommended as an option for pneumococcal conjugate vaccination 

according to currently recommended dosing and schedules for US children 2–18 years of 

age with underlying medical conditions?

Both policy questions compare PCV15 to PCV13 use. The outcomes considered to be critical 

include vaccine type-IPD (VT-IPD), VT-pneumococcal pneumonia (VT-pneumonia), VT-AOM, 

VT-pneumococcal deaths, and SAEs following immunization.

The first domain is public health problems. In this presentation, IPD refers to an illness with 

pneumococcal detection in a normally sterile site such as blood or in cerebrospinal fluid (CSF). 

Examples include pneumococcal meningitis, bacteremia, or bacteremic pneumonia. Examples 

of non-invasive disease include NBP or AOM, which has higher disease burden. In children, 

AOM is one of the most common reasons for outpatient care and antibiotic prescribing.6 In 

2018, the incidence of AOM due to any cause in children <2 years of age was approximately 

75,000/100,000 person years.7 Pneumococcus is estimated to account for 24% of clinically 

diagnosed AOM in children.8 In 2014, the estimated incidence of all caused pneumonia in 

children was approximately 1,300 to 4,000/100,000 person years in children ≤17 years of age.9

Studies using administrative data have shown decline in incidence of AOM and hospitalization 

due to all-cause and pneumococcal pneumonia in children post-PCV introduction.10

Looking at the incidence rates of IPD among children <5 years of age during 2007-2019 in 

CDC’s Active Bacterial Core Surveillance (ABCs) data, rates of PCV13-type IPD declined 

sharply after introduction of PCV13 for children in 2010. After 2013, declines in PCV13-type IPD 

rates plateaued at less than 2 cases/100,000. This trend continued through 2019. Rates of nonPCV13 serotypes remained relatively stable over this time period. In terms of IPD incidence by 

age in 201911 show that in children, pneumococcal disease burden decreases with increasing 

age. In children 5-17 years of age, around 25% of the cases had a medical condition that is an 

indication for PCV13.

In terms of children aged 6-36 months living in Rochester, New York,12 children who developed 

AOM had nasopharyngeal (NP) swabs or middle ear fluid (MEF) collected. Among children with 

AOM with pneumococcal detection, the 2 additional serotypes included in PCV15 but not in 

PCV13 were identified in 6% to 8% of children. The proportion of IPD caused by the serotypes 

included in PCV13 was 21% to 34%. The proportion due to the 2 additional serotypes included 

in PCV15 but not in PCV13 was 16% to 17%.

The WG determined that pneumococcal disease is of public health importance in children. This 

interpretation is unchanged from February 2022.

6 Tong BMC Health Services Research 2018; Lewnard CID 2021; Hersh et al. Pediatric 2011,

7 Hu et al. BMCID

8 Kaur et al. EJCMID 2022

9 Tong BMC Health Services Research 2018

10 Hu et al. BMCID; Simmonsent, Lancet Resp Med 2014 11 Active Bacterial Core Surveillance (ABCs) Report Emerging Infections Program Network Streptococcus pneumoniae, 2019. 

Available: SPN_Surveillance_Report_2019.pdf (cdc.gov) 

12 Adapted from Kaur et al. EJCMID 202
ACIP Meeting Summary June 22-23, 2022

36

Regarding the domain of benefits and harms, the WG determined that the desirable anticipated 

effects from PCV15 use were moderate for both PICO questions. This was unchanged from the 

February 2022 ACIP meeting. Dr. Kobayashi summarized the evidence that the WG reviewed 

during the February meeting. For evidence on routine PCV15 use in children <2 years of age, 

the WG identified 5 RCTs. All 5 studies were compared to those who received PCV13. The first 

4 studies highlighted in the following table provided data on both immunogenicity and safety. 

This include V114-027, which evaluated the product interchangeability with PCV13 and PCV15 

and V114-024, which evaluated catch-up schedules at different ages using PCV15: 

The fifth study, V114-031, was an RCT focusing on safety and tolerability in healthy infants 

stratified between full term and preterm infants. Infants were given either PCV15 or PCV13 

using the 3+1 schedule, which is the PCV schedule currently used in the US. This study was 

added to the 4 studies above for the assessment of evidence on safety. 

To summarize the evidence for the studies considered for the benefits of routine PCV15 use in 

children <2 years of age, immunogenicity from PCV15 use was non-inferior to PCV13 for all 13 

serotypes post-Dose 4. Post-Dose 3, immunogenicity from PCV15 was non-inferior to PCV13 

for 12 of 13 shared serotypes, with serotype 6A missing the non-inferiority criteria. PCV15 had 

statistically significantly higher immunogenicity for serotype 3 and for the 2 serotypes unique to 

PCV15, which are 22F and 33F. The certainty assessment for indirectness was downgraded to 

serious since the 4 studies were all immunogenicity studies and correlates of protection have 

not been established for some of the critical outcomes considered. The overall certainty of 

evidence was 2 (moderate).

For evidence on PCV15 use in children with underlying medical conditions, the WG identified 2 

RCTs by Merck. The first study, V114-023, evaluated 1 dose of PCV15 in children with sickle 

cell disease. The second, V114-030, evaluated PCV15 in series with PPSV-23 in children living 

with HIV. Both compared PCV15 use with PCV13 use. To summarize the evidence from these 2 

studies, non-inferiority assessments were not performed in these studies, so the findings were 

descriptive. Post-PCV dose, PCV15 had higher immunogenicity compared with PCV13 for 6 to 

7 of 13 serotypes and the 2 unique serotypes, 22F and 33F. In one study that assessed PCV15 

or PCV15 use followed by PPSV-23, the immunogenicity after PPSV-23 in the group that 

received PCV15 was numerically higher compared with those who received PCV13 for 3 of 13 

serotypes but not for unique serotypes 22F and 33F. For the assessment of certainty of 
ACIP Meeting Summary June 22-23, 2022

37

evidence, indirectness was downgraded to serious since the studies were immunogenicity 

studies and correlates of protection have not been established for some critical outcomes. 

Imprecision was downgraded due to small sample size. Therefore, the overall certainty of 

evidence was 3 (low).

For the second question regarding how substantial the undesirable anticipated effects are, the 

WG interpretation for the undesirable anticipated effects from routine PCV15 use in children 

aged <2 years of age was changed from minimal to small after further WG discussions. Upon 

closer review of safety data, some WG members were concerned about the potential for higher 

reactogenicity in children who received PCV15 compared with children who received PCV13. 

The safety data were based on descriptive analysis, and the WG believes that uncertainties 

remain. Infrequency of rare AEs, such as serious vaccine-related AEs or fever of ≥104.0°F postDose 4, certainty was reflected in the updated GRADE table for assessment on safety of routine 

PCV15 use compared with PCV13 use in children <2 years of age.

To summarize the findings from 5 RCTs, 5 vaccine-related SAEs were reported in children who 

received PCV15 across 5 studies. The WG downgraded the certainty assessment for 

imprecision twice, first due to the small number of events of the outcome in both arms and 

second due to a wide 95% confidence interval of the relative risk of events that could not 

exclude the potential for increased harm or benefit. As a result, the overall certainty of evidence 

on safety was changed from 2 (moderate) to 3 (low). The undesirable anticipated effects of 

using PCV15 in children with underlying medical conditions was determined to be minimal, 

which remained unchanged. In the 2 studies that assessed PCV15 use among children with 

underlying medical conditions, no vaccine-related SAEs were reported. The certainty 

assessment of imprecision was downgraded twice to very serious, once due to no report of the 

outcome of interest and again for very small sample sizes. Therefore, the overall certainty of 

evidence is 3 (low). The WG interpretation on the balance between desirable effects relative to 

the undesirable effects were changed from favors the intervention to favors both for both PICO 

questions. The changes were made after it was clarified that the comparison that is made is to 

PCV13 use in children, not the balance between undesirable and desirable effects of PCV15 

use. While PCV15 is expected to prevent more disease against 2 additional serotypes 

compared with PCV13, the WG believes that there is uncertainty of the added impact of PCV15 

use compared with PCV13 use given that there are currently no clinical efficacy data. 

Additionally, there are some uncertainties about the potentially higher reactogenicity from 

PCV15 use compared with children who received PCV13.

The next domain is values and preferences. Studies on values and preferences of PCV15 use

in children were not identified. However, vaccination coverage for 3 or more doses of PCV13 by 

24 months of age has been high, demonstrating that the target population probably feels that 

the desirable effects of PCV vaccination outweigh the undesirable effects. For the first question 

regarding whether the target population feels that the desirable effects from vaccination are 

large relative to undesirable effects, the WG interpretation was split between “probably yes” and 

“yes” mainly due to the uncertainties about the magnitude of added benefit of PCV15 use 

compared with PCV13 use. For the second question regarding whether there is important 

uncertainty about or variability in how much people value the main outcomes, the WG 

determined that there is probably non-important uncertainty or variability.
ACIP Meeting Summary June 22-23, 2022

38

The next domain is acceptability. For this domain, the WG reviewed Merck’s provider 

preferences survey related to multivalent pneumococcal conjugate vaccines that was 

administered in November 2021. Responders included a sample of 600 healthcare providers 

(HCPs) who prescribe or administer 10 or more pneumococcal vaccines per month. The HPCs 

consisted of 530 physicians and 70 physician assistants (PAs) or nurse practitioners (NPs). The 

key findings from the survey were that about 40% of HCP believe that the risk of developing 

pneumococcal disease is higher than the risk of developing other vaccine-preventable diseases

such as measles, mumps, rubella, rotavirus, chickenpox, diphtheria, tetanus, or pertussis in 

children aged under 24 months of age. HCPs believe that pneumococcal vaccines are highly 

important for children under 24 months of age. HCP stated that the following clinical features 

were important in pneumococcal vaccine choice in children under 24 months of age: IPD 

indication (63%), safety and side effects (47%), greater immune response to certain diseasecausing serotypes (46%), and overall immune response across vaccine serotypes (45%).

Therefore, the workgroup believes that recommending PCV15 as an option for pneumococcal 

conjugate vaccination according to currently recommended dosing and schedules for children is 

“probably acceptable” to key stakeholders.

Next is resource use. As Dr. Leidner presented, assuming that PCV15 has similar effectiveness 

as PCV13 against PCV13-type disease, PCV15 protects against 2 additional serotypes in 

assuming that PCV15 is less expensive than PCV13. Both the CDC and Merck models show 

that use of PCV15 in the childhood immunization schedule reduces direct medical cost and 

improves health compared with using PCV13. Regardless, the WG interpretation on routine 

PCV15 use in children aged under 2 years of was split between “probably yes” and “yes.” This 

was due to uncertainties about the clinical efficacy of PCV15, as well as the actual vaccine 

price. Some WG members considered the possibility of low but increased healthcare utilization 

in the PCV15 recipients due to increased reactogenicity. For similar reasons, the WG 

interpretation on resource use was “probably yes” for PCV15 use in children 2–18 years of age 

with underlying medical conditions.

The WG’s interpretation for the equity domain was updated. Certain groups have lower 

pneumococcal conjugate vaccine coverage than others. According to the 2020 National 

Immunization Survey (NIS) data, PCV coverage of 4 or more doses by 24 months of age was 

lower among children who are uninsured, Black, non-Hispanic, living in a non-metropolitan 

statistical (MSA) area, or living in the lowest federal poverty level. There are certain populations 

who have higher pneumococcal disease burden than others. For example, IPD rates among 

Native American children <5 years of age remained approximately 4-fold higher than in children 

of all races in 2018.13 Alaskan Native infants had a 1.6-fold higher rate of AOM-associated 

outpatient visits compared to all infants in the US.14 Native American and Alaskan Natives 

experience cyclical outbreaks due to serotype 12F, which is not included in PCV13 or PCV15.15

Black children continue to have higher IPD rates compared to white children. The remaining 

disparity is mainly due to IPD caused by serotypes that are not included in PCV13. Unpublished 

data from CDC’s ABCs data show that the difference in IPD incidence due to the 2 additional 

serotypes included in PCV15 but not in PCV13 has been small between Black and White.

13 Littlepage et al, 9th International Meeting on Indigenous Child Health, 2021 14 Singleton et al. PIDJ 2018 15 Zulz et al. JCM 2012
ACIP Meeting Summary June 22-23, 2022

39

During the February 2022 ACIP meeting, the WG’s interpretation for this domain was presented 

as “probably increased equity. After further discussion, the WG’s interpretation was changed to 

“probably no impact.” While disparities in pneumococcal disease burden exist, the proportion 

due to the 2 additional serotypes due to PCV15 was considered to be small. Some WG 

members noted that a differential PCV15 and PCV15 update may potentially lead to differences 

in the burden of pneumococcal disease caused by the 2 additional serotypes.

The last domain is feasibility. The current private section PCV15 price for adults is $216.086 

and the PCV13 price for children is $226.43. PCV15 private sector price for adults is currently 

lower compared to that of PCV13 in children. However, the actual PCV15 price that will be used 

for children is currently unknown. Considering that PCV15 is likely to be priced similar to PCV13 

and since PCV13 has achieved high coverage, the WG determined that recommending PCV15 

as an option for pneumococcal conjugate vaccination according to currently the recommended 

dosing and schedule for children is probably feasible to implement.

To summarize the WG’s updated interpretation of the EtR domains for the 2 PICO questions, for 

benefits and harms the WG believes that there are small undesirable effects from PCV15 

compared with PCV13 use, and the overall certainty of evidence on safety is low due to 

imprecision. Balancing the desirable and undesirable effects from PCV15 use compared with 

PCV13 use, the WG believes that both PCV15 and PCV13 use in children is favorable. The 

WG’s interpretation on equity was changed to “probably no impact” given that existing 

disparities in pneumococcal disease burden caused by the 2 additional serotypes is probably 

small. For the new domains presented during this session, the WG believed that PCV15 use is 

probably an acceptable, reasonable, or efficient allocation of resources and is feasible 

compared with PCV13 use. In summary, the WG believes that the balance between desirable 

and undesirable consequences is closely balanced for both policy questions. The WG’s 

proposed policy statement for PCV15 use in children is:

“PCV15 may be used as an option to PCV13 for children aged <19 years according to 

currently recommended PCV13 dosing and schedules.”

Discussion Summary 

Dr. Loehr pointed out that his experience with these recommendations was that there is often a 

delay in when the recommendations are actually practically usable in a private practice. Though 

specifically when there is something like the hepatitis B recommendations given to all adults, it 

would need to be published in the Morbidity and Mortality Weekly Report (MMWR). He then 

finds that it takes 6 months or so before insurance companies will actually start covering them. 

This has nothing to do with pneumococcal per se, but was just a general comment that ACIP 

recommendations sometimes take months before they actually can be implemented in private 

offices.

Dr. Lee noted that the wording on the ACIP policy statement was somewhat more permissive 

and there were many pieces of the presentation. She was swayed by the economic analysis 

that might suggest that perhaps a preference was discussed. She requested a reminder of the 

WG’s discussion of the pros and cons.
ACIP Meeting Summary June 22-23, 2022

40

Dr. Kobayashi indicated that the WG did not consider a preferential recommendation because of 

the uncertainties that exist. That is primarily reflected in the assessment of benefits and harms. 

The current assumption used in the economic analysis is that PCV15 may be priced lower, but 

again that is an assumption, and the actual vaccine price is not known. Additionally, in terms of 

the incremental benefit, the assumptions were based on available immunogenicity studies. 

There currently are no clinical efficacy data and there are uncertainties about the potential 

incremental benefits. Dr. Banniettis presented additional safety data, which was very helpful. 

However, there were still some concerns about uncertainties around some rare AEs. All of those 

issues considered, the WG believes that rather than a preferential recommendation, 

recommending PCV15 as an option might be more appropriate in this situation.

Dr. Lee asked Dr. Leidner to comment on whether there was a probabilistic sensitivity analysis 

performed or what types of sensitivity analyses were performed. In thinking about the economic 

analyses and the cost-saving quadrant, that is really helpful, but it depends on the cost of the 

vaccine. If it does not come out as planned, this will be a different conversation. If it is the same 

as the model price, the question would regard how stable that estimate is and what proportion of 

the analyses resulted in that cost-saving quadrant.

Dr. Leidner indicated that both models did perform probabilistic sensitivity analyses. If all of the 

simulation in the Merck model were in the cost-saving quadrant. For the CDC model, he 

recalled a confidence interval measure in which the 2.5% simulation was inside the cost-saving 

quadrant. That was the most expensive simulation for which they saw a result. 

Proposed Recommendations for PCV15 Use in Children

Miwako Kobayashi, MD, MPH (CDC/NCIRD) reviewed the clinical considerations for use of

PCV15 in children, including the proposed guidance for children who have not received either 

PCV13 or PCV15, children previously vaccinated with PCV13 or PCV15, PPSV-23 use for 

children aged 2–18 years who are at increased risk of pneumococcal disease, and recipients of 

hematopoietic stem cell transplant (HSCT). The proposed guidance will be based on the 

existing recommendations for PCV13 use.16

First is the proposed clinical guidance for children who have not received PCV13 or PCV15. 

Either PCV13 or PCV 15 is recommended as a 4-dose series at ages 2, 4, 6, and 12–15 

months. PCV13 and PCV15 can be used interchangeably. Otherwise, the recommended 

number of PCV doses and intervals will remain the same. For children aged 2–6 months, either 

PCV13 or PCV15 can be administered using the current PCV doses and intervals. Everything 

else remains the same. The same changes will be made for infants aged 7–11 months, 12–23 

months, ≥24 months, and children 6–18 years with an immunocompromising condition. 

For children previously vaccinated with PCV13 or PCV15, children with complete PCV

vaccination may receive PCV13 or PCV15 to complete the recommended vaccination series.

The same changes will be made for children aged ≥24 months. For children aged 24–71 months

with underlying medical conditions, changes are proposed to the current language to clarify

confusion among providers on what an incomplete schedule of PCV doses means. For any

incomplete schedule of fewer than 3 doses, a footnote will be included to provide more

explanation of what that means. The footnote states, “Refer to Table 3 for the recommended 

number of PCV doses and schedule before age 24 months. If a child received 2 doses of PCV 

between age 12–23 months, the child has received a complete PCV schedule and does not 

16 MMWR 2010. 59(RR11); 1–18; MMWR 2013. 62(25); 521–524 
ACIP Meeting Summary June 22-23, 2022

41

require additional PCV doses, even though the total number of PCV doses given is 2.” A 

supplemental dose of PCV15 is not indicated for children who have received 4 doses of PCV13 

or another age-appropriate complete PCV13 schedule.

While no changes are being made to the recommended PPSV23 indications or schedule, 

PCV15 is being added as an option to PCV13 for the clinical guidance. The recommendations 

for PPSV23 revaccination for children with immunocompromising conditions will remain the 

same. No changes are being made to the PPSV23 indications for children who have underlying 

medical conditions. However, children with sickle cell disease or asplenia will be added under

children with immunocompromising conditions because children with these conditions are all 

recommended to receive PPSV23 revaccination. The current pneumococcal vaccine

recommendations do not specifically mention recommendations for children who are HSCT 

recipients. However, the Best Practices Guidance of the Advisory Committee on Immunization 

Practices17 currently states that, “Recipients of hematopoietic stem cell transplants (HSCT) are 

recommended to receive 3 sequential doses of PCV followed by a dose of PPSV23 beginning 

3–6 months after the transplant.”

Discussion Summary 

Dr. Sanchez observed that this is very comprehensive and important as clinicians deal with this 

vaccine on a regular basis. It will be interesting moving forward to see the uptake of PCV15, 

particularly since hospitals and healthcare organizations already have PCV13 available. The 

added benefits and potential lower cost than PCV13 would make him more included to use 

PCV15. Intuitively, protection for more serotypes is something everyone wants. PCV20 will be

coming up in the second quarter of 2023, which will be another issue.

Dr. Kotton asked whether there would be further specifications about which vaccine would be 

recommended after HSCT, or if it will just state PCV.

Dr. Kobayashi said that to be consistent with the rest of the recommendations and the current 

proposal is not to make a preferential recommendation, the plan is to keep it as PCV and then

include either PCV13 or PCV15. 

Dr. Kotton expressed her hope that CDC would be able to answer at some point in the near 

future, at least for adults, because this community is left without guidance in the era of PCV20. 

Not to confuse adults with children, but so it would be good to provide clarity at least for the 

children.

Dr. Long emphasized that some things remain unknown. They can say that a certain 

percentage of disease can be reduced with PCV13, PCV15, and PCV15. They do not have the 

same degree of knowledge about the clinical efficacy of how good these vaccines be for these

serotypes. It is known that the antibody response to serotype 3 is higher with this vaccine than 

with 13, but based on discussions with pneumococcal experts, serotype 3 in models may 

require even more antibody than the antibody response that PCV15 can provide. They can only 

deal with the information that they are given. With the information they have they just would say 

there is some oddness about the numbers of temperatures ≥104°F following PCV15 compared

with PCV13. There is not an ability to ask any questions that could be statistically answered 

because of the small number of people and events in the studies, not to mention the 

heterogeneity of the nation and other issues. Why would there be more fever in the second 

week? This is assumed to be related to MMR vaccine, but why would there be more MMR 

17 https://www.cdc.gove/vaccines/hcp/acip-recs/general-recs/immunocompetence.html 
ACIP Meeting Summary June 22-23, 2022

42

vaccine high fever in PCV15 versus PCV13 recipients? This raises the possibility that maybe

recipients do not respond as well to MMR as rapidly and there is more fever from MMR. The 

WG considered what the public would think of trading a very small incremental benefit for high 

fever, febrile seizures, and potentially more fever from MMR vaccine. This is without any clinical 

efficacy. Although ACIP certainly will approve vaccines without clinical efficacy from a bridge, 

the pneumococcal bridge is very shaky to begin with. For this vaccine, the WG did not think a 

preferential recommendation should be made when there is no clinical efficacy.

Dr. Lee acknowledged that this WG has a set of complicated decisions ahead. She requested 

confirmation about whether she understood correctly that a child had not received vaccine by 6 

years of age, they would receive only PPSV-23 and not any conjugate vaccine.

Dr. Kobayashi clarified that the way the current recommendation is written is that a child with 

immunocompromising conditions, CSF, or a cochlear implant who has never received a

pneumococcal conjugate vaccine is recommended to receive a dose of a pneumococcal 

conjugate vaccine followed by PPSV23. Immunocompetent children with chronic heart disease,

lung disease, or diabetes have missed the opportunity to get a pneumococcal conjugate vaccine 

before 6 years of age are not recommended to receive a conjugate vaccine.

Dr. Lee recognized that this group of children is probably small given that vaccination rates are 

generally pretty high, but these recommendations were made a long while back. For simplicity, 

she asked whether the WG ever discussed whether to offer the ability to receive PCV followed 

by PPSV23 for anyone with high-risk conditions, such as those with chronic lung disease, 

chronic heart disease, et cetera and if there was evidence to suggest that this should not be 

done or if it might be considered in the future. Given that pneumococcal recommendations are 

probably the most complex, aside from COVID-19 right now, with the youngest children to 

implement, she was just trying to think of ways to make it easier and also hold to the principles 

of what they are trying to achieve.

Dr. Poehling responded that this raised a very important point since it would be recommended 

once someone is 19 years of age. The WG was working very fast to review data, so they did not 

spend as much time on these questions. However, the point is well-taken. To her knowledge, 

there is no data to say this should not be done and it would be more feasible to include that.

Dr. Kobayashi added that there also is the anticipation of another conjugate vaccine in the near 

future, so the hope was to try to minimize the confusion as much as possible by not making a lot 

of changes to the recommendations. Therefore, the focus was to follow the current

recommendations on pneumococcal conjugate vaccine use and add PCV15 as an option.

Dr. Daley indicated that he was in favor of the approach recommended by the WG and that this 

felt like a time to make an incremental change and given the uncertainty that Dr. Long 

highlighted in terms of some of the important considerations. 
ACIP Meeting Summary June 22-23, 2022

43

Vote: PCV15 Vaccine Use in Children 

Miwako Kobayashi, MD, MPH (CDC/NCIRD) presented the proposed recommendation for 

PCV15 use in children as follows:

“PCV15 may be used as an option to PCV13 for children aged <19 years 

according to currently recommended PCV13 dosing and schedules.”

Motion/Vote: PCV15 Vaccine in Children

Dr. Ault made a motion for ACIP to adopt the recommendation stating that, “PCV15 may be 

used as an option to PCV13 for children aged <19 years according to currently recommended 

PCV13 dosing and schedules.” Dr. Brooks seconded the motion. No COIs were declared. The 

motion carried with 15 affirmative votes, 0 negative votes, and 0 abstentions. The disposition of 

the vote was as follows:

15 Favored: Ault, Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, 

McNally, Poehling, Sanchez, Talbot

 0 Opposed: N/A

 0 Abstained: N/A 

VFC Vote: PCV15 Vaccines in Children 

Jeanne Santoli, MD, MPH (CDC/NCIRD) the purpose of this resolution was to update the

recommendations regarding the use of pneumococcal conjugate vaccines (PCV) to include 

PCV15 as an option. The resolution has 2 components, the PCV component and the PPV23 

component. Both of them have been updated to reflect the inclusion of PCV15. The eligible 

groups for the PCV component of the resolution are unchanged. The table is slightly different in 

that 2 of the categories that were previously in a separate category called “Functional and 

Anatomic Asplenia” were now included under the “Immunocompromised Persons” category.

Otherwise, the table is the same. PCV13 has been replaced with PCV in order to reference 

PCV13 or PCV15. Clarification was added to be clearer about what constitutes an incomplete 

schedule so that the wording is aligned with the ACIP recommendations. The first footnote now 

indicates that PCV13 or PCV15 may be used. A fourth footnote has been added to clarify what 

is meant by the text in the table. Recommended Dosages and Contraindications and 

Precautions were not changed, although the PCV 15 package insert will be added prior to 

posting this resolution. For the PPSV 23 component, the only change in the eligible groups is in 

Table 1, which asl is referred to in this component of the resolution. Again, reference to PCV 

has been updated to be inclusive of PCV15. Recommended Dosages and Contraindications 

and Precautions were not changed. The standard statement is made about published 

recommendations that are incorporated into the resolution by reference if they are published 

within the next 12 months. 
ACIP Meeting Summary June 22-23, 2022

44

VFC Resolution Motion/Vote: PCV Vaccines in Children

Ms. Bahta made a motion for ACIP to adopt the updates to the VFC Resolution

recommendations regarding the use of pneumococcal conjugate vaccines (PCV) for children to 

include 15-valent PCV (PCV15) as an option. Dr. Brooks seconded the motion. No COIs were 

declared. The motion carried with 15 affirmative votes, 0 negative votes, and 0 abstentions. The

disposition of the vote was as follows:

15 Favored: Ault, Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, 

McNally, Poehling, Sanchez, Talbot

 0 Opposed: N/A

 0 Abstained: N/A

Discussion Summary

Subsequent to the vote, Dr. Lee invited ACIP members to make a statement about the rationale 

for their vote and/or to share any additional general comments:

No additional comments were offered.

MEASLES, MUMPS, AND RUBELLA (MMR) VACCINE

Session Introduction

Lynn Bahta RN, MPH (ACIP WG Chair) provided and introduction to the MMR session, 

reporting that the FDA approved the GlaxoSmithKline (GSK) MMR vaccine, Priorix, on June 3, 

2022. Until this month, there has been only one licensed MMR vaccine product in the US, M-MR®II, manufactured by Merck. MMR vaccine is currently recommended for administration at ≥12 

months of age for the prevention of measles, mumps, and rubella and for post-exposure

measled prophylaxis. Additionally, MMR is recommended for off-label use in 2 situations. The 

first situation is for infants 6 through 12 months of age planning to travel or live abroad or during 

outbreaks.18 The second situation is for a third dose in previously vaccinated persons with 2 

doses who are identified as being at increased risk because of a mumps outbreak.19 Since 

January 2022, the MMR Vaccine WG has been meeting to evaluate the safety and

immunogenicity of Priorix as compared to M-M-R®II. The WG has been led by Dr. Elizabeth 

Krow-Lucal who has championed efficiency to bring them to this day for a proposed 

recommendation and vote. 

Priorix for Prevention of Measles, Mumps, and Rubella

Elisabeth Krow-Lucal, PhD, MPH (CDC/NCIRD) presented the EtR Framework and literature 

review on Priorix for the prevention of measles, mumps, and rubella on behalf of the MMR 

Vaccines WG workgroup. The policy question for this review was, “Should MMR vaccine, Priorix 

manufactured by GSK, be recommended as an option according to currently recommended

schedules and off-label uses to prevent measles, mumps, and rubella?” The population is 

18 https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6204a1.htm 19 https://www.cdc.gov/mmwr/volumes/67/wr/mm6701a7.htm 
ACIP Meeting Summary June 22-23, 2022

45

persons ≥6 months of age. The intervention is GSK’s Priorix. The comparator is the existing 

MMR vaccine licensed in the US, M-M-R®II, manufactured by Merck. The outcomes of interest 

are prevention of measles, mumps, and rubella; short-term humoral immunity; persistence of 

the humoral immune response; reactogenicity Grade ≥3; and SAEs of interest identified by 

ACIP and the WG (e.g., febrile seizures, aseptic meningitis, and immune thrombocytopenic 

purpura).

As previously presented to ACIP, Priorix was first licensed in Germany in 1997. It has been 

approved in over 100 countries outside of the US and over 400 million doses have been 

distributed worldwide. Countries where Priorix has been approved include all European

countries, all European Union countries, Canada, Australia, and many others worldwide.

It also has been prequalified by WHO. Priorix is currently registered in 97 countries. Priorix is 

considered fully interchangeable with M-M-R®II or M-M-RVaxPro in a number of countries. Both

vaccines contain live-attenuated measles, mumps, and rubella viruses. M-M-R®II and Priorix 

contain the same strains for mumps and rubella and a similar lineage of measles. Both of the 

measles and rubella strains found in M-M-R®II and Priorix are 100% identical on a nucleotide 

level. The Jeryl LynnTM strain used in the mumps component of M-M-R®II is a mixture of 2 viral 

lineages, JL1 and JL2. RIT4385, the mumps component from GSK, is a pure clone of JL1 and is 

100% identical on a protein level to Merck’s JL1 component. For differences in inactive

ingredients, M-M-R®II contains porcine gelatin and Priorix does not. This table shows the 

minimum and maximum potencies for M-M-R®II and Priorix in the US:

According to FDA’s requirements for live viral vaccines, minimum and maximum viral potency 

titers for Priorix were defined during clinical development to ensure efficacy at minimum potency 

and an acceptable safety profile at maximum potency. The lines show the range from minimum 

to maximum potencies for M-M-R®II in orange and Priorix as licensed in the US in purple. GSK 

will be changing the dosage for all countries to align with the US dosage.

No turning to the EtR Framework beginning with the public health problem, attaining and

maintaining high, 2-dose MMR coverage has led to measles and rubella elimination in the US

and low levels of mumps. Despite high 2-dose vaccine coverage, measles and mumps continue 

to cause locally acquired and importation-related cases and outbreaks. Given this, the WG is of 

the opinion that the prevention of these diseases is a problem of public health importance.
ACIP Meeting Summary June 22-23, 2022

46

In terms of the domain of benefits and harms and how substantial the desirable and undesirable 

anticipated effects are of Priorix compared with currently used M-M-R®II, the WG conducted a 

literature review to assess the safety and immunogenicity of Priorix. Studies in any language 

were identified from PubMed, Embase, CINAHL, Cochrane, Scopus, and clinicaltrials.gov

databases using the following search string:

 “Measles-Mumps-Rubella Vaccine” 

 And (“Priorix” or “MMR vaccine” or (“GlaxoSmithKline*” or “GSK”) and “MMR*”) or “GSKMMR” or “MMR-RIT” or “SB-MMR”)

 And “Safe*” or “effective*” or “efficacy” or “immun*” or “interchangeab*” or “inter-changeab*” 

or “adverse” or “M-M-R II” or “Merck” or “evidence*” or (“review” or “meta*”)

Results were limited to RCTs or systematic reviews and meta-analyses. Of the 918 studies

identified, 18 were relevant to the PICO question. Of those, 16 were RCTs that compared 

Priorix and M-M-R®II head-to-head, and 2 were systematic reviews that included Priorix-specific 

information. An additional 5 studies with a different study design or comparator vaccine also 

were reviewed for safety data on the conditions of interest identified by the WG and ACIP. For 

safety data, the WG focused on the 4 RCTs using a licensed US dose and 2 reviews and 5 

studies with different designs or dosages to assess specific safety conditions indicated in

February by ACIP. In terms of the characteristics of the 4 RCTs using the licensed US dose, the 

majority (90%) were conducted in the US. Approximately 68% received Priorix and 32% 

received a first dose of MMR. There was no significant difference in race and ethnicity between 

the Priorix and M-M-R®II groups. None of the studies examined prevention of disease directly. 

All 4 reported SAEs and reactogenicity of Grade 3 or higher. All studies used a comparator 

vaccine, as it would be unethical to compare against placebo alone in this situation.

From these studies and studies previously presented to ACIP, Priorix shows a similar safety 

profile to M-M-R®II. Follow-up time in these studies was from 40 days to 6 months post-MMR 

vaccination. The frequency of vaccine-related SAEs was low, ranging from 0% to 0.2% for the 

Priorix group and 0% to 0.03% in the M-M-R®II group. Vaccine-related SAEs identified in clinical 

trials were immune thrombocytopenic purpura in 1 participant each in the M-M-R®II and Priorix 

groups, inguinal adenitis in 1 Priorix participant, and 1 complex febrile seizure in an M-M-R®II

participant. Additional safety information was collected from the literature based on questions 

from ACIP and WG members on conditions of interest indicated in February by ACIP including 

febrile seizures, aseptic meningitis, and immune thrombocytopenic purpura (ITP) compared to 

the current M-M-R®II vaccine. Because these events are very rare, it is difficult to identify this 

risk in the RCTs. For that reason, the WG looked more broadly in the literature.

The rate of febrile seizures is highest in the 6 to 11 days following vaccination for all MMR 

vaccines. The rate of febrile seizures in this period is estimated to be 3.3 to 8.7 per 10,000 

doses based on 2 studies conducted in the UK that which included both Priorix and M-M-R®II.20

From the clinical trials data provided by GSK and presented to ACIP in February, at the target 

minimum and maximum potencies, the rate of febrile seizures in the Priorix group was 9.5 per 

10,000 doses in approximately 8,300 children studied and 14.8 per 10,000 doses in 

approximately 3,500 children studied. All studies included age-appropriate vaccine coadministration and all studies found the differences in rates of febrile seizures to be nonsignificant between the 2 vaccines. Similarly, the time-course of fever was comparable for both 

vaccines across all studies, with the majority of instances observed 5 to 12 days postvaccination.

20 Miller, E. et al. Risks of Convulsion and Aseptic Meningitis following Measles-Mumps-Rubella Vaccination in the United Kingdom. 

Am J Epidemiol 165, 704–709 (2007); and Farrington, P. et al. A new method for active surveillance of adverse events from 

diphtheria/tetanus/pertussis and measles/mumps/rubella vaccines. Lancet 345, 567–569 (1995)
ACIP Meeting Summary June 22-23, 2022

47

The second issue raised was aseptic meningitis. While this has not been studied in an RCT, a 

paper from 2007 in the UK used active surveillance to identify aseptic meningitis and mumps 

meningitis in the 15 to 35 days post-vaccination from 1998 to 2004.21 This was a comparison to 

the rate of the previously licensed vaccine in the UK, which contained the Urabe Am 9 strain of 

mumps, which is known to be associated with aseptic meningitis. There 2 case definitions used

for aseptic meningitis, ICD-9 and 10 codes and chart review for aseptic meningitis and

laboratory-confirmed mumps meningitis cases. In this time period, 0 cases of aseptic meningitis 

were identified from ICD-9 and 10 code and chart review out of 99,177 doses of Priorix given, 

and 0 cases of laboratory-confirmed mumps meningitis were identified out of approximately 1.6 

million doses of Priorix given. Based on the number of doses and cases observed in the

timeframe, risks as rare as 1 in 437,000 doses could be excluded for Priorix. Additional doses 

would need to be observed to rule out rarer risks. In addition, the WHO Global Advisory 

Committee on Vaccine Safety (GACVS) did not find any cases of virologically proven aseptic 

meningitis following Jeryl Lynn vaccination.22 The most recent Cochrane Review from 202123

states that there is no evidence of association between aseptic meningitis and vaccines 

prepared with the Jeryl-Lynn strains, which includes RIT 4385, the mumps component found in 

Priorix.

The third condition of interest was ITP, which is associated with the receipt of live-attenuated 

measles vaccines. There is very limited brand-specific data available on ITP. From the 4 RCTs 

at the US dosage of Priorix, there was 1 case each in the Priorix and M-M-R®II groups. By 

comparison, for M-M-R®II a VSD study reported a rate of 2.5 cases per 100,000 doses.24 In the 

literature, data is available from three studies and a Cochrane Review. All show an association 

with ITP. However, the case definitions varied across papers. ITP is a very rare event and when 

examining vaccine-specific events, the denominator is small. This leads to large confidence 

intervals and uncertainty around the point estimates of rate ratios. Based on the limited 

estimates available, the best interpretation is that the rates and rate ratios for M-M-R®II versus 

Priorix are not different from each other.

In summary of the conditions of interest, there was a similar rate and severity of febrile seizures 

after vaccination with Priorix or M-M-R®II. There is no evidence of association of aseptic

meningitis with vaccines prepared Jeryl-Lynn strains and risks as rare as 1 in 437,000 doses 

can be excluded. Based on limited data available, there were similar rates of ITP after

vaccination with Priorix or M-M-R®II.

To review the available information on immunogenicity of Priorix compared to M-M-R®II, of the 

16 RCTs, 13 had immunogenicity data. Of these, 4 were of the licensed US dose and 9 were at 

a lower Priorix dose. All were reviewed for measles, mumps, and rubella seroconversion after 

first or second dose, as well as GMC after the first or second dose. All studies showed a GMC 

well above the estimated correlate of protection. Of the 13 RCTs reviewed, 12 showed no 

difference in anti-measles GMC. Unlike measles, mumps does not have a known correlate of 

protection. Seropositivity is defined as ≥10 EU/mL. All studies demonstrated that both vaccines 

exceeded the minimum threshold, and 10 of 13 studies showed no statistically significant

21 Miller, E. et al. Risks of Convulsion and Aseptic Meningitis following Measles-Mumps-Rubella Vaccination in the United Kingdom. 

Am J Epidemiol 165, 704–709 (2007) 22 World Health Organization Global Advisory Committee on Vaccine Safety. WER 32, 282–283 (2003) 23 DiPetrantonj C, et al. Vaccines for measles, mumps, rubella, and varicella in children. Cochrane Database of Systematic Reviews 

2021

24 France, E. K. et al. Risk of Immune Thrombocytopenic Purpura After Measles-Mumps-Rubella Immunization in Children. 

Pediatrics 121, e687–e692 (2008). 
ACIP Meeting Summary June 22-23, 2022

48

difference between anti-mumps GMC levels. The rubella correlate of protection is estimated to 

be 10 IU/mL. All studies demonstrated that both vaccines exceeded this threshold, and 12 out of 

13 studies showed no statistically significant difference between Priorix and M-M-R®II. 

In summary of immunogenicity, of the studies conducted with the US dosage, there was no 

significant difference between Priorix and M-M-R®II GMC for measles, mumps, or rubella. Of the 

studies conducted at a lower dosage than the US, all studies show GMC higher than the

correlate of protection for both measles and rubella and the seroresponse threshold for mumps. 

Of 13 studies, 10 showed no statistically significant difference between anti-mumps GMC levels.

There was no significant difference for second dose between Priorix and M-M-R®II for measles, 

mumps, or rubella GMC levels at any potency.

To summarize the benefits and harms domain, the WG considered that the difference in both 

the desirable anticipated effects and the undesirable anticipated effects of Priorix compared

with M-M-R®II were minimal and the balance between the vaccines favored both.

Regarding the feasibility domain and whether Priorix as an option for MMR vaccination is

feasible to implement and the acceptability domain in terms of whether Priorix acceptable to key 

stakeholders, between 2000 and mid-2003,25 the US experienced occasional shortages of a 

number of routinely recommended vaccines, including MMR. These shortages were due to 2 

voluntary interruptions to manufacturing operations by Merck,26 both of which took longer to 

resolve than anticipated and that were significant enough that the ACIP recommendations had 

to be temporarily modified, including suspension of the second dose of MMR in cases of 

insufficient vaccine quantities. Redundancy in supply is a critical component of sustainable 

public health.27 An important point to note here is that MMRV, MMR, and varicella combination 

vaccine account for roughly 13% (5% to 24%) of first doses and roughly 80% (52% to 98%) of 

second doses in this childhood vaccine series.28 Given this, the WG considered that an 

additional MMR vaccine (Priorix) that is safe and not inferior to the existing MMR vaccine (M-MR®II) could be beneficial in maintaining measles and rubella elimination and mitigating mumps 

outbreaks in the US, as well as assuring supplier diversity.

To assess feasibility and acceptability, the WG conducted a focus group with state health

department Immunization Managers to identify potential barriers to Priorix. Participants noted 

that the majority of VFC and vaccine programs order based on providers’ demand and that this 

is the main factor driving new vaccine adoption. Adding Priorix into the routine immunization

system, vaccine access, distribution, storage and handling, and implementation of 

communication and education strategies were not considered barriers. Participants welcomed 

the idea of having another brand available in case of outbreaks or manufacturing interruptions.

In addition, 1 participant noted the benefit of having a gelatin-free vaccine (Priorix) for religious 

populations with objections to gelatin. A survey also was conducted of 400 pediatricians and 

400 family medicine practitioners. Participants were asked a number of questions,

including about their current MMR vaccination practices and barriers to having a second MMR 

product. The key findings from the survey as related to feasibility were concerns about the 

possibility of not being able to mix and match doses. A quarter of participants reported having 

25 Santibanez TA, et al. Differential Effects of the DTaP and MMR Vaccine Shortages on Timeliness of Childhood Vaccination 

Coverage. American Journal of Public Health. 2006

26 Shortage of varicella and measles, mumps and rubella vaccines and interim recommendations from the Advisory Committee on 

Immunization Practices. MMWR Morb Mortal Wkly Rep. 2002

27 Shortage of varicella and measles, mumps and rubella vaccines and interim recommendations from the Advisory Committee on 

Immunization Practices. MMWR Morb Mortal Wkly Rep. 2002

28 Executive Order 14001 “On a Sustainable Public Health Supply Chain” 

https://www.phe.gov/Preparedness/legal/Documents/National-Strategy-for-Resilient-Public-Health-Supply-Chain.pdf 
ACIP Meeting Summary June 22-23, 2022

49

patients who did not receive an MMR vaccine due to allergy to a vaccine component. Of those, 

30% to 40% reported that the allergy was to gelatin, and the majority of pediatricians had used 

the MMR vaccine for patients under the age of 1 year.

The major categories identified were concerns that the vaccines were not fully interchangeable,

including off-label usage and a potential benefit for a gelatin-free vaccine to serve potentially 

allergic patients. Given the concerns identified around interchangeability in the survey, the WG 

looked at the available evidence for interchangeability. Previously presented studies showed

non-inferior responses and similar safety profiles for individuals receiving a first dose with M-MR®II, or ProQuad® (MMRV) and a second dose of Priorix. A number of countries (e.g., Australia, 

Canada, Denmark, France, New Zealand, the UK, Ireland, and others) consider Priorix and MM-R®II or M-M-RVaxPro to be fully interchangeable. In addition, both the FDA and the European 

Medicines Agency (EMA)29 allow for vaccination with Priorix in individuals who have previously

been vaccinated with a different MMR vaccine. However, there are limited data on the 

interchangeability for those who receive Priorix as a first dose, followed by M-M-R®II or

ProQuad®. There were no safety or immunogenicity differences identified in the available data

as expected, given the vaccine component similarity.30

In summary, the WG considered that Priorix is acceptable to key stakeholders and feasible to 

implement. However, the WG is of the opinion that differences in off-label uses and

interchangeability recommendations could negatively affect the acceptability and feasibility. MM-R®II and Priorix will have the same VFC price. Given this and the similarities in formulation 

and storage, the WG considered that there would probably be no impact on health equity for 

Priorix as compared to M-M-R®II. Finally, the WG considered that the values and resource use 

based on similarities of schedule, anticipated harms and benefits, and VFC costs.

The 2 vaccines are comparable, with values and resource use similar to that of M-M-R®II. Based 

on EtR considerations, Priorix and M-M-R®II vaccines are closely balanced. Therefore, the WG 

judgment on adding Priorix as an option for MMR vaccination is as follows. The desirable 

consequences clearly outweigh the undesirable consequences in most settings. Given the

similarities in dosage, vaccine components, evidence from the clinical trials, and literature 

review, the WG considers that Priorix and M-M-R®II should be considered fully interchangeable, 

including all off-label uses and may be administered in any situation in which a measles-, 

mumps-, and rubella-containing vaccine is indicated.

Discussion Summary

Dr. Long asked in the 400 million doses and 100 countries, how many other countries give 

varicella vaccine concurrently with the first dose of Priorix and if there are any data on that. She 

also inquired about AEs with the concurrent boatload of vaccines given to children at the time 

they are given their first MMR and whether there are any data on PCV, DTaP, and Hib in the 

beginning of the second year of life. 

Dr. Krow-Lucal responded that all of GSK's clinical trials used the routinely given vaccinations in

those age groups, including varicella, hepatitis A, and PCV13 in the US studies.

29 https://www.ema.europa.eu/en/documents/referral/priorix-article-30-referral-annex-iii_en.pdf 30 Abu-Elyazeed, R. et al. Immunogenicity and safety of a second dose of a measles-mumps-rubella vaccine administered to healthy 

participants 7 years of age or older: A phase III, randomized study. 2018. and personal communication 2022
ACIP Meeting Summary June 22-23, 2022

50

Dr. Friedland, Medical Affairs Team at GSK Vaccines, thanked the CDC, the ACIP, and the

members of the ACIP MMR WG for their evidence-based review of GSK’s US-licensed MMR 

vaccine, Priorix. Before the CDC implemented a measles vaccination program in 1963, an

estimated 3 to 4 million people got measles each year in the US. Since then, CDC’s highly 

successful public health program resulting in widespread use of measles virus-containing

vaccine has led to a greater than 99% reduction in measles cases compared with the prevaccine era. Recent US measles outbreaks and mumps cases highlight the importance of 

maintaining high vaccination rates to ensure control of the diseases. The availability of a second 

MMR vaccine in the US could help mitigate some of this public health risk. This past April, a

CDC report noted 400,000 fewer children entered kindergarten in the 2020-2021 school year 

than expected nationally, meaning those children may not be up-to-date on childhood

immunizations. The availability of a second MMR vaccine in the US will ensure health care 

professionals have more than one MMR option as they work to catch their patients up on

recommended vaccinations. Data across 5 Phase 3 clinical trials and rolling over 16,000 

children and adults demonstrate that Priorix is immunologically non-inferior to M-M-R®II and has 

a comparable safety profile. The FDA licensed Priorix on June 3, 2022. Based on FDA’s review 

of the clinical trial results and use outside the US, there are no post-marketing commitments or 

requirements. The ACIP’s recommendations and clinical guidance are crucial for providing

clarity for providers on the appropriate use of the vaccine. Given the immunological and safety 

profile of Priorix, the committee’s and center’s clinical expertise and knowledge of MMR disease 

and immunization, GSK asks the ACIP to support the use of Priorix in the same routine catch-up 

and special situations for MMR disease prevention and control as with M-M-R®II. On behalf of 

all of his GSK colleagues, they are proud to bring an additional MMR vaccine option for 

providers and patients in the US.

Dr. Long asked whether there is a combined prior varicella vaccine that would be acceptable to 

children 4 to 6 years of age, referring to the comment that this vaccine could be substituted

when MM and R are required. She recalled that ACIP’s previous recommendation was a

preference for MMRV as the second dose to reduce numbers of injections. If MMRV is preferred 

over MMR plus V at 4 to 6 years of age, this vaccine would not be preferred for the second

dose. She wondered whether ACIP would need to say something about MMR plus V and if this 

vaccine for the second dose, whether it would require 2 injections.

Dr. Krow-Lucal indicated that there is an MMRV vaccine, Priorix-Tetra, that is licensed outside 

of the US. She did not have any information on whether GSK will bring that to the US. In terms 

of the question on the recommendation for MMRV as compared to MMR, as noted from the 

information they were able to get from their immunization colleagues, a majority of second

doses in the US are given as MMRV.

Dr. Mona Marin added that MMRV is preferred for the second dose because it is part of the 

preference given to combination vaccines. It is not based on any immunogenicity of safety data. 

For the first dose, the recommendation is that providers can give either MMR and varicella or 

MMRV, but they should discuss the option with the parents. If the parents prefer MMRV, they

would give MMRV. Otherwise, the CDC recommendation is to go with separate vaccination 

because of the increased risk for febrile seizures after MMRV for the first dose for young 

children. In this situation, it would be used the same as M-M-R®II. If a provider is going to give 

M-M-R®II as a second dose, this would be an option. If they are giving M-M-R®II alone, then

they would have to do the same for the non-combination vaccine, which is not preferred.
ACIP Meeting Summary June 22-23, 2022

51

Dr. Sanchez said he did not think that the AAP Red Book actually says anything about a 

preference for an MRV at 4 to 6 years of age. Regardless, this needs to be explained to

parents. It certainly is great to have another vaccine available. He asked whether the storage

requirement is the same as M-M-R®II to prevent activation; whether any of the studies looked at 

allergic reactions, which was brought up by the survey in terms of the urticaria and so-called 

allergic reactions to MMR that have been possibly attributed to gelatin; and whether the new 

vaccine is egg-based.

Dr. Krow-Lucal indicated that the difference is that Priorix should be stored refrigerated, not 

frozen, but that is similar to other routinely given vaccinations. To caveat the survey results in 

terms of allergic reactions, the WG asked only if a vaccination had been declined because of an 

allergy. They did not ask if it was a clinically-verified allergy. Of those in the survey, the WG 

does not have a good understanding of how many would be true allergies to be concerned 

about. In terms of the differences in potential allergic reactions, limited data are available and 

were not looked at in the clinical trials. There is literature primarily from Japan looking at the 

removal of gelatin from all vaccines that could be of interest, but it was not specifically looked at 

in these trials. The new vaccine, Priorix, is egg-based.

Dr. Kimberlin, AAP Red Book Editor, indicated that the Red Book on MMRV versus MMR plus 

varicella vaccine reads as follows, “Either MMRV or separate MMR and varicella vaccines are 

acceptable options for Dose 1 at 12 through 15 months of age. Pediatricians should discuss 

risks and benefits of the vaccine choices with the parents or caregivers. For the first dose of 

measles, mumps, rubella, and varicella vaccine at ages 48 months and older and for Dose 2 at 

any age 15 months through 12 years, use of MMRV vaccine generally is preferred over 

separate injections in MMR and varicella vaccines to minimize the number of injections.”

Referring to Slide 17, Dr. Brooks asked whether aseptic meningitis was found in Priorixvaccinated individuals only, or if it also was found in M-M-R®II. Referring to Slide 23, he noticed 

that there were confidence intervals for the 4 US studies, but not the others above that.

Dr. Krow-Lucal indicated that the study to which Dr. Brooks referred was conducted in the UK. 

Prior to this, the vaccine that was licensed in the UK contained the Urabe Am 9 strain of 

mumps, which has been associated with aseptic meningitis. When that was replaced with 

Priorix, there was an interest in making sure that Priorix specifically was not associated with 

aseptic meningitis. This study was Priorix-specific and the paper was comparing to the previous 

Urabe Am 9 strain. The studies do have confidence intervals, but given the scale and the range

of the differences, they were obscured.

In terms of the proposed recommendation language and based on what Dr. Kimberlin read, Dr. 

Long asked whether ACIP needed to state someplace that there currently is no combination 

MMRV vaccine. It seemed to her that families would need to be informed that they would have 

to get the V in another injection. Doctors may have one or the other vaccine in their offices. If a 

combination vaccine is preferred for the second dose, the doctor would have to tell the family 

that their child would need 2 injections at 4 to 6 years instead of 1 versus saying they got a 

better deal on the GSK vaccine, for example.

Dr. Krow-Lucal said this is something that could be included in the Clinical Considerations. This 

is not being recommended as a replacement for MMRV, merely as an additional option. Having 

that language available that MMRV is preferred will still be in place.
ACIP Meeting Summary June 22-23, 2022

52

Ms. Bahta thought they should go back to the focus of the language that this is a vaccine that 

can be used interchangeably with M-M-R®II and that all of the rules and the recommendations 

would apply. That would include a provider using a combination vaccine. They already have to 

have that conversation if they are using separate or combined. Therefore, she thought they 

should stay relevant to the proposed language.

Dr. Poehling agreed and highlighted that large health systems do receive better deals if they

use predominantly one or another product by a manufacturer. She emphasized the importance

of giving providers the freedom to use products from different manufacturers. 

Vote: MMR Vaccine 

Elisabeth Krow-Lucal, PhD, MPH (CDC/NCIRD) presented the following proposed 

recommendation for influenza vaccine:

“The MMR vaccine, Priorix, is recommended according to currently recommended 

schedules and off-label uses as an option to prevent measles, mumps, and rubella.”

Motion/Vote: MMR Vaccine

Dr. Poehling made a motion for ACIP to adopt the recommendation stating that, “The MMR 

vaccine, Priorix, is recommended according to currently recommended schedules and off-label 

uses as an option to prevent measles, mumps, and rubella.” Dr. Talbot seconded the motion.

No COIs were declared. The motion carried with 15 affirmative votes, 0 negative votes, and 0 

abstentions. The disposition of the vote was as follows:

15 Favored: Ault, Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long,

McNally, Poehling, Sanchez, Talbot 

 0 Opposed: N/A

 0 Abstained: N/A

 0 Absent: N/A

Discussion Summary

Subsequent to the vote, Dr. Lee invited ACIP members to make a statement about the rationale 

for their vote and/or to share any additional general comments:

Patsy Stinchfield (NAPNAP) first noted that she serves on the Influenza, MMR, and RSV WGs 

and wanted to publicly thank the CDC staff and point out that the work behind the scenes is 

phenomenal. The amount of rigor in the EtR Framework and the respect, thoroughness, and 

inclusiveness of those who are not part of the CDC are really commendable. She just wanted 

everyone in the vaccine arena of CDC to know how much they are valued. Second, she 

stressed that having an additional MMR option is very good. However, they must put these 

vaccines to use. MMR vaccine coverage rates in the US already were low before the pandemic 

and have been decreasing for a number of reasons, misinformation being one of them. She is 

very concerned about our next outbreak being measles. They have seen 2 cases in Minnesota, 

including a hospitalized child after international travel. She encouraged everyone to ensure that 

they are conducting remind/recall to get children vaccinated.
ACIP Meeting Summary June 22-23, 2022

53

HUMAN PAPILLOMAVIRUS (HPV) VACCINE

Session Introduction

Lauri E. Markowitz, MD (CDC/NCIRD) gave a brief introduction to the human papillomavirus 

(HPV) vaccine session, explaining that the purpose of this session was to provide an overview 

of evidence on 1-dose HPV vaccination; summarize updated recommendations of the World 

Health Organization’s (WHO’s) Strategic Advisory Group of Experts on Immunization (SAGE)

that were made in April 2022; and provide a brief update on HPV vaccination coverage and 

impact of the US HPV vaccination program. Given that the last presentation to ACIP on HPV 

vaccine was in 2009, Dr. Markowitz began with a short background overview.

All currently available HPV vaccines are virus-like particle (VLP) vaccines. These VLPs selfassemble spontaneously from 72 pentamers of the L1 major capsid protein expressed using 

recombinant technology. Because they are produced from a single virion protein, they are noninfectious and non-oncogenic. These VLPs are morphologically similar to authentic virus and

induce high levels of neutralizing antibodies. There are 3 vaccines licensed in the US show in 

this table:

All 3 vaccines target 16/18 HPV types that cause most HPV-attributable cancers. The 

quadrivalent and 9vHPV vaccines also target 6/11 types that cause most genital warts. The 

9vHPV vaccine targets 5 additional cancer-causing types. All of these vaccines have been 

found to have very high efficacy against vaccine targeted types. The quadrivalent vaccine was 

the first license in the US in 2006, followed by bivalent in 2009, and 9vHPV in 2014. Before 

2015, almost all vaccine use in the US was the quadrivalent vaccine. Since the end of 2016,

only the 9vHPV vaccine has been available in the US. All of these vaccines are available in 

other countries.

In the US, HPV vaccination was recommended in 2006 for females. At that time, HPV vaccine 

was only licensed in females and routine vaccination was recommended for persons 11-12

years of age. The series can be started at 9 years of age and catch-up was recommended

through 26 years of age. In 2011, routine vaccination of males 11-12 years of age was

recommended, with catch-up through 21 years of age. Vaccination was first recommended as a 

3-dose schedule. In 2016, a 2-dose schedule was recommended for those starting vaccination

before 15 years of age. In 2019, catch-up vaccination was harmonized through 26 years of age

for everyone. Also in 2019, a recommendation was made for shared clinical decision-making for 

persons 27 through 45 years of age. The current recommendations for HPV vaccination include 
ACIP Meeting Summary June 22-23, 2022

54

routine, catch-up and shared clinical decision-making. The number of doses depends upon the 

age the series is initiated, with 2 doses recommended for those starting the series before 15 

years of age.31

National and State-Level HPV Vaccination Coverage

Shannon Stokley, DrPH (CDC/NCIRD) discussed adolescent vaccination coverage levels, the 

impacts of the COVID-19 pandemic on routine vaccination, and efforts to increase routine

vaccination. CDC monitors adolescent vaccination coverage through the National Immunization 

Survey-Teen (NIS-Teen). This is a cellphone-based survey of parents of adolescents 13

through 17 years of age. With consent from parents, the vaccination histories of adolescents are 

obtained from the medical provider and there are estimates based on medical records and not 

parental recall. Looking at trends in vaccination coverage from 2006-2020,32 the most recent 

year of data available, nationally vaccination coverage for Tdap or Meningococcal vaccination 

was high at about 90%. This is much higher than coverage for the first dose of HPV vaccine of

75% and coverage for the HPV series of 59%. Although coverage for HPV is lower than other

routinely recommended vaccines, it did continue to increase each year—even in 2020.

In terms of estimated vaccination coverage with at least 1 HPV vaccine, there is wide variation

in coverage across the country that ranges from 55% in Mississippi to 93% in Rhode Island. 

Coverage is typically lower in the Southeast. Coverage for the HPV series ranges from 32% in 

Mississippi to 83% in Rhode Island and a similar pattern emerges with lower coverage in the 

Southeast. Since the HPV vaccine has been licensed and introduced, an interesting pattern has 

been observed in vaccination coverage by race/ethnicity. Consistently over time, vaccination

coverage has been higher for Hispanic and non-Hispanic Black adolescents compared to nonHispanic White adolescents. It is not clear what may be driving these differences, but the 

pattern holds whether evaluating initiation of a series or series completion. Differences are also 

seen in vaccination coverage by urbanicity, with vaccination coverage consistently being lower

for adolescents living in rural areas by about 12 percentage points. This difference appears to 

be narrowing in the most recent years of data, but vaccination coverage for adolescents living in 

rural areas increases at the same rate as those living in urban areas. It is just much lower than

in the urban population.33

In summary, high vaccination coverage for Tdap and meningococcal vaccines continue to be 

seen. While HPV vaccination is lower, it continues to increase. Differences in coverage continue 

to be seen by race/ethnicity and by metropolitan statistical area (MSA) or urbanicity.

In terms of the impact of the COVID-19 pandemic on adolescent vaccination, the past 2.5 years 

have been difficult on many and routine vaccination is no different. There were disruptions in

health care services in 2020, some of which may continue. The results of the NIS-Teen for 2020

were somewhat surprising in that a drop in coverage was not seen. However, the 2020 survey

was not able to assess the impact of the pandemic because most of the teens included in the 

survey had started the vaccination series prior to the pandemic. While the survey includes teens 

13 through 17 years of age, it measures vaccination received at any point in their lives. 

Therefore, most of these teams started the HPV series before 2020. Additional years of data are 

needed to truly assess the impact of a pandemic. CDC is just now receiving the data from 2021 

survey, which should be available later this year.

31 Recommendations of the Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices 

https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/hpv.html 32 https://www.cdc.gov/mmwr/volumes/70/wr/mm7035a1.htm 33 https://www.cdc.gov/vaccines/imz-managers/coverage/teenvaxview/index.html 
ACIP Meeting Summary June 22-23, 2022

55

Absent survey data, another way the impact of the pandemic on routine vaccination can be 

assessed is by monitoring vaccine orders for the Vaccines For Children (VFC) Program. The 

VFC program provides vaccines at no cost for children who otherwise would not be able to

afford vaccinations. In the US, about 50% of children receive their vaccines through the VFC 

program. Vaccine orders are monitored by fiscal year (FY), which aligns with the school year 

running from October 1 through September 30. In terms of VFC provider orders for HPV vaccine 

for FY 2019 through 2022. Using FY 2019 as the baseline, total orders decreased about 24%. In 

FY 2020 and FY 2021, there was improvement in total orders, but they were still about 9% lower 

than 2019. In terms of year-to-date orders for 2022, orders are about 10% lower than the same 

time period in 2019.

Another way the impact of a pandemic can be evaluated is by looking at data from Immunization 

Information Systems (IIS). CDC receives IIS data from 13 jurisdictions. HPV vaccination

coverage was evaluated by age for 2018 through 2021. Coverage for 1 or more HPV vaccines, 

coverage increased slightly in 2020 and 2021 for adolescents 13 years of age and older. Where 

the impact is seen is with persons 11-12 years of age, which compared to 2019 coverage

decreased 3 percentage points in 2020. Coverage continued to decrease in 2021. There were 

slight increases each year for the older adolescent age groups, with a slight decline for persons 

11-12 years of age.

In summary, vaccine orders and vaccine administration have decreased since the start of the 

pandemic, leaving some children unprotected from vaccine-preventable diseases. Based on 

surveys CDC has conducted, parental concerns about potential exposure to COVID-19 may be 

contributing to declines for making well-child visits when vaccines are usually administered. 

Concerted efforts are needed to help children get caught up on vaccines that they may have 

missed during the pandemic. In the coming months, a multifaceted approach will be needed

from all stakeholders to ensure that children get back on track with routine vaccination. CDC 

has launched the “Let’s Play Catch-Up On Routine Vaccines” campaign34 to help with this effort.

Materials available to help promote routine vaccination include a toolkit for providers, social

media messages, and other materials to help promote vaccination. There are some activities in 

which healthcare systems and healthcare providers can engage now, including encouraging

members to identify and follow-up with families whose children have missed doses to schedule

appointments; implement clinician prompts to remind clinicians to review patients’ vaccination 

status during an office visit so they can offer vaccines that are due or overdue; communicate 

directly to families about the importance of well-child visits and routine vaccinations; and let 

families know about precautions that are in place for safe delivery of in-person services.

Discussion Summary

Dr. Goldman (ACP) said he wanted to impress upon the internal medicine community to talk 

about catch-up vaccines. He gives all adult vaccines in his office and routinely asks his patients 

who are 18-19 years of age whether they have received a Gardasil® vaccine. Outreach through 

the internal medicine community offers another opportunity to catch-up those who have not 

been vaccinated for whatever reason in the pediatric setting. He emphasized the important of 

engaging all stakeholders.

34 https://www.cdc.gov/vaccines/partners/childhood/stayingontrack.html 
ACIP Meeting Summary June 22-23, 2022

56

Dr. Daley found the ordering data to be sobering. This means that millions of individuals in this 

age group are unprotected. He asked whether this scope matches with IIS data in terms of the 

number of people who are estimated to have missed their opportunity for HPV vaccination. 

Dr. Stokely indicated that CDC is looking more closely at the data received from the 13 IIS 

jurisdictions. There is not always a one-to-one correlation between coverage and ordering data. 

While some jurisdictions had lower orders, their coverage did not show as large a decrease as 

some other jurisdictions where the ordering impact was not as large. Further analyses will be 

needed to better understand the relationship between orders and coverage in terms. For 

instance, the amount of stock providers had on hand at the beginning of the pandemic may 

have impacted the amount they needed to order based on fewer children presenting to their 

office. 

Dr. Poehling highlighted that 2 doses work great for those who are immunocompetent who 

begin at 15 years of age. However, those who are immunocompromised always need 3 doses 

of vaccine. In addition, there is a major advantage in starting at a younger age.

Impact of the US HPV Vaccination Program on HPV-Associated Outcomes

Julia Gargano, PhD (CDC/NCIRD) presented an update on the impact of the US HPV

vaccination program on HPV-associated outcomes. Monitoring the impact of the HPV 

vaccination program in the US has been done using a variety of early, intermediate, and late 

outcomes. HPV prevalence has been monitored in several populations using data from the 

National Health and Nutrition Examination Survey (NHANES), women undergoing cervical 

cancer screening, and men who have sex with men (MSM). Anogenital warts have been 

monitored through claims data. Juvenile onset recurrent respiratory papillomatosis (JORRP) has 

been monitored through a network of pediatric otolaryngologists. Cervical precancers have been 

monitored through population-based surveillance and administrative data and state-based data. 

HPV-associated cancers have been monitored through state-based cancer registries.

CDC has collected genital specimens using population-based surveys through the NHANES 

since 2003 for females and since 2013 for males. HPV typing results are linked to demographic

data, limited behavioral data, and self- or parent-reported HPV vaccination history. In the first 4 

years after the vaccination program began, quadrivalent vaccine-type HPV prevalence was 56% 

lower in females 14 through 19 years of age than in the pre-vaccine era.35 By 2015-2018, 

quadrivalent vaccine-type prevalence was 88% lower than the pre-vaccine era among females 

14 through 19 years of age and 81% lower among females 20 through 24 years of age. No

significant decrease was seen in the older age groups and non-vaccine-type prevalence did not 

change significantly. This suggests that the declines in vaccine-type prevalence were not due to 

lower HPV exposure.36

Vaccine impact also was estimated among vaccinated and unvaccinated sexually experienced 

females. In females 14 through 19 years of age, quadrivalent vaccine-type prevalence was 97% 

lower among vaccinated females in 2015-2018 compared to the pre-vaccine era and 87% lower 

among unvaccinated females. In persons 20 through 24 years of age, prevalence was 86% 

lower in the vaccinated group and 65% lower in the unvaccinated group. These data show 

strong direct impact of vaccination, as well as robust evidence of herd protection.37 NHANES 

data also were used to evaluate vaccine impact by race and ethnicity, comparing quadrivalent 

35 Markowitz et al. J Infect Dis 2013 36 Markowitz et al. J Infect Dis 2013; Oliver et al. J Infect Dis 2017; Rosenblum et al. MMWR 2021 37 Rosenblum et al. MMWR 2022
ACIP Meeting Summary June 22-23, 2022

57

vaccine-type prevalence in 2013-2016 to the pre-vaccine era. Among females 14 through 19

years of age, declines in vaccine-type prevalence were significant for non-Hispanic White, nonHispanic Black and Mexican American female.38

The JORRP outcome is caused almost entirely by HPV type 6 and 11 and mainly from vertical 

transmission at the time of delivery. In 2008-2009, declines in US JORRP incidence had begun 

to occur. Those declines continued in every subsequent set of years. The data suggests that the 

number of children with JORRP has declined significantly in the years following HPV vaccine 

introduction for adolescents and young women in the US, and that these declines are most 

likely due to HPV vaccination.39 

Data from population-based surveillance, administrative claims, and cancer registries have been 

used to evaluate vaccine impact on incidence of cervical pre-cancers in the US. Monitoring

impact on pre-cancers is challenging due to changes in cervical cancer screening

recommendations during this time period, including a major change in 2012. Cervical precancers are only detected by screening, so it is preferable to use the number of screened 

women as the denominator in incidence calculations. All approaches have shown decreases

in cervical pre-cancers in young women consistent with vaccine impact.

The HPV-IMPACT project is a 5-site population-based monitoring project that is collecting data 

on pre-cancers and screening. Rates of pre-cancers (CIN2+) among screened women

decreased between 2008-2015 among persons 18 through 20 years of age and 21 through 24

years of age. Rates increased in screening among women in older age groups. Similar

increases in this in this age group have been found in other studies and are thought to be 

attributable to longer screening intervals and/or increased sensitivity of new screening tests.40 

In HPV-IMPACT, typing is performed on tissues from pre-cancerous lesions. In one analysis, 

typing data were used to estimate the number of CIN2+ cases caused by HPV 16 and 18, the 

high-risk types targeted by the quadrivalent vaccine. The estimated numbers of vaccine-type

CIN2+ declined significantly, whereas the estimated number of CIN2+ not caused by HPV 16 

and 18 remained approximately constant, showing that the vaccination program is the most

likely cause of the observed declines in CIN2+ incidence. Finally, trends in invasive cervical 

cancer have been evaluated using data from US Cancer Statistics, which is a database of 

cancer registry data that covers 97.8% of the US population. An analysis by Mix et al, among 

persons 21 through 24 years of age, incidence of invasive squamous cell carcinoma (SCC) of 

the cervix has been in decline for many years due to the cervical cancer screening program. 

This analysis showed that starting in 2012, the slope of the trend became more pronounced. 

These data do not account for changes in cervical cancer screening that started in 2012, so it is 

difficult to know how much HPV vaccination contributed to this trend. Of note, there also was an 

inflection point in persons 15 through 20 years of age in 2011-2012, which is less likely to have 

been influenced by screening.41

In summary, data from impact monitoring projects has shown that prevalence of the

quadrivalent HPV vaccine types has declined markedly among vaccinated and unvaccinated 

young females in the US. The declines in high-risk HPV types 16 and 18 have translated into 

declines in cervical pre-cancer incidence in young women. The declines in HPV type 6 and 11 

have resulted in a reduced incidence of JORP. Early impact on invasive cancer in young women 

38 McClung et al. J Adolesc Health 2019 39 Meites et al, Clin Infect Dis 2021 

40 Gargano et al. Clin Infect Dis 2019; https://www.cdc.gov/ncird/surveillance/hpvimpact/index.html 41 Mix et al, Cancer Epidemiol Biomarks Prev 2020
ACIP Meeting Summary June 22-23, 2022

58

might be occurring. Monitoring will continue to assess the impact of vaccination in females and 

males, and the impact of 9vHPV vaccine. 

1-Dose HPV Vaccination: Overview of Current Evidence

Lauri E. Markowitz, MD (CDC/NCIRD) presented an update on data regarding 1-dose HPV 

vaccination and a review of the recently revised HPV vaccination recommendations of WHO’s 

SAGE, noting that this was not meant to be a comprehensive review or an assessment of the 

data. Instead, it was meant to be an information only update. Currently, there is no active ACIP 

HPV Vaccines WG. This presentation included background information on data that were 

required for initial licensure of HPV vaccines in 2006 and the change to a 2-dose schedule in

2016; a summary of the 1-dose vaccination evidence; and a summary of the SAGE HPV 

vaccination recommendations from the April 2022 meeting.

Efficacy and immunogenicity data that were submitted to FDA for initial licensure of HPV 

vaccines were from trials conducted with a 3-dose schedule, with the second and third doses 

administered 1-2 and 6 months after the first dose. These data were from randomized control 

efficacy trials in women 15 through 26 years of age, The trial endpoints were cervical pre-cancer

lesions.42 Efficacy against vaccine-type endpoints was over 96% in per protocol analyses, which 

included women who were naive to the vaccine types. Seroconversion 1 month after the last 

dose was close to 100%. There also were immunobridging trials in persons 9 through 15 years 

of age as it was not feasible to conduct efficacy studies in this age group and licensure in 

individuals 9 through 15 years of age was based on non-inferior antibody response compared to 

women in the age group of the efficacy trials.

Interest in a 2-dose schedule was stimulated by a post-hoc analysis of a 3-dose RCT in which 

not all individuals completed the schedule. In these analyses, efficacy is against HPV16/18 

infection that was similar after 3, 2, and 1 doses. Following publication of these data,

immunobridging trials were conducted to evaluate 2 doses given an interval of 6 or 12 months in 

persons 9 through 14 years of age compared with 3 doses in women 15 through 23 years of 

age from the efficacy trials. Seroconversion and GMTs were non-inferior in the 2-dose groups 

compared with those in the 3-dose group.43

Looking at some of the results from a 9vHPV 2-dose immunobridging trial, GMTs were noninferior at 1-month post-last dose in girls 9 through 14 years of age who received 2 at 0-6 

months compared with young women 16 through 26 years of age who received 3-doses.44 In 

terms of the immunobridging data from a 4vHPV 2- versus 3-dose immunobridging trial, there 

were 3 groups: 2 doses (0,6 months) in 9–13-year-olds; 3 doses (0,2,6 months) in 9–13-yearolds; and 3 doses (0,2,6 months) in 16–26-year-olds. These data demonstrate titers through 36 

months in which there is non-inferiority of the antibody titers in the 2-dose compared to the 3-

dose group, similar antibody kinetics in all 3 groups, a decline 1 month after the last dose, a 

plateau, and stable antibodies regardless of the number of doses.45 

The 9vHPV manufacturer submitted a supplemental Biologics License Application (sBLA) for a 

2-dose series for individuals 9 through 14 years of age in 2016. FDA approved this application 

in October 2016. ACIP recommended a 2-dose series for persons starting vaccination at 9 

42 Future II Study Group, NEJM 2007; Garland S, et al. NEJM 2007; Paavonen J, et al. Lancet 2007 43 Kreimer AR, Rodriguez AC, Hildesheim A, et al. Proof-of-principle evaluation of the efficacy of fewer than three doses of a 

bivalent HPV16/18 vaccine. J Natl Cancer Inst. 2011;103(19):1444-1451. doi:10.1093/jnci/djr319 44 Iversen O-E, et al. JAMA 2016 and https://www.fda.gov/media/90064/download 45 Adapted from: Dobson SR, et al. JAMA 2013
ACIP Meeting Summary June 22-23, 2022

59

through 14 years of age, while 3 doses are still recommended for persons with

immunocompromising conditions and for persons starting the series at older ages.

Moving to the evidence for 1-dose vaccination, the same studies that stimulated interest

in 2-dose schedules led to interest in 1-dose vaccination. However, immunobridging studies 

were not possible because 1 dose results in lower antibody titers than 2 or 3 doses. The basis 

of protection after vaccination is thought to be neutralizing antibody. However, there is no

minimum antibody threshold for protection. Very low levels of antibody are thought to be 

protective against HPV. Levels lower than those detectable by available assays and efficacy 

trials were felt to be needed to evaluate 1-dose vaccination. There is an efficacy trial being 

conducted by the US National Cancer Institute (NCI). The objectives of this large randomized 

double-blind trial are to: 1) evaluate the non-inferiority of 1 dose compared with 2 doses of 

bivalent and 9-valent vaccines for prevention of 16/18 infections; and 2) evaluate 1 dose 

compared to unvaccinated. Bivalent and 9-valent vaccines are being evaluated separately 

among girls 12 through 16 years of age in Costa Rica who are being followed for up to 5 years. 

The study also includes surveys of unvaccinated women to allow estimates of vaccine efficacy

by comparing persistent infection in these women with the vaccinated trial participants. No 

interim analysis is planned in this ongoing trial and results should be available in 2024.46

Meanwhile, interest in 1 dose vaccination has increased for several reasons. A global HPV 

vaccine supply and demand imbalance was recognized,47 and this limited HPV vaccine

introductions in some countries. While more countries have introduced vaccines,

global vaccination coverage continues to be low.48 In 2020, it was estimated that only 13% of 

girls worldwide were fully vaccinated by age 15. There continued to be challenges implementing 

HPV vaccination programs. Additional studies were initiated to evaluate 1-dose vaccination and 

studies provided the initial data on 1 dose had further follow-up data shown in this table:

In the first 2 trials, Costa Rica and India, participants were not randomized to a 1-dose group but 

there was 1-dose data from post-hoc analyses. The Costa Rica Vaccine Trial (CVT) was the 

trial that originally raised interest in 2 and 1 dose schedules. This study now has data through 

11 years after vaccination from a post-hoc analysis of a RCT. A control group of unvaccinated 

women was recruited after the blinded phase to allow for continued efficacy determination. 

Prevention of prevalent HPV 16/18 infection was similar in all dose groups. Antibody also was 

measured through 11 years of follow-up in this study. While the antibody titers were lower in the 

46 Porras, et al. Vaccine 2022 47 WHO. Global Market Study, HPV. who-hpv-vaccine-global-market-study-april-2022.pdf 48 Bruni L, et al. Preventive Medicine 2019
ACIP Meeting Summary June 22-23, 2022

60

1-dose group than the 2 or 3 dose groups, titers were relatively stable in all dose groups to 11 

years after vaccination and at least 10-fold higher than in the unvaccinated group.49

The India IARC trial was designed as a cluster randomized trial to compare 2 versus 3 doses of 

4vHPV vaccine and was initiated in 2009. Less than a year after vaccination, HPV vaccinations 

were stopped by the Indian government due to issues unrelated to this trial. However, much of 

the enrollment randomization and initial vaccination had occurred. Although not all participants 

could complete the schedule to which they were randomized, the study has been analyzed as 

an observational cohort with 4r different vaccination schedules, including a 1-dose group.50

Participants were followed yearly, and data are now available through 10 years after 

vaccination. Cervical specimens were collected 18 months after marriage or 6 months after first 

childbirth to assess HPV infection. Unvaccinated women were age-matched to the married 

vaccinated participants and recruited as controls. VE against persistent 16/18 infections was

analyzed adjusting for the imbalance and distribution of potential confounders, and efficacy

against persistent 16/18 infection was similar in all dose groups.51

Now moving to the more recently conducted trials in which participants were randomized to a 1-

dose group, the KENya Single-dose HPV-vaccine Efficacy (KEN SHE) Study is a randomized,

Double-blind controlled trial conducted in Kenya published last year. Young women aged 15

through 20 years of age were randomized to 1 dose of 9vHPV, 1 dose of 2vHPV, or 1 dose of 

meningococcal vaccine (MCV). A total of 1458 women were evaluated for efficacy at month 18

in the modified intent-to-treat cohort who comprise participants who tested HPV antibodynegative at enrollment and DNA-negative at enrollment in month 3. There were 38 incident 

persistent infections detected, one each among participants in the 2vHPV and 9vHPV groups

and 36 in the MVC. VE was 97.5% for both HPV vaccines. In the efficacy data against all 7 

oncogenic types targeted by the 9vHPV vaccine, there were 29 infections in the control group 

and 4 in the 9vHPV group for efficacy of 88.9%.52

The Dose Reduction Immunobridging & Safety Study (DoRIS) in Tanzania is a randomized trial 

of 1, 2, and 3 dose of 2vHPV or 9vHPV vaccine. The study included 930 Tanzanian girls aged 9 

through 14 years. The objectives were to demonstrate non-inferiority of HPV 16/18 antibody

after 1 dose compared with 2 or 3 doses of the same vaccine at Month 24 and to demonstrate 

non-inferiority of HPV 16/18 GMCs comparing 1 dose in this study with 1 dose in studies that 

evaluated efficacy. For HPV-16, non-inferiority criteria were met for 1 dose compared to 2 or 3 

doses for both vaccines. For HPV-18 seropositivity was greater than 97.8% in all dose groups, 

but non-inferiority criteria were not met for 1 compared with 2 or 3 doses. GMCs declined for 1 

and 2 doses after a peak of 1 month. The levels plateaued and were similar at all time points.

The GMCs for 1 dose were lower than for 2 or 3 doses; however, there was a stable plateau as 

has been seen in other HPV vaccine studies. This study also conducted a variety of other

evaluations. One analysis looked at avidity, which is a measure of the strength of binding of

antibody to antigen. This was similar regardless of number of doses received or the vaccine. 

Immunobridging analyses showed that seropositivity and GMCs were non-inferior in the 1-dose 

groups in this study compared with those in the 1 dose groups in the trials where efficacy was 

observed.53

49 Kreimer AR, et al. J Natl Cancer Inst 2020 

50 Sankaranarayanan R, et al. Lancet Oncol 2016 51 Basu P, et al. Lancet Oncology 2021, with updated data 52 Barnabas R, et al. DOI 10.21203/rs.3.rs-1090565/v1; NEJM Evidence 2022

53 Watson-Jones D, et al. http://dx.doi.org/10.2139/ssrn.4055429 
ACIP Meeting Summary June 22-23, 2022

61

The Thailand impact study is an observational study of 1 dose and 2 doses of 2vHPV vaccine 

given to Grade 8 girls <15 years of age in 2 similar provinces in Thailand. The primary 

objectives are to demonstrate HPV VE of 1 dose and 2 doses at Years 2 and 4 postvaccination. Effectiveness was measured by comparing vaccine-type prevalence in Years 2 and 

4 versus unvaccinated same grade girls in a baseline survey. There also will be an evaluation to 

determine if the HPV VE of 1 dose is non-inferior to 2 doses, which will be done at Year 4. The 

results for Year two are available and found that crude VE against HPV 16/18 was 83.3% in the 

1 dose province and 93.6% in the 2-dose province. Of note, there were some differences

between the provinces, with more girls in the 1-dose province being sexually active at baseline. 

In both provinces, there were differences in risk behavior in the Year 2 survey compared with 

the baseline survey. There were several methods used to adjust for exposure risks, none of 

which these resulted in important changes in the effectiveness estimates.

Extensive modeling has been conducted to evaluate the potential impact of 1 dose vaccination

under assumptions that efficacy and duration are less than for 2 doses, although most

of the clinical studies have not shown this. Dr. Markowitz shared some of the modeling findings.

Compared to no vaccination, 1-dose vaccination yields substantial health benefits and is a good 

value for the money even if the efficacy is lower (80%-85% vs 100%) and duration of protection

is shorter (10-20 years vs lifelong) than with 2 doses. The impact and cost-effectiveness of 

adding a second dose is driven by duration of protection and possibly the ability to achieve 

higher coverage or expand catch-up with 1 dose versus 2 or 3 doses. The projected impact and 

cost-effectiveness of 1 versus 2 doses using a comparative modeling approach has been

conducted by 3 modeling groups with extensive experience with HPV vaccine modeling.54

WHO’s SAGE reviewed these and other data in April 2022 and made revised recommendations,

which were published on June 17, 2022.55 This report states that:

“On the basis of recent data on efficacy and effectiveness, SAGE endorsed the 

optimization of the HPV vaccine schedules. For 9-14-year-olds, national immunization 

programmes can use either a single-dose or a 2-dose vaccination schedule with an 

interval between doses at least 6 months.” 

“This off-label option for routine and multi-age cohort (MAC) catch-up vaccination is 

recommended from a public health perspective, on the basis of providing comparable 

levels of individual protection while being more cost-effective and efficient (fewer doses 

per cancer case prevented), providing more programme flexibility, and enabling the 

expansion of the MACs targeted.”

54 Jit M, et al. Fewer than three doses of HPV vaccine. Lancet Oncol 2015; Burger E, et al. Health and economic benefits of singledose HPV vaccination in a GAVI-eligible country. Vaccine 2018; Prem K, et al. Global impact and cost-effectiveness of one-dose 

versus two-dose human papillomavirus vaccination schedules: a comparative modelling analysis. medRxiv. 

2021:2021.02.08.21251186. https://terrance.who.int/mediacentre/data/sage/SAGE_Slidedeck_Apr2022.pdf 55 Meeting of the Strategic Advisory Group of Experts on Immunization, April 2022: conclusions and recommendations 

https://apps.who.int/iris/bitstream/handle/10665/356579/WER9724-eng-fre.pdf
ACIP Meeting Summary June 22-23, 2022

62

This table shows 2017 WHO recommendations, which are still considered the current

recommendations until publication of the revised position statement and the 2022 Sage 

recommendations:

The primary group recommended for that vaccination programs is unchanged (e.g., girls aged 

9-14 years). Either a 1-dose or 2-dose schedule can be used for individuals 9-14 or 15-20 years

of age. SAGE recommended that a 2-dose schedule can be used for persons ≥21 years of age. 

At least 2 doses, but ideally 3 doses if feasible, are recommended for persons who are 

immunocompromised. The recommendations for the number of doses for boys and men 

remained the same.

There are at least 3 additional studies shown in the table below that are anticipated to provide 

additional data on 1-dose HPV vaccination:

In summary, HPV vaccines were first studied and licensed in a 3-dose schedule in persons

aged 9 through 26 years and later in a 2-dose schedule in persons aged 9 through 14 years. 

There are now data on 1-dose vaccination, including efficacy data from an RCT with 18-month 

follow-up. Long-term follows from other studies suggest good duration of protection with 1 dose.

SAGE recommends 1 or 2 doses in the primary target age groups. WHO will consider and

revise recommendations later this year. There is no regulatory approval for 1-dose vaccination

in any age group or for 2-dose vaccination in any age group older than 14 years of age. The 

HPV team in the Division of Viral Diseases of NCIRD will continue to provide updates on these 

data and will discuss them with ACIP as requested and will collaborate with and provide

assistance to international partners.
ACIP Meeting Summary June 22-23, 2022

63

Discussion Summary

Referring to Slide 15, Dr. Daley said his crude understanding of antibody titers was that they

typically would decline over time at some rate. In the context of all the other vaccine work that 

the ACIP does, including COVID-19 vaccination, he asked whether something is different about 

the HPV vaccine being VLPs or if there was something else that explained why there is not a 

declining antibody titer over time. 

Dr. Markowitz indicated that there has been a lot of discussion about this. She summarized

some data from a talk that Professor Stanley from Cambridge recently gave. The feeling right 

now is that it is that the VLP size and geometry make this highly efficacious and immunogenic. 

The size is optimal for entry into the lymphatics and transport to the B-cell follicles. This particle 

size is readily taken up by dendritic cells. There has been a lot of focus on the VLP because it is 

a multivalent protein antigen with 360 copies of the L1 proteins that are assembled in a very 

dense, repetitive array, which is felt to be very important for the immunogenicity of this vaccine.

It is fascinating and if ACIP is interested, a session could be arranged for discussion about the 

current thinking regarding why this vaccine is so highly immunogenic and effective.

Dr. Daley asked whether the size of the VLPs is related to the size of the virus in terms of the 

outer membrane of an HPV virus, or if it is independent of that and is just a really efficient way 

to present antigen to the immune system that does not relate to the size of the virus it is trying to 

mimic. 

Dr. Markowitz said she thinks it is related to that because the VLP is like an authentic virus and

looks like the HPV virus.

Miss Bahta recalled the presentations in 2006 and beyond and thinking long-term outcomes 

were so far away, yet they are now hearing about long-term outcomes that are incredibly 

encouraging. However, many adolescents are still missing the opportunity for protection.

Related to Dr. Gargano’s presentation, on Slide 8 there was a 74% lower prevalence in nonHispanic Black compared to 86% in non-Hispanic White females 14–19 years of age from 

2013–2016 compared to the pre-vaccine era. She wondered why that not lower if the 

vaccination rates were higher, and whether perhaps there are some HPV types that are not 

being covered by the vaccine. 

Dr. Gargano said she did not think it was related to the types, because the McClung study was

looking at the vaccine targeted types and the prevalence of those types. While she did not have 

the data to give a definitive answer on why the percent decrease was somewhat lower in that 

particular group, it may have to do with a discrepancy in the age of vaccination and age at onset 

of sexual activity. Those are not captured in the data.

Dr. Sanchez stressed how remarkably effective this vaccine has been, particularly in terms of 

the decreases in cases of JORRP. He was somewhat hesitant in terms of recommending a 1-

dose schedule given the progress that has been made and even though many people are still 

unvaccinated. He would want more long-term follow-up information before making a 

recommendation about giving 1 or 2 doses. In addition, he thought they should be firmer about 

recommending 1 dose or 2 doses. He did not like saying either one could be done.

Dr. Poehling emphasized how wonderful it was to see the impact that the HPV vaccine has had

throughout the world. She asked whether any manufacturers would be submitting a 1-dose

request to the FDA. 
ACIP Meeting Summary June 22-23, 2022

64

Dr. Kimberlin (AAP Redbook) asked whether there are any other vaccine-preventable diseases 

for which VLP vaccines are in development.

Dr. Fink (FDA) emphasized that the FDA is not allowed to disclose non-public information

about vaccine developers who may have products under development or under the

Investigational New Drug (IND) program. However, there are examples of VLP platform 

vaccines that have been in the public domain, including a COVID-19 vaccine manufactured by 

Medicago, a Canadian manufacturer that uses a VLP platform. 

Dr. Long observed that pharmaceuticals have focused on immediate antibody responses at 1 or 

2 months and want to present that, and that has been thought of as the “Holy Grail.” In fact, that 

is probably not even close. It is a cellular response and is about how the first exposure alters the

immune response and makes memory cells that result in continuous stimulation of antibody

responses. In this case, it looked as if the second and the third dose achieved spurious levels

that did not really matter. The graph showing what happened after 1 dose that did not decrease 

as abruptly and suggested that overstimulating when it is not needed can get an antibody

response for a short period of time and could be good for the short-run, but says nothing about 

the long-run. The short-term responses for the Coronavirus vaccines seems to be spurious in

that they are very high, but they go away very fast. Here, 2 and 2 doses are spurious because 

they are very high, but they do not mean anything. She wished they could get to more

sophisticated requirements for antibody tests further down the line, not just the one after the last 

dose of vaccine, in order to have more sophisticated ways to look at immunization responses

that are not dependent on just antibodies. She asked whether the FDA could say whether they 

were thinking about any new paradigms of how to assess vaccine responses, and what the

optimal way would be to determine an adequate versus an inadequate response.

Doran Fink (FDA) responded that clearly, at least with certain vaccines, antibodies are not the 

whole story. To explain the mechanism of protection, antibodies historically have been the

component of the immune response that is most amenable to evaluation including for bridging 

analyses that require the use of validated assays and high throughput assays to assess large 

numbers of samples. Clearly, there is interest in exploring how other components of the immune 

response, such as cell-mediated immunity (CMI), can be leveraged to inform regulatory 

decisions and understanding of VE. At this point, they are not able to use CMI response assays

in the same way that they have come to rely on antibody-based assays. To the extent that the 

field can move forward and develop the assays and the science, FDA is happy to be involved in 

the discussion.

PUBLIC COMMENTS JUNE 22, 2022

Overview 

The floor was opened for public comment on June 22, 2022 at 3:00 PM ET. Given that many 

more individuals registered to make oral public comments than could be accommodated during 

this meeting, selection was made randomly via a lottery. Dr. Lee provided a gentle reminder that 

the ACIP appreciates diverse viewpoints that are respectful in nature and issue-focused rather 

than comments directed at individuals. The comments made during the meeting are included in 

this document. Members of the public also were invited to submit written public comments to 

ACIP through the Federal eRulemaking Portal under Docket No. CDC-2022-0062. Visit 

http://www.regulations.gov for access to the docket or to submit comments or read background 

documents and comments received.
ACIP Meeting Summary June 22-23, 2022

65

Public Comments

Karyne Jones

President and Chief Executive Officer

National Caucus and Center on Black Aging

My name is Karyne Jones. I am the President and Chief Executive Officer (CEO) of the National 

Caucus and Center on Black Aging (NCBA). We appreciate this committee’s ongoing

commitment to ensuring access to a wide variety of vaccines, especially in the wake of the 

ongoing COVID-19 pandemic. However, I must use my time today to express my 

disappointment that this committee chose once again not to include clarification of the needed 

use of new adult vaccines for pneumonia. While these vaccines were approved last June by the 

FDA, the guidelines which were released by the CDC in January of this year did not provide

clear guidance on whether older adults who had already received the pneumonia vaccine were 

eligible for the new and improved vaccines. This leaves two-thirds of Americans over the age of 

65 uncertain of whether they too can have access to these new protections. As we continue to 

face respiratory threats with COVID-19 and the upcoming flu and pneumonia season this fall,

why wouldn’t we also take up the important step to ensure such a vulnerable population has 

access to the best protections available? While we certainly support the focus on ensuring that

the newest vaccines are available for children, we can’t help but wonder why this can’t be done 

at the same time as offering clarification for older adults as well. I have also previously shared 

comments with this committee on the importance of lowering the age-based recommendation 

for adult vaccines to those aged 50 and over. In ACIP’s 2021 meeting, data was presented

showing that this change would increase vaccinations among those living with risk of serious 

illness and therefore would likely to help address disparities and the uptake in these vaccines 

among minority populations, as well as provide cost-savings for the system. This was incredibly 

encouraging and yet, we’ve not heard any further discussion on this proposal. Given that black 

and brown communities often experience the onset of chronic illnesses earlier than 65 due to 

environmental factors beyond their control and the effect of lifetime of inequitable care,

providing protection for these individuals earlier in life will not only offer earlier intervention for 

those at risk, but provide critical protections before immune system efficacy wanes as part of 

normal aging. We strongly encourage this committee to review any remaining data needed and 

provide clear guidance on the use of the pneumonia vaccines to ensure they are available to a 

full population of vulnerable Americans before the upcoming flu and pneumonia season. We

also welcome the opportunity to continue discussions around the benefits of lowering the agebased recommendations to help close the disparity gaps and reduce the number of preventable 

deaths in this country. Thank you very much.

Kevin Tuttle

Public Relations Director

Schara Family

Hi. I’m Kevin Tuttle, the Public Relations Director for the Schara Family. I’ll get to their story in a 

moment. No matter what I say to the ACIP board today, they’ll ignore it like they’ve ignored

grieving parents over vaccine injury for decades. We know this board has no conscience, but 

I’m not trying to reach them. I’m trying to reach those of you who know that something is up but 

can’t figure it out. It’s called genocide. Why have myocarditis, blood clots, Bell’s palsy, infertility, 

and Gavin Newsom’s favorite, GBS, skyrocketed since jabs got into arms warp speed? What 

about death? All-cause mortality was not higher in 2020 than 2019. Isn’t that odd for such a 

deadly pandemic? But it’s certainly higher since the COVID jabs came out. Must be those darn 
ACIP Meeting Summary June 22-23, 2022

66

anti-vaxxers. Why are the jabbed keeling over? Medical professionals are baffled, but they

created a term, Sudden Adult Death Syndrome (SADS). This is history repeating itself. The ‘86 

National Childhood Vaccine Injury Act (NCVIA) created a system that denies the link between

vaccines and harm. When vaccines and doses increased after that act, babies started dying and 

they called it sudden infant death syndrome (SIDS). See how that works? “Died suddenly” is all 

the rage these days amongst the jabbed, followed closely by “half my face doesn’t work.” This 

criminal board won’t address it and put an end to these toxic jabs because that would mean

they’re culpable for the deaths occurring. The AAP just announced updated infant sleep

recommendations right after the jab was approved. Is that odd to anyone? This means they will 

blame parents for their child’s death rather than look at the jab having caused the death. SIDS is 

about to explode, and this board needs to be held accountable. This is genocide led by medical 

institutions and government. They did the same thing in Nazi Germany. Doctors worked for the 

regime. They would order dangerous medicines be given to the disabled, the useless feeders,

and nurses would administer the deadly drugs. It was a government-planned, governmentsupported mass extermination of people. They could not have done it then without the support 

of diabolical physicians, scientists, nurses and media just like now. That’s why they tried to 

silence non-conformists like Drs. Nicola, Corrie, Paul, Thomas—something Josef Goebbels

would have done in 1939. What was good for the state was more important than what was good 

for the individual, just like now. Nothing has changed despite the Nuremberg Code. Take Grace 

Schara for example. Within a 29-minute window, she was given Precedex, Lorazepam, and 

morphine without reason. She was 19, but Grace had Down’s Syndrome, which was apparently 

enough for St. Elizabeth’s Ascension Hospital in Appleton, Wisconsin to designate her a useless 

feeder and kill her off through health care. Did Dr. Gavin Shokar know a max dose of Precedex 

could take Grace out? Is that why he submitted a DNR order on her without family consent eight 

minutes after the sedative was given? This is the type of care one should now expect in

hospitals. Avoid them at all costs. Let history be your guide. “I was just doing my job,” didn’t fly

in the Nuremberg trial. It won’t fly for this board or those injecting people with the death shot at 

the next trial. Stop the genocide. Say “no” to all jabs, people. Thank you.

Milena Berhane, MPH

Health Policy Associated

National Consumers League

Thank you, Dr. Lee. My name is Milena Berhane and today I’m representing the National 

Consumers League (NCL). Since NCL’s founding in 1899 by social reformer Florence Kelley, 

we have advocated for the critical role that immunizations play in the preservation and

improvement of public health. We extend our gratitude to this committee for the opportunity

to present public comments. According to the National Foundation for Infectious Diseases,

pneumococcal disease is a leading cause of serious illness throughout the world. In the US, 

nearly 50,000 people die each year from pneumonia, and the death rate is even higher in those 

ages 65 years of age and older. Vaccination is a critical public health measure for preventing 

disease, hospitalizations, and deaths, so it is critical that access to the pneumococcal vaccine is 

expanded. We are concerned about the lack of clarity surrounding the current ACIP

recommendations regarding the pneumococcal vaccine for adults ages 65 years of age and 

older. It is critical that the recommendations for this age group is clear so that patients and

providers are better able to understand who should receive which vaccine and when. The

pneumococcal vaccine will continue to be a safe and effective measure in protecting Americans 

from disease, and it is imperative that older adults are able to receive them. Having clear

recommendations for adults 65 years of age and older is also critical in addressing health equity 

issues, especially among older Black and Latinx populations that already face issues and lack

access to health care. Pneumococcal vaccine uptake needs to increase in these populations, so 
ACIP Meeting Summary June 22-23, 2022

67

that the currently existing health disparities are not further exacerbated. Therefore, in order to 

promote health equity among all older adults and increase vaccination rates, it is critical that 

clear recommendations are provided for this age group. The National Consumers League 

recognizes the extreme importance of immunizations in protecting the health and safety of all 

Americans, and we’ll continue with efforts to increase vaccine confidence and uptake across 

lifespan. We look forward to the upcoming recommendations by this committee regarding the

pneumococcal vaccine for older adults. Thank you.

Vangelis Russos 

Individual

There is no long-term safety data for COVID-19 vaccinations in young children, so vaccinating 

them is an experiment, and this experiment is not looking good. We already know that COVIDvaccinated children 12 to 17 years old have a 5-fold increase in myocarditis. Those are not my

words. Those are the words of Dr. Peter Marks from the FDA. Currently, about 1.3 million

injuries have been reported to VAERS for all age groups. This includes anaphylactic shock, 

allergic reactions, blood clotting and other bleeding disorders, myocarditis, pericarditis, stroke, 

heart attacks, tinnitus, death, and more. Some children will die, and others will be permanently 

injured from these shots. Why should children be forced to take this risk when they have a 

99.995% recovery rate, which means that almost zero kids have died from COVID-19? In

February 2022, the CDC said over 75% of children already have partial or full immunity to

COVID. COVID vaccines do not stop transmission or infection. There is no statistically valid 

evidence that they prevent severe disease or death in children. The current COVID vaccines 

were formulated based on the original Wuhan strain, and were not tested for benefit against 

current variants in clinical trials. These vaccines are not science-based medicine. They are

neither safe or effective. In fact, Pfizer’s clinical trials for 2- to 4-year-olds failed to meet FDA 

requirements to show 50% efficacy. The vaccine failed the FDA’s established criteria in its 

clinical trials. This is clearly not about science and facts, so what is it about? If we don’t stick to 

the facts in science, this will lead the public into thinking something more nefarious is going on.

Is it? COVID is not a public health threat. You know what the real health threat is? People in the 

position to protect the public that do not, so I want to ask if any of you have the courage

to be real scientists. You actually have a chance to be true heroes. The facts clearly show that

this vaccine will do more damage than it will prevent, so why are you doing it? So, you actually 

have a chance to be true heroes. So, now is the time to be remembered in history as a hero, or 

you could be remembered as a coward. The choice is yours. Thank you.

Itzia Irineo

Individual

Hi. Good afternoon. Thank you. My comment is going to be very quick. Why are we giving this 

injection to especially kids that are 5 years and under, when clearly their immune system and 

brains isn’t fully developed? That’s my question. And number two is most vaccines takes up to 

10 years to get approved by the FDA. And why are we giving this injection still when it’s under 

EUA? And that’s all.
ACIP Meeting Summary June 22-23, 2022

68

Robert Blancato

Executive Director

National Association of Nutrition and Aging Services Program

Members of the committee, my name is Bob Blancato. I’m Executive Director of the National 

Association of Nutrition and Aging Services Program (NANASP). NANASP has appreciated the 

opportunity to submit an oral comment. As I have done in my prior testimony, I start by

commending ACIP for your hard and dedicated work throughout this pandemic. I join my

colleague Karyne Jones and offer my comment to specifically register our deep disappointment 

in the failure of this committee to include any discussion or action on clarifying current CDC 

guidance on older adults having access to new and improved pneumococcal vaccines on the 

agenda, including all those over 50. NANASP was joined by several other national aging 

patients and healthcare organizations in petitioning ACIP to include this discussion on the June 

agenda. In fact, we also specifically wrote to four ACIP members, all of whom expressed some 

sympathy with our request. At the heart of the matter is that under the current guidance, only 

those older adults who have never received a pneumococcal vaccine are eligible to receive a 

new vaccine. The rationale as provided in an email from Melissa Wharton was that, “The

greatest benefit from the new pneumococcal vaccines now will be in adults who have not yet 

received pneumococcal vaccines.” Overlooked by this rationale is the 67% of older adults who 

have already received a pneumococcal vaccine who have no access to the new vaccine. Also 

overlooked is how long it may have been since some of these older adults received their first 

vaccine. And given that we know the strength of the immune system wanes as individuals age, 

ensuring access to improved versions of the vaccine which protect against more strains of

disease is a critical and greater level of protection that we should not be denying older

Americans. We should never forget that older adults had a disproportionately higher death

rate from pneumococcal pneumonia than other groups. Their vulnerability is genuine. Our main 

point is that CDC should consider the benefit that access to these new vaccines for all older

adults would have. Our nation’s health care system can “walk and chew gum at the same time.” 

It is possible to both vaccinate older adults who have already received vaccines and those who 

have not. Older adults who were previously vaccinated should not be penalized for having done 

the right thing already. We implore members of ACIP to clarify this guidance by recommending 

these new and improved pneumococcal vaccines be made available to all older adults 

previously vaccinated or not. That is the most equitable approach. We thank the committee for 

considering our comments.
ACIP Meeting Summary June 22-23, 2022

69

THURSDAY: JUNE 23, 2022

WELCOME & INTRODUCTIONS

Call to Order/Roll Call

Dr. Grace Lee (ACIP Chair) called to order and presided over the second day of the June 22-

23, 2022 ACIP meeting. She conducted a roll call, 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. The following COIs were declared:

 Dr. Chen indicated that his employing institution, the University of Maryland, received a 

grant from Emergent BioSolutions that supported work he conducted to develop a shigella 

vaccine. This relationship with Emergent BioSolutions ended about 6 months ago in 

December 2021. Given that vaccines in development by Emergent BioSolutions may be 

discussed during the day, although there would not be any related votes and it did not seem 

to be an actual COI, he mentioned it as a potential perceived conflict.

AGENCY UPDATES

Centers for Disease Control and Prevention

Dr. Romero began by saying how honored he was to be back with ACIP as the new Director of 

the CDC’s National Center for Immunizations and Respiratory Diseases (NCIRD). He reported 

that in early May, Dr. Georgina Peacock accepted the permanent position as Director of the 

NCIRD Immunization Services Division (ISD). Dr. Peacock joined the team almost 10 months 

ago serving as the Acting ISD Director. She brought valuable and relevant experience, most 

recently from her leadership roles in the COVID-19 Response Vaccine Task Force, the Georgia 

Department of Public Health (DPH), and the CDC’s Division of Human Development and 

Disability (DHDD) within the National Center for Birth Defects and Developmental Disorders

(NCBDDD). NCIRD is thrilled to have Dr. Peacock as part of its leadership team. She will apply 

her wide-ranging expertise and experience in implementing population health programs to face 

challenges and reimagining the pillars of preventive healthcare and pandemic response, the 

domestic immunization portfolio, and emergency capability. 

Dr. Romero thanked everyone who worked on the important issues and votes the previous day.

Regularly scheduled ACIP meetings are essential to the work CDC must do to revitalize and 

prioritize routine immunization for all ages. Despite signs that the pandemic has clearly 

disrupted childhood immunizations, routine vaccine coverage remains high, and the agency 

looks forward to working with the broader public health community to recover ground that was 

lost during the pandemic. This work includes gearing up for the upcoming influenza season. The 

US is well-positioned with vaccines that can protect people from influenza’s most serious 

consequences. The preferential recommendation vote will continue to help make certain that 

older adults receive the influenza vaccines that best protect them. It also may assist in efforts to 

address health disparities by making these vaccines more available to racial and ethnic minority 

groups. CDC looks forward to working with all of its partners on the implementation challenges 

and considerations in removing these disparities as quickly as possible.
ACIP Meeting Summary June 22-23, 2022

70

In terms of outbreaks, meningococcal disease is a major issue in Florida at this time. There is 

an ongoing deadly meningococcal disease outbreak in Florida spreading primarily among gay 

and bisexual men. It is one of the worst outbreaks of meningococcal disease among gay and

bisexual people in the history of the US. At least 24 cases and 6 deaths have been reported 

among gay and bisexual men. CDC currently is recommending that gay, bisexual, and other

men who have sex with men (MSM) get a MenACWY vaccine if they live in Florida or talk with 

their healthcare provider about getting vaccinated if they are traveling to Florida. CDC also is 

emphasizing the importance of routine MenACWY vaccination for individuals with Human 

Immunodeficiency Virus (HIV). With regard to monkeypox, the CDC continues to track multiple

cases of monkeypox that have been reported in several countries that do not normally report

monkeypox—including the US. The agency also is closely watching the World Health

Organization (WHO) International Health Regulation (IHR) Emergency Committee meeting 

through the day to determine whether the multi-country monkeypox outbreak constitutes a 

public health emergency of international concern (PHEIC). The CDC will provide frequent

updates as more is learned. 

Centers for Medicare and Medicaid

Ms. Hance reported that during the February ACIP meeting, she mentioned that the Center for 

Medicare and Medicaid Services (CMS) has established a policy of covering stand-alone 

vaccine counseling. Guidance was issued on that on May 12, 2022 and CMS announced the 

new stand-alone vaccine counseling program on June 8, 2022. CMS continues to provide 

updated information around COVID-19 vaccines after decisions are made by the FDA and CDC. 

They issued a listserv announcement on June 22, 2022 regarding a decision over the weekend 

to expand the vaccines to the youngest children. They will continue to update toolkits, websites, 

and all other materials that CMS releases whenever those decisions are made to keep them 

current.

 

Food and Drug Administration 

Dr. Fink presented the Food and Drug Administration (FDA) update, reporting that on Tuesday, 

June 28, 2022, the FDA will convene its Vaccines and Related Biological Products Advisory

Committee (VRBPAC) to discuss potential updates to the strain composition of COVID-19

vaccines for use in the US. Available data continue to support that current vaccines, which are 

based on the ancestral Wuhan strain of SARS-CoV-2, continue to offer protection against more 

severe COVID-19, especially when booster doses are administered as part of the vaccination

regimen. However, circulating variants of SARS-CoV-2 are becoming increasingly antigenically

distinct from the vaccine. There is an opportunity ahead of the fall and winter months when

there is expected to be the potential for additional surges and the potential for other emerging 

variants, to improve the protection afforded by vaccines by bringing their antigenic components

more in line with the variants that are circulating and may emerge in the future.

In terms of the 2 ACIP votes the previous day on the recently approved PriorixTM MMR vaccine

and VAXNEUVANCETM 15-valent pneumococcal vaccine was approved for use in pediatric

populations, these approvals were the result of a tremendous amount of work by the FDA 

review staff—especially considering the complexity of the applications that both included 

multiple studies involving many thousands of study participants and the level of review 

resources that the FDA currently has at its disposal given other competing priorities. The fact 

that the FDA was able to get these approvals completed within the statutory timelines speaks to 

the tremendous dedication and sacrifice that FDA’s review staff continue to make during these 

times.
ACIP Meeting Summary June 22-23, 2022

71

Health Resources and Services Administration

Dr. Rubin presented the update for the Health Resources and Services Administration (HRSA) 

Division of Injury Compensation Program (DICP). The National Vaccine Injury Compensation 

Program (VICP) continues to process an increased number of claims. In fiscal year 2022, as of 

June 1, 2022, petitioners filed 601 claims with the VICP. Nearly $120 million was awarded to

petitioners, including their attorneys’ fees and costs. As of June 6, 2022, the VICP had a

backlog of 1,439 claims alleging vaccine injury awaiting review. As of June 1, 2022, the

Countermeasures Injury Compensation Program (CICP) had received 8,439 claims alleging 

injuries or deaths from COVID-19 countermeasures. This included 5,449 claims alleging injuries 

from COVID-19 vaccines. Of these, 31 claims have been denied compensation and 1 claim has

been determined medically eligible for compensation. However, compensation has not been

awarded yet and is pending a review of eligible expenses. More information can be found on the 

VICP and the CICP websites. 

Indian Health Service

Dr. Clark presented an update on behalf of the Indian Health Service (IHS), reporting that IHS 

continues to confront the SARS-CoV-2 pandemic and its impact on population health and

routine immunization efforts. Since September 2020, the IHS COVID Vaccine Task Force has 

coordinated the distribution and administration of COVID-19 vaccines agency-wide, including at 

federal direct care facilities, tribal health programs, and urban Indian organizations that receive 

vaccines through the IHS jurisdiction. Collaborating with its federal, tribal, and urban Indian 

organization partners, the IHS has prioritized equitable access to COVID-19 vaccines through 

Indian country. To date, participating federal, tribal, and urban facilities within the IHS 

jurisdiction have administered over 2.2 million COVID-19 vaccines. According to current CDC 

tracker data, among the estimated 2.1 million people served at IHS facilities, including American 

Indian and Alaska Native (AI/AN) individuals, healthcare workers, and community members, 

approximately 42% are fully vaccinated and 32% of those who are fully vaccinated have

received a booster dose as IHS continues to mitigate the impact of serious COVID-19 illness in 

Indian Country. Following recent regulatory actions by the FDA and CDC earlier in the week, the 

IHS rapidly communicated information regarding COVID-19 vaccines for children under 5 years 

of age. They anticipate that a majority of children in this age group will be vaccinated in their

IHS medical homes. Federal, tribal, and urban facilities are now actively engaged in 

implementation. Across IHS’s 3 surveillance systems, IHS COVID-19 vaccine safety monitoring 

has demonstrated a reassuring safety profile to date that is consistent with other national 

vaccine safety surveillance systems. Meanwhile, the IHS routinely collaborates with the CDC 

and engages with tribal leaders to support vaccine confidence among the AI/AN service

population. Lastly, the IHS immunization program has leveraged COVID-19 vaccination

strategies to efficiently implement new and expanded ACIP eligibility recommendations within its

service population for adult pneumococcal, zoster, and hepatitis B vaccines. The immunization 

program developed a resource and clinical guidance document and conducted training to

support implementing pneumococcal and zoster recommendations in the field. The IHS looks 

forward to continued collaboration with its tribal, urban, and federal partners to ensure access to 

safe and effective vaccines across the age spectrum for AI/AN populations served by the IHS. 
ACIP Meeting Summary June 22-23, 2022

72

National Institutes of Health 

Dr. Beigel presented the National Institutes of Health (NIH) update, reporting that the NIH

continues to invest in multiple COVID-19 vaccine efforts. In March 2022, the National Institute of 

Allergy and Infectious Diseases (NIAID) began a study using both prototype and variant

vaccines to try to inform how best to cover the COVID-19 antigenic landscape in terms of known 

variants and variants that may emerge in the ensuing months. The study examined 5 to 6 

strategies for 3 vaccine manufacturers (e.g., Moderna, Pfizer, Sanofi) using the covariant

vaccines. The goal is to understand the immediate need and how to modify the immune

response in the future. This study should contribute a lot of interesting data. The NIH continues 

to evaluate work on allergic reactions to COVID-19 vaccines. A new study was recently started

at the NIH Clinical Center in Bethesda to evaluate people who have had allergic reactions from 

COVID-19 mRNA vaccines. This very detailed analysis will try to understand the etiology of

some of these reactions. The NIH has published an interesting article looking at maternal 

vaccinations that details immunology regarding transplacental antibodies and antibodies in the 

newborn in terms of the kinetics.

In terms of non-COVID-19 work, the NIH launched a clinical trial with 3 mRNA HIV vaccines 

which like the mRNA platform that has been incredibly valuable for COVID-19, have resulted in 

robust immune responses in HIV. The hope is that this will enable diseases such as HIV to be 

treated with vaccines. The NIH is very excited about this vaccine that is being studied through 

the HIV Vaccine Trials Network (HVTN). There is a new vaccine for the Eastern Equine, 

Western Equine, and Venezuelan encephalitis viruses. This is a trivalent virus-like particle (VLP) 

vaccine that has been developed at the NIH Vaccine Research Center (VRC) that has been 

shown to be safe and has generated robust immune responses. Given that these viruses cause 

diseases with often fatal encephalitis, having an effective vaccine is critical. Lastly, the NIH 

launched a new clinical trial for Epstein-Barr vaccine. Epstein-Barr causes infectious 

mononucleosis and also is associated with certain cancers and autoimmune diseases. This 

vaccine uses novel ferritin nanoparticles for vaccine development. There has been limited work 

on Epstein-Barr vaccines in over a decade. The details for all this work will be provided in 

summaries to the ACIP. 

Office of Infectious Disease and HIV/AIDS Policy 

Dr. Kim presented the Office of Infectious Disease and HIV/AIDS Policy (OIDP) update on 

behalf of the National Vaccine Program Office (NVPO), OIDP, and the Office of the Assistant 

Secretary for Health (OASH). Earlier in the month, the Associate Secretary of Health (ASH) 

named B. Kaye Hayes, MPA, as the Deputy Assistant Secretary for Infectious Disease and 

Director of the OIDP. Ms. Hayes has been the Acting Director of OIDP for the last 2 years. She 

comes to the position with over 25 years of experience in in the Office of the ASH (OASH). The 

first in-person meeting of the National Vaccine Advisory Committee (NVAC) since the pandemic 

started was convened on June 15-16, 2022 in Washington, DC. The ASH, Admiral Rachel 

Levine highlighted 2 issues of concern, immunization equity and health worker burnout and 

identified 2 new charges for NVAC. The first focuses on innovation. By September 2023, the 

NVAC is charged to develop recommendations to start innovations in vaccine development and 

related technologies. The second focuses on vaccine safety. By June 2023, the NVAC is 

charged to review vaccine safety systems and vaccine safety strategies to determine what 

should be maintained and what new strategies are indicated. The next NVAC meeting will be on 

September 22-23, 2022. 
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73

The Vaccines Federal Implementation Plan is currently under development and is nearing the 

finish line. The implementation plan is a complementary document to the National Vaccine 

Strategic Plan and the target audience is the federal agency. OIDP has incorporated public

comments received from the Federal Register into the draft implementation plan and it will be

reviewed by the Interagency Vaccine Group (IAVG) for their review before going through

interdepartmental and HHS clearance. The Implementation Plan is expected to be released by 

late summer. The National Vaccine Program Office (NVPO) is collaborating with the CDC and 

the OASH Office of Disease Prevention and Health Promotion (ODPHP) on converting

developmental immunization objectives to core measures in Healthy People 2030. The Healthy 

People 2030 sets data-driven national objectives to improve health and well-being over the next 

decade. The immunization objectives are aimed to improve adult immunization across the

lifespan and increase the number of pregnant women who receive the Tdap vaccine during 

pregnancy. 

ACIP Chair

Dr. Lee took a moment to thank all of ACIP’s colleagues from the federal agencies for their 

service, dedication, and continued focus on improving the health of the nation’s populations. 

She highlighted to the public that these people working in US federal agencies have been

working around the clock to protect the public, and it seems like there is no end to the series of 

crises that are coming their way. It is important to be mindful of burnout in the public health

sector just as much as there is concern about burnout amongst healthcare providers and staff.

While they continue to thank people, it is simply not enough. She expressed her hope that these 

systems will continue to be supported to ensure that the workforce is able to function. Based on 

her perspective, continuing at this pace is unsustainable.

CORONAVIRUS DISEASE 2019 (COVID-19) VACCINES

Session Introduction

Dr. Matthew F. Daley (ACIP WG Chair) introduced this session on behalf of the COVID-19 

Vaccines WG. He indicated that there have been more than 85 million reported cases of 

COVID-19 in the US since the start of the pandemic.56 Currently, the 7-day average is more 

than 100,000 cases per day. There have been over 1 million deaths from COVID-19 since the 

beginning of the pandemic. The 7-day average is currently 266 deaths per day.57 Based on data 

for the 12 months from April 2021 to April 2022, the rate of COVID-19 deaths by vaccination

status in people ≥5 years of age show that unvaccinated persons had a 10 times greater risk of 

dying from COVID-19 compared to people vaccinated with at least the primary series. This is 

one of the stronger pieces of evidence to emphasize the fact that COVID-19 vaccination is

effective at preventing death from COVID-19.58 Between December 14, 2020 – June 16, 2022, 

the percentage of children and adolescents who have received at least 1 dose of COVID-19 

vaccine was 69.7% of persons 12 through 17 years of age and 36.2% of children 5 through 11

years of age who had received 1 dose. This translates to 7.5 million people 12 through 17 years 

of age and 18 million children 5 through 11 years of age who have yet to receive any COVID-19 

vaccination.59 This is a stark reminder of all of the work that needs to continue to increase

vaccination coverage.

56 Source: COVID Data Tracker, https://covid.cdc.gov/covid-data-tracker/#trends_dailytrendscases Accessed 6/21/2022 57 CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#trends_dailydeaths Accessed June 21, 2022 58 https://covid.cdc.gov/covid-data-tracker/#rates-by-vaccine-status Accessed June 12, 2022 59 CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#vaccination-demographics-trends Accessed June 20, 2022 
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74

In terms of recommendations for COVID-19 vaccines, only the Pfizer BioNTech vaccine is

currently authorized by FDA and recommended by CDC for use in children 5 through 17 years

of age. With that in mind, the focus of this session was an update on the FDA-authorized

Moderna COVID-19 vaccine for children 6 through 17 years of age under Emergency Use 

Authorization (EUA) on June 16, 2022. This is a 2-dose Moderna COVID-19 vaccine primary 

series for administration in individuals 6 through 17 years of age. Also authorized was the third

primary series dose among individuals ages 6 through 17 years of age with certain kinds of 

immunocompromise.60

Recommendations following the emergency ACIP meeting on June 17-18, 2022 were as 

follows:

 A two-dose Moderna COVID-19 vaccine series (25μg) is recommended for children ages 6 

months through 5 years, under the EUA issued by the FDA.

(Two doses of 25μg Moderna COVID-19 vaccine: ≥4 weeks between Doses 1 and 2)

 A three-dose last Pfizer BioNTech COVID-19 vaccine series (3μg each) is recommended for 

children ages 6 months – 4 years, under the EUA issued by FDA. 

(Three doses of 3μg Pfizer-BioNTech COVID-19 vaccine: 3-8 weeks between Doses 1 and 

2; ≥8 weeks between Doses 2 and 3) 

The agenda for this session included presentations on the burden, prevalence, and trends of 

long-term sequelae of SARS-CoV2; updates on safety of COVID-19 vaccines in children and 

adolescents; a VaST assessment; safety and immunogenicity of Moderna 2-dose primary series

in children ages 6−17 years; the EtR Framework for Moderna COVID-19 vaccine in children and

adolescents ages 6−17 year; public comments; and a vote on Moderna COVID-19 vaccine in 

children and adolescents ages 6−17 years. 

Burden, Prevalence, and Trends of Long-Term Sequelae of SARS-CoV-2 

Sharon Saydah, PhD (CDC/NCIRD) presented on the burden, prevalence, and trends of the 

long-term sequelae of SARS-CoV-2. There are many terms used to refer to these conditions. 

The term “long COVID” is commonly used by patients who experience these problems. Similar 

terms include “long-hauler” or “long-haul COVID.” CDC and WHO use “post-COVID conditions.” 

NIH uses the term “post-acute sequelae of SARS-CoV-2 (PASC). The variety of terms reflects 

that there is still a lot to learn about the longer-term consequences of SARS-CoV-2 infection. 

While there might be minor differences in what is meant by each of these terms, they are often

used interchangeably.

The post-COVID conditions refers to a wide range of physical and mental health consequences 

present 4 or more weeks after SARS-CoV-2 infection. These conditions can occur in patients

with severe disease and also in patients who had mild or asymptomatic acute infection. It is 

important to remember that these groups are not mutually exclusive. A general framework for 

post-COVID conditions includes a definition that describes the variety of these conditions that 

can occur as a result of any severe illness, hospitalization, or treatment, such as post-intensive 

care syndrome. “Post-COVID conditions is an umbrella term for the wide range of physical and 

60 https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-moderna-and-pfizerbiontech-covid-19-vaccines-children
ACIP Meeting Summary June 22-23, 2022

75

mental health consequences, present for 4 weeks and beyond after SARS-CoV-2 infection, 

including for patients who had initial mild or asymptomatic acute infection. There are general 

consequences of illness and hospitalization, such as post-intensive care unit (ICU) syndrome 

and/or other complications of treatment or illness. Then there are processes that are likely more 

specific to SARS-CoV-2 infection that include system-specific effects such as newly diagnosed 

or identified neurological conditions, kidney damage or failure, diabetes, cardiovascular 

damage, or skin conditions. There also are symptoms that may have an unclear pathology and 

can involve a range of problems that can last for months after the acute infection or can even 

appear weeks or months after the acute phase has resolved. This unexplained group has 

features that are similar to other post-infectious syndromes. Included in this group are also 

ongoing symptoms following multisystem inflammatory syndrome in children (MIS-C). There are 

multiple mechanisms proposed for post-COVID conditions as depicted in this graphic:61

Many people who experience acute COVID go on to make a full recovery. Others may

experience long COVID. Some of the risk factors seem to include those that predispose people 

to more severe COVID, such as increased age, underlying medical conditions, and vaccination 

status. Post-COVID conditions may be explained by viral antigen persistence, systematic and 

tissue-specific inflammation, auto-immunity, microvascular dysfunction, or SARS-CoV-2 specific 

immune response. It is unknown whether these mechanisms differ among children. This is a list 

the commonly reported symptoms for post-COVID conditions. The ones noted in bold blue are 

symptoms that are more commonly reported by children:62

61 Peluso and Deeks. Early clues regarding the pathogenesis of long-COVID: Trends in Immunology (cell.com) 2022 62 https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html; Borch L et al. Long COVID symptoms and duration 

children. European Journal Pediatrics 2022
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There has been a wide range of reported problems of post-COVID conditions among adults. 

Based on self-report data using a mobile app, 13% of individuals with incident COVID-19 

followed up prospectively reported symptoms ongoing at 1 month and 2.5% reported ongoing 

symptoms at 3 months.63 When electronic health data were used among adults who were not

hospitalized for COVID-19, 7.7% had 1 or more of the 10 common post-COVID conditions 1 to 4 

months post-infection.64 The severity of acute COVID-19 illness also is associated with the 

occurrence of at least 1 symptom at 6 months.65 Among patients from the VA, non-hospitalized 

patients (44.5/1,000 patients) had a lower frequency of post-COVID conditions compared to 

those who were hospitalized (217.1/1,000 patients) and patients who were in the ICU with 

COVID had the highest occurrence (360.5/1,000 patients). 

Most patients recover from the acute illness within 4 weeks and the proportion reporting ongoing symptoms decreases 4-12 weeks. This is part of the reason why CDC considers illness

persisting beyond 4 weeks as warranting that initial clinical evaluation and supportive care. The 

proportion who report ongoing symptoms continues to decrease from 4 to 12 weeks, with 

improvement slowing around 12 weeks. When stratified by sex, the pattern is the same although 

a higher proportion of women report symptoms compared to men.66

Children present a unique challenge in assessing post-COVID conditions. Younger children 

particularly may have difficulty verbalizing symptoms, and they have a developmentally different 

understand of time. This makes it difficult to tease apart frequency, chronicity, and other details 

of their symptoms. Symptoms also may present in different ways with different children. There is 

not one specific symptom or even a cluster that is exclusive to long-COVID. An assessment of

these conditions also may be dependent on what is expected at different developmental

milestones. For example, sleep cycle changes might be perceived as developmentally accepted 

officially among very young children. Picky eating could be due to a loss of taste or smell or it

could be because children are often picky eaters. There also are numerous limitations in the

current research for post-COVID conditions among children, including varying time points from 

infection to the assessment, lack of control groups, and a small sample size for many reports.

Similar to adults, prevalence of post-COVID conditions can vary depending upon the setting and 

methods used. Symptoms lasting for 4 weeks or longer from infection are common among 

children and adolescents. The most common symptoms include headache or respiratory

symptoms (~7%), sleep disorders (~8%), fatigue (~9%), and mood disorders (~16%).67

In terms of results of non-hospitalized children who had mild or acute infections from a survey of

children in the United Kingdom (UK), the percent reporting positive SARS-CoV-2 tests ranged

from 20% in children 5−11 years of age to 30% in those 11−16 years of age. Among those who 

had a positive test, 7% had ongoing symptoms at 12 weeks and approximately 4% in the oldest 

age group had symptoms that impacted their activities of daily living for 12 weeks or longer.68 A 

prospective cohort study by Osmanov et al highlights the risk factors and symptoms

experienced by children who are hospitalized with COVID-19.69 Compared to the youngest 

children, those ages 6 to 11 years and those 12 to 18 years had the highest risk for post-COVID 

63 Sudre CH et al Nature Medicine 27, 626-631 (2021) https://www.nature.com/articles/s41591-021-01292-y 64 Chevinsky JR et al. Clinical Infectious Diseases 73 (S1) 2021 

https://academic.oup.com/cid/article/73/Supplement_1/S5/6257082?login=true 65 https://www.nature.com/articles/s41467-021-26513-3 66https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/articles/technicalarticleupdate

destimatesoftheprevalenceofpostacutesymptomsamongpeoplewithcoronaviruscovid19intheuk/26april2020to1august2021 67https://journals.lww.com/pidj/Fulltext/2022/05000/The_Challenge_of_Studying_Long_COVID__An_Updated.16.aspx; 

https://www.medrxiv.org/content/10.1101/2022.03.10.22272237v2 68https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/covid19schoolsinfect

ionsurveyengland/mentalhealthandlongcovidnovembertodecember2021 69 https://erj.ersjournals.com/content/early/2021/06/10/13993003.01341-2021 
ACIP Meeting Summary June 22-23, 2022

77

conditions. Children with a history of allergic diseases also were more likely to report postCOVID conditions compared to those without the history of allergies. Many of the common

symptoms experienced by adults also are experienced by children, with fatigue being the most 

common followed by sleep problems. Similar to adults, the duration of symptoms decreases 

over time.

A recently published study70 from the Distributed Research Network (DRN), with 42 participating 

healthcare systems and 2 health plans, compared patients who had a COVID-19 test between 

March and December 2020 and then received medical care for any reason in the 31 to 150 days 

after they were tested. Children with a positive SARS-CoV-2 test were more likely to receive the 

diagnosis for a new condition or symptom in the 5 months after their acute infection compared

to those who received a negative test. Comparing prevalence ratios for children who tested

positive compared to those who tested negative broken down by severity of illness, fatigue and 

shortness of breath were more common among children testing positive, particularly those who 

were hospitalized. The study also looked at several conditions that were more likely to be newly 

diagnosed in children testing positive compared to those testing negative. Type 2 diabetes was

more common among children hospitalized with COVID-19.

Children and adolescents with COVID-19 appeared to be at a higher risk for newly diagnosed 

diabetes. This was investigated further using electronic health data sources to examine newly 

diagnosed diabetes in children and adolescents.71 Retrospective cohorts were constructed

using IQVIA healthcare claims data from March 1, 2020 through February 26, 2021. Children

and adolescents with COVID-19 were compared to those without COVID-19 during the same 

time period, as well as to a group with acute respiratory illness (ARI) in the pre-pandemic

period. Children and adolescents with COVID-19 were 2.7 times more likely to be newly

diagnosed with any type of diabetes in the months following infection compared to those without 

COVID-19 or those diagnosed with other respiratory infections prior to the pandemic. Similar 

results have been observed in the adult population.

An unpublished analysis looking at the incidence of 12 conditions and 8 symptoms in close to 2 

million children with and without COVID-19 in a closed medical claims dataset found 9 postCOVID conditions and 4 post-COVID symptoms, most of which were rare or uncommon, that 

were more likely to occur among children with COVID-19 compared to those without COVID19.72 Children with MIS-C also appear to have a higher risk of ongoing symptoms following MISC. Continued difficulties are reported by 35% of the children and 21% of the children’s parents 

at 6 months. The number of systems affected at baseline is greater than those at 6 weeks and 6 

months, though a number of children and adolescents still have impact at 6 months.73 Most 

studies that have looked at post-COVID conditions occurring after vaccine breakthrough have 

focused on adults, though 2 published were identified that included adolescents.74 These

studies found that post-COVID conditions and symptoms were less likely to occur in 12 to 20 

weeks after infection among those previously vaccinated compared to the unvaccinated. While 

the exact mechanism through which vaccines may prevent long-COVID symptoms are 

unknown, vaccines can prevent post-COVID conditions by preventing infections.

70 Hernandez-Romieu AC et al. JAMA Netw Open. 2022 71 https://www.cdc.gov/mmwr/volumes/71/wr/mm7102e2.htm?s_cid=mm7102e2_w 72 US Commercial Medical Claims Data, March 1, 2019–September, 2021. Unpublished CDC data. 73 Penner J. et al. 6 month follow-up MIS-C. Lancet Pediatric 2021 74 Simon et al. Reduced Incidence of Long-COVID Symptoms | medRxiv 2022; Tarquet et al. Six-month sequelae of postvaccination SARS-CoV-2 infection| medRxiv 2022
ACIP Meeting Summary June 22-23, 2022

78

In summary, post-COVID conditions occur among children and adolescents with COVID-19

regardless of acute illness severity and appear to occur at higher frequency among those

who are hospitalized and adolescents. Remaining areas of uncertainty include the frequency,

severity, and duration of post-COVID conditions; understanding of the groups who might be

disproportionately impacted by post-COVID conditions; whether the associations with different

SARS-CoV-2 variants changes; and how post-COVID conditions may impact the daily activities 

and participation in school among children and adolescents.

Discussion Summary

Referring to Slide 6, Dr. Loehr observed that there was a large number of people who had 

symptoms after being hospitalized and in the ICU and asked whether there is a comparison 

group to know how many people in the ICU who did not have COVID-19 might have these 

symptoms. 

Dr. Saydah said that while she would have to look at the specific study to get the exact 

estimate, the analysis included adults. This analysis compared those who were mechanically

ventilated with these conditions and symptoms and identified an increase among the

mechanically ventilated for many of these conditions among adults compared to those who did 

not test positive for SARS-CoV-2.

Dr. Brooks found the odds ratio of 2.66 for new diagnosis of diabetes to be fascinating and

concerning. While the summary indicated that there is not information

on groups disproportionately affected, he assumed that there are race and ethnicity data on a 

lot of the patients in the studies presented. He asked if there is information on race and ethnicity 

in terms of the effects of long COVID in those populations. 

Dr. Saydah indicated that CDC is planning to publish more detailed results focused specifically

on race and ethnicity. Many of the data sources they have published on so far are missing some

of the components for race and ethnicity, which is one reason they have not published that yet. 

However, they are actively working on that. 

Dr. Daley asked what is known about vaccination among those who already have been infected

with respect to the trajectory of post-COVID conditions, which he raised because there will 

certainly be a number of children ≥5 and 5−17 years of age who were infected prior to

vaccination who may or may not have symptoms of post-COVID conditions at the time of

vaccination. 

Dr. Saydah responded that there has not been as much published looking among people who

have been infected and report symptoms who were then vaccinated. There is one study based 

on a survey in which individuals reported that their symptoms improved after vaccination. There 

is a recently published article from the UK from their Coronavirus Community Survey that looked

at this. As she recalled, they did not find a strong association of reduction in post-COVID

conditions among those who are vaccinated after infection compared to those who remained 

unvaccinated.

Dr. Sanchez said his understanding on variants was that there have been recent reports

showing that post-COVID symptomatology has been less with the new variants. He asked 

whether any assessments had been done on the timeline of when post-COVID symptomatology

was reported with more recent changes in the new variants. He also noted that there have been 

reports of post-COVID symptomology after vaccination.
ACIP Meeting Summary June 22-23, 2022

79

Dr. Saydah indicated that there has not yet been an opportunity to assess this, but do 

recognized that this is important. There are number of factors related to that as well. Moving out 

of this pandemic, individuals are more likely to report reinfections. How that might impact postCOVID conditions still needs to be assessed along with the effects of vaccinations. While CDC 

has received reports of post-COVID symptomology after vaccination, they have not seen 

anything specific based only on vaccination without any evidence of infection.

Dr. Shimabukuro added that think with respect to reports of the conditions described, CDC is 

aware of reports of people experiencing debilitating and long-lasting health problems after 

COVID-19 vaccination. In some cases, the clinical presentation of people suffering these health 

problems is variable and no specific medical causes for the symptoms have been found. Illness

is always disruptive and stressful, especially under these circumstances. CDC acknowledges 

that these health problems have substantially impacted the quality of life for some people and 

also have affected those around them and wishes for improvement in recovery. CDC will 

continue to monitor the safety of these vaccines and will work with partners to try to better

understand these types of AEs and the impact of disease in the development of these AEs. 

Dr. Poehling found it very convincing that COVID-19 in children is not a benign illness and that 

many children are suffering long consequences. Like Dr. Brooks, she impressed with the testpositive, test-negative studies showing in the subsequent 5 months that there is an increased 

risk of a new diagnosis of diabetes mellitus among those that have been hospitalized and that 

this also was found in the claims data. In terms of the medical claims data presented showing 

symptoms and conditions, myocarditis and pulmonary embolism were 2 that struck her. Also

what struck her was in regard to MIS-C in that 35% of children reported having symptoms 6 

months later.

Dr. Lee expressed appreciation for the work that CDC is beginning in order to understand what

may be a huge public health burden due to PASC or due to long-term complications of the

COVID-19 infection. She stressed that while there has been a heavy focus on the acute period, 

there is a lot more to learn about the chronic burden of this condition. She acknowledges that 

NIH has initiated the Recover NIH Initiative that is following cohorts over time in an effort to 

understand the national history of long-haul COVID. Looking at real-world data for an EHR 

cohort to try to understand and better characterize what PASC can help to improve the 

detection of PASC, understand the risk factors, and think about treatment and prevention in 

children better characterize and understand what needs to be done to address this emerging

public health burden. 

Updates on Safety of COVID-19 Vaccines in Children and Adolescents

Tom Shimabukuro, MD, MPH, MBA (CDC/NCEZID) provided updates on the safety of COVID19 vaccines in children and adolescents, including background on classic myocarditis and

myocarditis associated with mRNA COVID-19 vaccination; an update on myocarditis following 

mRNA COVID-19 vaccination with a focus on children ages 5–17 years, which included findings 

from the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink

(VSD); and data on comparative risk for myocarditis between the 2 mRNA COVID-19 vaccines, 

Moderna and Pfizer-BioNTech.
ACIP Meeting Summary June 22-23, 2022

80

With respect to classic myocarditis in children, there is usually an infectious cause that is 

typically viral or presumed to be viral, although infection with a pathogen is frequently not 

identified.75 It can be due to direct microbial infection of myocardial cells and/or ongoing

inflammatory response with or without clearance of the pathogen.76 Rare causes include

autoimmune, hypersensitivity, and giant cell myocarditis. Incidence in males is greater than

females starting after age 5 years.77 Previously, unrecognized myocarditis was identified as a 

cause of death in 8% of cases of sudden unexplained death in 1–17-year-olds78 and 9% of 

sudden death in athletes.79 It is common not identify a pathogen or possible infectious etiology

for myocarditis. In some case series, less than half of the time a specific infectious cause was 

identified.

In children, with the exception of very early in life when there may be genetic or other medical 

conditions playing a role, incidence is fairly low in early childhood and then begins to increase 

when children enter adolescence.80 Incidence peaks in adolescence and then gradually

decreases with age. Most cases are male, but that male-to-female predominance tends to even 

out in about middle age.81 This table shows the characteristics of myocarditis associated with

mRNA COVID-19 vaccination versus viral myocarditis:

* https://www.cdc.gov/vaccines/acip/meetings/index.html, https://www.cdc.gov/vaccinesafety/research/publications/index.html 

† Oster et al. JAMA. 2022;327:331-340. 

‡ Law et al. Circulation. 2021;144:e123-e135. Ghelani et al. Circ Cardiovasc Qual Outcomes. 2012;5:622-7. Kim et al. Korean Circ J. 2020;50:1013-1022. Messroghli et al. Am Heart J. 

2017;187:133- 144. Patel et al. J Am Heart Assoc. 2022;11:e024393.

¶ There are rare reports in the literature, especially from other countries, but it is unclear to what extent such cases were investigated

Moving now to data from VAERS, which is the national spontaneous or passive surveillance 

system that is co-managed by CDC and FDA. VAERS accepts reports from everyone 

(healthcare professionals, patients, parents, caregivers, manufacturers, et cetera) regardless of

the plausibility of the vaccine causing the event or the clinical seriousness of the event. The key 

limitation of VAERS is that as a passive surveillance system, it is generally not possible to 

determine cause and effect from VAERS data alone. In terms of reports to VAERS of

75 Bowles et al. J Am Coll Cardiol. 2003;42:466-72; Simpson et al. J Am Coll Cardiol. 2013;61:(10_Supplement) E1264; and Park et 

al. J Korean Med Sci. 2021;36:e232. 76 Caforio et al. Eur Heart J. 2013;34:2636-48, 2648a-2648d; Feldman et al. N Engl J Med. 2000;343:1388-98; and Guarner et al. 

Hum Pathol. 2007;38:1412-9 77 Arola et al. J Am Heart Assoc. 2017;6:e005306. 78 Burns et al. J Pediatr X. 2020;2:100023. 79 Maron et al. Circulation. 2009;119:1085-92. 80 Vasudeva et al. American J Cardiology. 2021. 81 Kyto et al. Heart. 2013.
ACIP Meeting Summary June 22-23, 2022

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myocarditis after Pfizer-BioNTech vaccination among children ages 5–17 years, there were 972 

preliminary reports of myocarditis to VAERS as of May 26, 2022. Of these, 214 remain under 

review, 123 did not meet the CDC case definition, and 635 reports were verified to meet the 

CDC case definition. To put that number into context, there have been 54.8 million total Pfizer

doses administered to children ages 5–17 years in the US during that surveillance period. Of the 

635 verified reports, 630 (99%) had a known time to symptom onset from vaccination, 

demonstrating a clustering of symptom onset within several days of vaccination. The 

overwhelming majority of these case reports in VAERS have onset within a week of vaccination.

Looking at VAERS reporting rates of myocarditis per 1 million doses administered after mRNA 

COVID-19 vaccination for Days 0–7 and 8–21 post-vaccination, observed reporting rates to

VAERS exceeded the expected background incidence, with the risk appearing to be 

concentrated in the first week after vaccination in both males and females. Reporting rates were

substantially higher in males compared to females and were higher for Dose 2 compared to

Dose 1 for both sexes. In the age group 5–11 years, there was an elevated observed to

expected ratio in the male Dose 2 0–7 day age-sex-dose strata. Otherwise, the reporting rates

in that age group were within background incidence.

CDC enhanced surveillance for myocarditis outcomes following mRNA COVID-19 vaccination in 

VAERS case reports includes 2 projects with 2 separate cohorts, children ages 5–11 years and 

people ages 12–29 years. Data were used from both cohorts to combine them into a 5–17 years

of age group.82 The purpose of this project was to assess functional status and clinical 

outcomes among individuals reported to have development of myocarditis after mRNA 

vaccination. This is a 2-component survey conducted at least 90 days after the onset of 

myocarditis symptoms that includes a patient or parent survey and a healthcare provider (HCP) 

survey. During the surveillance periods, (through November 2021 for 12–17 years and April 

2022 for 5–11 years), VAERS received 430 reports of myocarditis or myopericarditis after

vaccination in this age group that met CDC case definition and were at least 90 days postmyocarditis diagnosis. For the patient or parent survey, 190 surveys were completed, 128 were

unreachable on multiple attempts, 98 had no telephone contact information in the report, and 7 

declined to participate. Among the cardiologists or other HCP surveys, 226 completed a survey, 

120 were unreachable on multiple attempts, and 65 had no telephone contact information in the 

report. The main finding based on cardiologist or HCP assessment was that most patients 

appear to have fully or probably fully recovered from their myocarditis. Of the total patients, 226 

received a follow-up assessment by a cardiologist or other HCP regarding their myocarditis 

recovery. Among these patients, 80.1% were judged by their provider to be fully or probably fully

recovered.

In terms of the key findings from the CDC enhanced surveillance for myocarditis outcomes

following mRNA COVID-19 vaccination in VAERS case reports among children ages 5–17 

years of age, most patients who were reached with a patient survey reported no impact

on their quality of life and most did not report missing work or school at least 90 days after 

myocarditis diagnosis. Most HCP (80.1%) who completed surveys indicated that the patient was 

fully recovered or probably fully recovered. Of note, there was substantial heterogeneity in initial

and follow-up treatment and testing, and there did not appear to be a single test that was

indicative of recovery. The next step, which was occurring right now, is additional follow up with 

patients who were not yet fully recovered at the 90+ day survey and also with their HCP to 

further assess their recovery status at 12+ months.

82 https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/myo-outcomes.html 
ACIP Meeting Summary June 22-23, 2022

82

Moving on to findings from the VSD, which is CDC’s EHR-based system that is used for

surveillance and research, the VSD conducts Rapid Cycle Analysis (RCA), which is weekly 

sequential monitoring. The aims of the RCA are to monitor the safety of COVID-19 vaccines 

using prespecified outcomes of interest and to describe uptake of COVID-19 vaccines over time

among eligible VSD members. The VSD COVID-19 vaccine RCA pre-specified surveillance 

outcomes and the settings in which they are being monitored are shown on the following table:

Though the primary analysis in the VSD RCA is the vaccinated concurrent comparator analysis, 

it is looking at vaccinated patients only and cases in a risk interval compared to cases in a

comparison interval adjusted and matched by certain characteristics. For the pre-specified

outcome myocarditis/pericarditis, which is a combined outcome, the cases were verified using 

the CDC case definitions. Over 2 million total Pfizer primary series doses have been

administered to children ages 5–11 years during the surveillance period. There have been no 

statistical signals to date for myocarditis and pericarditis in the analysis in children ages 5–11

years. At this time, there are primary series vaccination only as there were not sufficient booster 

doses to do the analysis.

For people ≥12 years of age, including adults, statistical signals were detected for myocarditis 

and pericarditis for Pfizer-BioNTech and for both mRNA COVID-19 vaccines combined for 

primary series vaccination. Statistical signals were detected for myocarditis/pericarditis for both 

mRNA COVID-19 vaccines combined for the first booster dose. Based on data through May 28, 

2022 of cases with symptom onset of verified myocarditis/ pericarditis cases among children 

5−17 years of after either primary series dose of mRNA COVID-19 vaccines, there is a clear 

clustering of cases with symptom onset within Days 0−3 and Day 0−4 in the VSD data for the 

primary series.
ACIP Meeting Summary June 22-23, 2022

83

Verified myocarditis and pericarditis in the 0–7-day risk interval among male children ages 5−17 

years by age group and dose were split into 2 separate analyses, 5−11 years and 12−17 years

of age, with some subgroup analyses for the 12−17-year-old age group. The adjusted rate ratio 

is the statistic and there were no statistically significant elevated rate ratios in the age group 

5−11 years for myocarditis or pericarditis. However, the case counts are very small. For age 

group 12−17 years, there were elevated rate ratios following Dose 1, Dose 2, and the booster 

dose. The rate ratio was most elevated after Dose 2 at 160.52 (30.19 – 3343.73), which was

highly statistically significant. Looking at the subgroups within that age group and the age group 

16−17 years. There was an elevated rate ratio for subgroup within the age group 12−17 years of 

18.15 (1.62 – 558.73), which was statistically significant. For the age group 16−17 years, it was 

not possible to estimate rate ratio because there were no events in the comparison window. 

However, it was possible to estimate a lower bound of the 95% confidence interval, so after 

Dose 2 and after a booster dose were statistically significantly elevated. The case counts,

events, risk interval, and comparison interval were substantially lower for females than for males 

as might be expected. The adjusted rate ratios tended to be lower, and there were less

significant adjusted rate ratios. There was a statistically significant elevated rate ratio in females 

in the 12−17-year-old age group for Dose 2 and in the 12−15-year subgroup for Dose 2. Looking 

at straight VSD incidence rates of verified myocarditis and pericarditis in the 0−7 days following 

vaccination, there is a general trend that the incidence rate is higher in males compared to 

females and tends to be highest in Dose 2. While in some age and sex strata the incidence 

rates are higher for booster doses, there are relatively small case counts and very wide 

confidence intervals overlapping with the confidence intervals of the Dose 2 estimates. The level 

of care and status for the cases after the primary series and booster dose were quite similar, 

with most of these patients being admitted to the hospital. Most of them had relatively short 

lengths of stay of 1 or 2 days and 100% were discharged home.

Looking now at some findings on comparative risk of myocarditis between the 2 available

vaccines, Moderna and Pfizer, Dr. Shimabukuro reviewed some data that were presented 

previously to ACIP in October 2021 from VAERS.83 Reporting rates per million doses

administered among males tended to be higher for Moderna compared to Pfizer. Reporting

rates were substantially lower for females, but there was a similar trend in which the reporting

rates for Dose 1 or Dose 2 tended to be slightly higher for Moderna compared to Pfizer. Notably, 

those VAERS reporting rates are not a direct comparison. This was a side-by-side comparison

looking at the data individually by individual product.

A direct comparison was done using the VSD, the results of which were presented to ACIP 

during the February 4, 2021 ACIP meeting.84 Looking at case counts, onset, and incidence

of myocarditis cases following Pfizer and Moderna vaccine, the same clustering was observed 

in which the cases tended to cluster within several days after vaccination. There was a higher 

rate for Moderna compared to Pfizer in the Day 0−7 risk period. When a formal statistical

comparison was done for Moderna versus Pfizer, the statistic was a rate ratio. In all of these 

analyses regardless of dose and with both sexes combined, consistently elevated rate ratios are 

observed, although some of the confidence intervals on these point estimates were quite wide.

There was a statistically significantly elevated rate ratio when looking at either dose and for both 

sexes combined of 1.61 (1.02 − 2.54) that was statistically significant. This translates into 8

excess cases in the risk period per million doses for Modern compared to Pfizer. Looking at 

83 Presented during the October 21, 2021 ACIP meeting: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-10-20-

21/07-COVID-Su-508.pdf 84 Presented at the February 4, 2021, ACIP meeting: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-02-04/10-

COVID-Klein-508.pdf
ACIP Meeting Summary June 22-23, 2022

84

straight incidence rates of verified myocarditis and pericarditis in Days 0−7 following vaccination

with Pfizer or Moderna, the general trend was that there were higher post-vaccination incidence

rates per million doses administered for Moderna compared to Pfizer.

To summarize, the current evidence supports a causal association between mRNA COVID-19 

vaccines and myocarditis and pericarditis cases clustering within the first week of vaccination.

Myocarditis is a rare event following vaccination. CDC has verified 635 myocarditis case reports 

in children ages 5−17 years after 54.8 million Pfizer doses administered in this age group in the 

US. The risk appears greatest in adolescence in the age groups 16−17 and 12−15 years and is 

generally higher after Dose 2 compared to Dose 1 of the primary series and in males compared 

to females. In the VSD analysis, in the minority of age and sex strata, incidence is highest

following a booster dose. The reporting rate in VAERS of myocarditis following Pfizer in male

children ages 5−11 years after Dose 2 of the primary series is slightly elevated when compared 

to background rates. Otherwise, reporting rates are within background incidence. To date,

myocarditis/pericarditis has not statistically signaled in VSD RCA surveillance in children ages 

5−11 years. The available information suggests that most persons with myocarditis after mRNA 

COVID-19 vaccination recover from their myocarditis by 90+ days after diagnosis. In age groups

where product comparisons can be made, some evidence suggests that myocarditis and

pericarditis risk may be higher after Moderna than after Pfizer. However, the findings are not

consistent in all US monitoring systems.

As a reminder, CDC needs the help of state and local public health partners, partners in the 

healthcare community, and parents and caregivers who are enrolling children in v-safeSM in 

promoting v-safeSM in practice. HCP can provide the v-safeSM information and can direct patients 

to the v-safeSM website.85 Ideally, this should occur before vaccination. Parents need to enroll 

themselves before they can enroll children, but are strongly encouraged to enroll children into vsafeSM. CDC appreciates any assistance HCP can give in making sure that parents can 

caregivers are aware of the v-safeSM program. CDC’s Clinical Immunization Safety Assessment

(CISA) project is also available to US HCP who wish consultation on complex AEs following 

immunization.86

Vaccine Safety Technical Work Group (VaST) Assessment

H. Keipp Talbot, MD MPH (VaST Chair) Dr. Talbot presented the Vaccine Safety Technical 

WG (VaST) assessment of the data that just been presented, as well as some other data VaST 

was able to review. As a reminder, VaST’s objectives are to: 1) review, evaluate, and interpret 

post-authorization/approval COVID-19 vaccination safety data; 2) serve as the central hub for 

technical subject matter expertise from federal agencies conducting post-authorization

and approval safety monitoring; 3) advise on analyses, interpretation, and presentation of

vaccine safety data; and 4) provide updates to the ACIP COVID-19 Vaccines WG and the entire 

ACIP on COVID-19 vaccine safety. Since December 21, 2020, VaST has met 59 times to

review the vaccine safety data.

VaST reviewed data about the Pfizer-BioNTech vaccine in children 5−17 years of age and

compared data on safety monitoring from Moderna and Pfizer-BioNTech in the older age

groups. To put that into context, VaST reviewed US safety monitoring systems for PfizerBioNTech in children 5−17 years of age and comparative data on safety monitoring for Moderna 

and Pfizer-BioNTech vaccines in older age groups where comparisons were possible. From the 

85 https://vsafe.cdc.gov/en/; https://www.cdc.gov/coronavirus/2019ncov/vaccines/safety/vsafe/printresources.html 86 http://www.cdc.gov/vaccinesafety/Activities/CISA.html 
ACIP Meeting Summary June 22-23, 2022

85

v-safeSM system, VaST was able to obtain injection site and systemic reactions data. Among

49,392 v-safeSM participants ages 5–11 years who received Pfizer-BioNTech COVID-19 

vaccination reported to v-safeSM, the reactions are generally mild to moderate and most were 

reported the day after vaccination. Reactions were more frequently reported after Dose 2 than 

Dose 1. Patterns in these children are generally similar to those observed in older age groups.

In age groups ≥18 years of age where comparison between the mRNA vaccines was possible, 

injection site and systemic reactions are reported more frequently after Moderna than PfizerBioNTech COVID-19 vaccination.87

In terms of VAERS and the enhanced follow-up data, myocarditis following Pfizer-BioNTech 

vaccination, 54.8 million Pfizer BioNTech doses have been administered to children ages 5−17

years. Of these doses, 27.7 million were Dose 1, 23.3 million were Dose 2; and 3.8 million were 

first booster doses in children 12−17 years of age. VAERS has received 635 myocarditis case

reports that met the CDC case definition. Symptom onset clusters within several days of

vaccination, mostly within the first 0−7 days. Reporting rates are generally higher for males than 

females, especially for age groups 16−17 and 12−15 years. Differences by sex in children ages

5−11 are much less pronounced. The reporting rate of myocarditis in male children ages 5−11

years after Dose 2 of the primary series is slightly elevated when compared to background

incidence. Otherwise, reporting rates for both sexes is similar to background incidence.

Regarding enhanced follow-up of myocarditis cases,88 most patients reached for follow-up 

reported no impact on quality of life or missing school or work. Most HCP indicated that the 

patient fully recovered or probably fully recovered.

With regard to information on Pfizer-BioNTech vaccination in children 5−11 years of age in the 

VSD, among approximately 878,000 children ages 5−11 years of age VSD, 41% had completed 

the Pfizer BioNTech vaccine primary series and no statistical signals were identified in the 21-

day risk interval for any outcomes identified.89 Where data for both vaccines, Moderna and 

Pfizer-BioNTech vaccines were compared for the outcome of myocarditis/pericarditis in Days 

0−7 post-vaccination among persons 18−39 years of age. Both vaccines are associated with

increased risk of myocarditis/pericarditis in the 0−7 days post-vaccination, particularly after 

Dose 2. No noticeable differences have been observed in the level of care and clinical status

between the cases following Moderna or Pfizer vaccination. Most cases were hospitalized and

had stays of 1 day or less. Direct head-to-head comparison in ages where possible provides 

evidence that the risk of myocarditis and pericarditis may be higher after Moderna than after 

Pfizer vaccination.90

The FDA shared data from its Biologics Effectiveness and Safety System (BEST) system on 

Pfizer-BioNTech vaccination in children 5–17 years of age showing that among 5.4 million 

Pfizer-BioNTech doses in this age group, there were no statistical signals among children ages 

5−11 years. However, there were statistical signals for myocarditis/pericarditis among children 

12−15 and 16−17 years of age.91 Still using the BEST system, myocarditis/pericarditis in Days 

1−7 post-vaccination among persons 18–25 years of age were compared between Moderna

and Pfizer vaccination. A large study in several US administrative health plan claims databases

of people aged 18−64 years of age92 found that the occurrence of myocarditis/pericarditis after 

87 Rosenblum et al. Lancet ID 2022. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901181/ 88 Shimabukuro, ACIP presentation, June 23, 2022 89 Through April 2022; Shimabukuro, ACIP presentation, May 19, 2022 90 Klein, ACIP presentation Feb 4, 2022 https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-02-04/10-COVID-Klein508.pdf 91 Wong, FDA’s VRBPAC presentation, June 14, 2022. https://www.fda.gov/media/159224/download 92 Wong et al, Lancet 2022
ACIP Meeting Summary June 22-23, 2022

86

COVID-19 mRNA vaccination was rare. There were 411 events per 16.9 million doses of PfizerBioNTech and 10.6 million doses of Moderna. The 95% confidence intervals for the incidence

rate ratio comparing the brands ranged from 0.80 to 1.94. The risk was highest in men aged 

18−24 years of age 1−7 days after Dose 2. Among men 18−25 years of age, there was an 

elevated rate ratio for Moderna compared to Pfizer-BioNTech vaccination, but this was not 

found to be statistically significant like in other systems.93

To summarize the VaST assessment of the data from v-safeSM, VAERS, VSD, and BEST, there 

is a risk of myocarditis/pericarditis after both mRNA COVID-19 vaccines. Most cases had

prompt improvement in symptoms. Follow-up surveys suggest most fully recovered that most 

people fully recover from myocarditis. Risk has been observed in adolescents and adults.

Potential risk is under assessment in children <12 years of age and this age group will continue 

to be monitored. Continued monitoring and natural history studies are needed for

myocarditis/pericarditis following mRNA COVID-19 vaccinations in order to better understand 

rates, outcomes, risk factors, and mechanisms. Monitoring data for Moderna vaccine are

available for persons ≥18 years of age who received a 100 ug dose. Currently, the EUA is for a 

100 ug dose for those 12−17 years of age and a 50 ug dose for those 6−11 years of age. It is 

unknown whether the lower dose of 50 ug will pose a lower risk.

VaST will continue to review safety data for multiple US safety systems, in specific age groups, 

and after primary series and booster doses. In addition, VaST will continue to collaborate with

global vaccine safety colleagues on key issues and will continue to provide updates to the ACIP 

COVID-19 Vaccines WG and ACIP during future meetings.

Discussion Summary (Shimabukuro & Talbot)

Dr. Poehling observed that data from Canada showed that persons who received the primary

series doses ≥8 weeks apart had less evidence of myocarditis. She wondered whether there 

were any plans to evaluate this through the US surveillance systems.

Dr. Shimabukuro responded that information from the VSD shows that adherence to the

schedule in the US is quite high. Most persons get their second dose of the primary series on or 

about 21 days after the first dose as per the recommendations. Canada has a somewhat 

different situation because there are actually alternate recommendations on dosing for the

booster. Canada had more data to make that assessment. In the US, there are limited data to 

make that assessment, given that adherence to the recommended schedule is quite high. As 

data continue to be collected, it may be possible to get more information on some of these

alternate intervals between the first and second doses. However, there is currently not sufficient 

information to assess that.

Dr. Long noted that the only surprise to her was the occurrence of myocarditis/pericarditis 

following a booster, which she anticipated would be lower. She wondered if perhaps it is 

becoming more common following a booster dose and with the prevalence of Omicron.

Dr. Shimabukuro indicated that the in general, the data are showing that the reporting rates and 

the risk in terms of the rate ratios are lower after a booster dose compared to Dose 2. This is 

less clear in terms of incidence rates. The general trend is for lower risk after the first booster 

dose compared to Dose 2. There may be multiple reasons for that, one of which may be the 

interval. In some cases, there is a lower dose for the booster dose. There might be some

93 Wong, FDA’s VRBPAC presentation, June 14, 2022. https://www.fda.gov/media/159224/download 
ACIP Meeting Summary June 22-23, 2022

87

selection out of people who got myocarditis after Dose 2 who do not receive a booster dose. 

CDC will continue to monitor safety of additional booster doses and because 

myocarditis/pericarditis has signaled and a causal relationship has been established, that will be 

a focus of the ongoing surveillance. Based on the current data, there does not appear to be 

greater for the booster dose after Dose 2. If anything, the general trend seems to be a lower risk

after at least the first booster compared to Dose 2.

Dr. Klein pointed out that in addition to the rate ratios appearing to be numerically lower after the

booster dose in the VSD analyses, it has been after the second dose. All of the analyses are

tightly adjusted for calendar time. Issues such as Omicron are taken into account when the 

booster dose analyses are done.

Dr. Sanchez emphasized that there seemed to be 2 issues, interval and dosing, which may be 

important in the case of children 5−11 years of age in terms of the perceived fewer cases in

Pfizer versus Moderna recipients. Moving forward, it will be important to assess how this risk 

can be further minimized in the age group that is at highest risk. As he recalled, not vaccinating

those with a prior myocarditis/pericarditis report is stated as a precaution not a contraindication

and he wondered if CDC is keeping track of that as well to determine how many people have 

been vaccinated post-myocarditis/pericarditis.

Dr. Shimabukuro indicated that CDC is aware of some case reports of persons with myocarditis

being vaccinated. While he was not aware of any recurrence of myocarditis in a vaccinated

patient with prior myocarditis, he would say it is probably a fairly rare occurrence. He did not 

think there was sufficient data to assess risk right now for essentially what would be a “rechallenge.” Regarding the younger age groups, he referred to Slide 4 in his presentation. With 

respect to children 5−11 years of age, vaccine-associated myocarditis tends to follow the same

general trend as classic myocarditis. Children 5−11 years of age tend to be a low-risk group for 

myocarditis in general.

Ms. Bahta that with regard to the earlier discussion about long-haul COVID-19, there has been 

a cluster in her area of Minnesota of people who are developing chronic symptoms after

vaccination. Perhaps long-haul COVID is not rising to the level of creating a signal, but it 

certainly seems to be a distressing pattern for the people experiencing these chronic long-term 

symptoms after they have been vaccinated. She asked whether more could be said about this.

Building on what he said earlier, Dr. Shimabukuro indicated that CDC is aware of reports of

people experiencing debilitating and long-lasting health problems, acknowledges that this can 

be disruptive, stressful, and can substantially impact the patient and those around them, and 

wishes for improvement and recovery. With respect to CDC’s systems and monitoring, most

AEs reported after COVID-19 vaccines are mild and transient events in general such as 

injection site and systemic reactions. CDC’s safety and monitoring systems are robust and have 

identified rare, serious events and unanticipated conditions like thrombosis with

thrombocytopenia (TTS) and myocarditis. But these systems are dependent on identifying

patterns and specific diagnoses or patterns and symptoms following vaccination. That is how 

TTS and myocarditis were identified. Some patients who become ill experience a wide range of 

symptoms that can make diagnosis and treatment for their condition challenging, and this 

understandably can be frustrating for patients, families, and their doctors. It also makes it

difficult to identify whether these illnesses are linked to vaccination. Both CDC and FDA use

methods that can identify unexpected patterns or diagnoses or symptoms, but it still requires a 

detectable pattern. Without a specific diagnosis, which is what they are dealing with in many

cases, it is much less that these specific patterns will be found in the surveillance systems.
ACIP Meeting Summary June 22-23, 2022

88

COVID-19 vaccine safety monitoring will continue. CDC will continue to work with partners (e.g., 

within the federal government, HCP, and provider organizations to better understand these 

types of AEs.

Dr. Daley asked what the long-term plans are to study the biology or the pathophysiology of pf 

myocarditis to be better able to reduce it in the future. Related to that, he asked whether Dr. 

Beigel or others could help him understand the exact dose difference between the Moderna and 

Pfizer vaccine platforms. They were hearing 25, 50, or 100 micrograms for Moderna or 3, 10 or 

30 micrograms for Pfizer, but it was not clear whether that was an apples-to-apples

measurement or it includes other things that come along with the mRNA so that it is not an 

exact comparison of dose amount.

Dr. Beigel indicated that he was not aware of any studies specifically evaluating the

pathophysiology, but said he would delve into that and would you a written response to make 

sure he does a comprehensive review of all the possible paths for that.

Dr. Oliver added that fundamentally in terms of a Pfizer vaccine at 30 μg compared to a 

Moderna vaccine at 100 μg, there are different components such as the spike protein and lipid 

nanoparticles. They are not a one-to-one comparison in that the Moderna vaccine at 100 μg in 

not expected to be 3 times as high as Pfizer at 30 μg. They both have been shown to elicit 

similar levels of antibodies and efficacy.

In terms of the availability of a consultation, Dr. Poehling asked whether CISA’s work could help 

to understand what is occurring with long-COVID.

Dr. Shimabukuro clarified that the CISA clinical consult service is available to consult with US

HCP who request a consultation on a specific patient, largely in terms of how to manage the

patient moving forward and issues about additional vaccination. The broader issue of analyzing 

this condition is that it is difficult to hone in on a certain pattern in the absence of diagnoses and 

it makes monitoring quite difficult. He emphasized that CDC recognizes and acknowledges that

there are reports of people experiencing these conditions. The presentation can be quite 

heterogenous and variable, which makes it difficult to assess whether what role, if any,

vaccination may have played. CDC is certainly exploring ways to further assess these

conditions and work with partners, particularly healthcare partners, to better understand these 

kinds of AEs.

Ms. McNally asked Dr. Shimabukuro to remind ACIP of the impact of other countries’ safety

monitoring systems in the VaST review and in the ISO’s work to monitor safety, especially as it 

relates to myocarditis and pericarditis.

Dr. Shimabukuro indicated that CDC has regular contact with international partners. In 

particular, they have spoken with their colleagues in Canada and have been briefed by

colleagues in Israel on VaST calls. Data from multiple sources outside of the US are certainly 

taken into consideration. With respect to myocarditis, the data have been remarkably consistent

across systems and across other public health and regulatory agencies that are looking into this 

condition. International partners, regulatory and public health agencies, and academic 

institutions are regularly invited to brief the WG in order to gain perspective on what is occurring 

in states and outside of US safety monitoring systems.
ACIP Meeting Summary June 22-23, 2022

89

Dr. Duchin (NACCHO) observed that about half of the reports of myocarditis have been followed 

up with the parent and/or the HCP. He wondered what the implications were of following up only 

half of the cohort in terms of potential limitations on the interpretation of the cohort that has been 

followed up.

Dr. Shimabukuro said he did not have the information available right then on how the individuals

or HCP who could not be reached for follow-up or who declined to participate may compare to 

the individuals in the cohort who decided to participate in the survey. While he did not believe

that there were any substantial differences, he indicated that he would check on that and report 

back. With respect to the project to follow-up on the long-term outcomes in these case reports, 

CDC made every effort to try to reach out to individuals and HCP providers in advance to try to

maximize the response rate. In addition, they are engaging in longer-term follow-up at 12+ 

months and are reaching out to patients they were not able to contact during the first iteration of 

interviews during which they spoke with providers but did not get a chance to contact the actual 

patient or the parent.

Safety & Immunogenicity of Moderna 2-Dose Primary Series in Children Ages 6-17 Years

Rituparna Das, MD, PhD reminded everyone that in January 2020, Moderna’s 100 μg 2-dose 

primary series was approved in the US for adults ≥18 years of age after being authorized for 

emergency use since December of 2020. mRNA-1273 is authorized or approved in 86 countries

for a primary series worldwide and in 48 countries for boosters. This vaccine is now authorized

for children and adolescents 6−17 years of age outside of the US. For adolescents, 100 μg 2-

dose primary series is available in 42 countries. Approval has been received for the 50 μg 2-

dose primary series in children 6−11 years of age in 40 countries. More than 6.4 million

adolescents and 300,000 children have been fully vaccinated with a primary series of mRNA1273 outside of the US.

The purpose of this presentation was to discuss the use of mRNA-1273 as a 2-dose primary 

series for the prevention of COVID-19 caused by SARS-CoV-2 in adolescents 12−17 years of 

age and children 6−11 years of age. The proposed 2-dose primary series of the 100 μg for

adolescents and 50 μg for children 6−11 years of age are to be administered 1 month apart. The 

pediatric development program has 2 clinical studies. Study 203 in adolescents 12−17 years of 

age enrolled more than 3,700 participants, nearly 2500 of whom received mRNA-1273. Study

204 enrolled children 6−11 years of age among whom more than 3,300 children received 

mRNA-1273 at the 50 μg dose. There are 5,800 children total in the whole age group, which

established a substantial pre-licensure safety database. In terms of the median safety follow-up 

times for the studies, Study 203 was blinded and placebo controlled. This trial had about 11.1 

months of follow-up at the time of the data cut. Study 204 that investigated the lower doses

started as an open-label dose escalation design. The second part of the study was the placebocontrolled trial. There are 8 months of follow-up from the open-label portion and 5.6 months of 

follow-up for the larger study cohort.

In both studies, you know, safety was a primary objective. Specific safety endpoints included 

local and systemic adverse reactions that were collected for 7 days post-vaccination. All 

unsolicited events were captured for 28 days. Serious, medically attended, and AESIs were 

followed throughout the whole study. Myocarditis emerged as a post-authorization safety signal. 

This occurred when both studies already were ongoing. Moderna updated its Fact Sheets,

Investigative Brochures, and Informed Consent Forms to increase awareness among

investigators, study participants, and parents. These conditions also were specified as AESI to 
ACIP Meeting Summary June 22-23, 2022

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ensure that they would be reported rapidly. To further increase the sensitivity of detection, a 

script was added to ask about the CDC symptoms of myocarditis and pericarditis during safety 

follow-up calls on Day 8 and Day 36 post-vaccination. The clinical database also was actively

reviewed for any symptoms that could have reflected myocarditis. All potential events were

submitted to an independent Cardiac Event Adjudication Committee (CEAC) that was

composed of expert cardiologists. There were 2 overlapping approaches to evaluate all

unsolicited AEs for any potential cases for myocarditis or pericarditis. Standard MedDRA 

queries were applied first and a specific algorithm was generated using the MedDRA terms 

included in the CDC case definitions. Ongoing post-authorization safety studies continue to

capture myocarditis and pericarditis as AESIs. 

VE was the primary objective in both of these studies. It was successfully inferred by meeting 

the pre-defined immunogenicity criteria that were agreed upon beforehand with the FDA. In 

each age group, immune responses were compared to the subset of adults 18−25 years of age 

from Study 301 that demonstrated efficacy against SARS-CoV-2. The younger adult subset was 

chosen to ensure sufficiently high immunogenicity from the inference of VE, given that immune

responses in younger adults have been observed to be higher than those in older adults. There 

were 2 non-inferiority criteria. The lower bound of the GMT ratio had to be ≥0.67 and the point 

estimate had to be ≥0.8. FDA requested a point estimate of ≥1.0 if doses <100 μg were 

selected. Second, the lower bound of the difference in the seroresponse rate, which is a 4-fold 

rise baseline, had to be > -10%. An efficacy evaluation was a pre-specified secondary objective 

in the trial.

As in the 301 study, 2 case definitions were applied 1) the CDC case definition, which requires 1 

systemic or respiratory symptom; and 2) the Study 301 case definition, which requires 2 

systemic symptoms or 1 respiratory symptom. Both case definitions required an RT-PCR that is 

positive for SARS-CoV-2. The CDC case definition was considered primary since children

tended to have less severe symptoms of COVID-19 than adults. Given that the studies were 

conducted during different periods of the COVID-19 pandemic, an efficacy follow-up was

performed. During Study 301, the original strain was almost exclusively circulating. The efficacy 

follow-up for adolescents was conducted when the original strain and Alpha variant were 

circulating. The cohort of children 6−11 years of age were followed when the Delta variant was

dominant.94

Now to review the safety, immunogenicity, and efficacy data from the Study 203 in adolescents

12-17 years of age. Aa total of 3,732 adolescent participants were randomly assigned 2:1 to

receive either 100 μg of mRNA-1273 or placebo. The dose level and schedule were identical to 

the adults in Study 301. The interval between doses was 1 month apart, with which study

participants were extremely compliant. Participants received a booster dose subsequently and 

are being followed for an additional 12 months. Overall, the 2 groups were well-balanced

demographically.

95

In terms of solicited local AEs within 7 days after Doses 1 and 2, injection site pain was the most

commonly reported solicited local AE after either injection. The majority of the reported events

were Grade 1 or 2 in severity and lasted for a median of three days. The reactions were

reported approximately at the same frequency after Doses 1 and 2 and were reported more 

frequently in the mRNA-1273 group than in the placebo group. The reactions also were reported 

more frequently in adolescents than in young adults. The majority of the systemic reactions also 

94 https://covid.cdc.gov/covid-data-tracker/#trends_dailycases 95 Ali et al., NEJM 2021
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were Grade 1 or 2 in severity, with a median duration of 2 days. Consistent with the established

profile of mRNA-1273, systemic reactions were reported more frequently post-Dose 2 than postDose 1. The reactions tended to be reported as a similar to lower rate in adolescents than in 

young adults, which suggests that the reactogenicity profiles at the 100 μg dose in adolescents 

is acceptable and generally comparable to young adults.

In terms of unsolicited AEs recorded up to 28 days after vaccination, 21% of participants in the 

mRNA-1273 group and 16% of the placebo group reported unsolicited AE, and 13% and 6%,

respectively were considered by the investigators to be potentially vaccine related. This was 

primarily driven by reports of lymphadenopathy and injection site reaction. The percentage of 

medically attended adverse events (MAAEs) was similar between the 2 groups, and there were 

very few SAEs, severe AEs, or AEs leading to discontinuation. No vaccine-related SAEs or 

deaths were reported.

Long-term safety data are now available for a median follow-up of 11.1 months after Dose 2 for 

the original vaccine recipients. The safety profiles were typical for this age group and no new

safety concerns were identified. The most commonly reported MAAE was COVID-19, although

importantly, there were no SAEs of COVID-19. The increased rates of COVID-19 likely reflect

the Omicron surge and the fact that these participants were nearly a year out after vaccination

when a number of these events were reported. There were no confirmed cases of myocarditis 

or pericarditis in the long-term follow-up assessments.

Given the importance of these events, Dr. Das also discussed Moderna’s post-authorization 

surveillance since mRNA-1273 is authorized for adolescents in 42 countries worldwide. These 

data come from the Moderna Global Safety Database and are analyzed by each cohort’s dose 

number and gender. Consistent with other reports in the published literature and what was

discussed throughout regarding the higher reporting rate for myocarditis after Dose 2 in males, 

the highest rates were in males 18−24 years of age after Dose 2 with approximately 43 cases 

per million doses. The rate for the adolescents was 13.3 cases per million doses. For 

comparison, Block, et al96 recently reported the incidence of myocarditis after SARS-CoV-2 

infection. The incidence of myocarditis in adolescent and young adult males diagnosed with 

SARS-CoV-2 is over 500 cases per million, suggesting that the rate is substantially higher than 

after Dose 2 of mRNA-1273.

For the primary effectiveness objective, the primary hypothesis was to demonstrate that immune

responses in adolescents were non-inferior to the young adult cohort in Study 301 study where 

efficacy of the vaccine against COVID-19 was demonstrated. The first criterion was a GMT ratio

in the adolescent group over the young adult group. The observed GMT ratio was 1.1 with a 

lower limit of 0.9. The second criterion was the group difference in seroresponse rate. The rate 

was 98.8% in the adolescent group and 98.6% in the adult group, with a difference of 0.2 

percentage points and a lower limit of -1.8. Therefore, the primary effectiveness hypotheses

were met. VE was evaluated as a secondary objective. In terms of the case definition used by 

the CDC, there were 7 cases reported in the placebo group and 1 reported in the mRNA-1273 

group, for VE of 93.3%. When the more stringent case definition from Study 301 was used, 

there were 4 cases reported in the placebo group and 0 cases in the mRNA group, with an 

observed VE of 100%.97

96 Block, J. P. et al. Cardiac Complications After SARS-CoV-2 Infection and mRNA COVID-19 Vaccination — PCORnet, United 

States, January 2021–January 2022. MMWR Morbidity Mortal Wkly Rep 71, (2022). 97 Ali et al, NEJM, 2021
ACIP Meeting Summary June 22-23, 2022

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Study 20498 regarding the safety, immunogenicity, and efficacy of mRNA-1273 in children 6−11 

years of age was conducted in 2 parts. The first part was to identify the correct dose of mRNA1273 in children 6−11 years of age and the second part was to evaluate that dose in a 

randomized placebo-control study. In part one, 2 doses of mRNA 1273 were evaluated in an 

open-label design. The lower 50 μg dose was selected as it showed an acceptable tolerability

profile and demonstrated a high likelihood of meeting the pre-specified immunogenicity success 

criteria. After the first part was completed, a DSMB meeting occurred to ensure the committee’s

concurrence with the selected dose. The second part of the study was designed to randomize 

the children in a 3:1 ratio to receive either mRNA-1273 or a saline placebo. The data presented 

during this session focused on the randomized phase of Study 204, which evaluated the 2-dose 

50 μg primary series in children 6−11 years of age. All study participants will be followed for 12 

months after their last dose of vaccine. The demographics for the children ages 6−11 years 

were well matched among vaccine and placebo recipients. The mean age in both age groups 

was 8.5 years, with a good balance of males and females.

In terms of solicited local reactions in children 6−11 years of age, pain was the most common 

event with similar rates and severity following Dose 1 and Dose 2. Most local AEs, including 

pain, were Grade 1 or 2 and there were few Grade 3 reactions. The median duration of local 

adverse reactions in this age group was 2 to 3 days. Fatigue and headache were the most 

commonly reported systemic adverse reactions. Reporting rates for fatigue and headache were 

similar to those seen in adolescents and young adults. The rest of the systemic adverse

reactions were reported at a lower rate in the older children compared to the young adults. The 

rates of systemic adverse reactions post-Dose 1 were similar to placebo. Among vaccine

recipients, systemic adverse reactions were more frequently reported post-Dose 2 than postDose one. Events were mostly Grade 1 or 1 in severity, with a median duration of 2 to 3 days.

Regarding unsolicited AEs reported up to 28 days after any injection in children 6−11 years of 

age, 30% of participants in the vaccine group compared to 25% in the placebo group reported

any unsolicited adverse reactions. The imbalance in AEs was primarily driven by local AEs in

axillary swelling or tenderness, similar to what was seen in adolescents. MAAEs were similar 

among the 2 groups at 13% and 14%, and there were no SAEs considered related to 

vaccinations by the investigators. There were no fatal AEs, events of MIS-C, or 

myocarditis/pericarditis.

Long-term safety data are now available for a median duration of 5.6 months among the original 

vaccine recipients. Looking at cumulative incidence of unsolicited AEs through this time, no new 

safety signals were observed and there were no deaths, related SAEs, or AEs of MIS-C or 

myocarditis in this original vaccine group. Safety data also were collected on the original

placebo recipients who got vaccine in the crossover. There was 1 related SAE after vaccination. 

This was a case of ileus reported in a participant with a complex gastrointestinal (GI) medical 

history from the placebo crossover group.

Immunogenicity was a primary objective of the study. After the 2-dose 50 μg primary series in 

children 6−11 years of age, the GMT was 1,610 in the older children compared to 1,300 in the 

young adults. This resulted in a GMT ratio of 1.2, which met the prespecified non-inferiority 

criteria. The seroresponse rate was 99.1%, which also met the non-inferiority seroresponse

criteria. The efficacy assessment was a secondary objective. Assessment of placebo-controlled 

VE in children 6-11 years of age group was limited due to the authorization of another COVID19 vaccine. Per the study protocol, participants were unblinded then to offer them access to

98 Creech et al., NEJM, 2022
ACIP Meeting Summary June 22-23, 2022

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mRNA-1273. The number of COVID-19 cases in the per protocol population post-Dose 2 with a 

1.8 median follow-up time was small and did not allow for meaningful assessment. Dr. Das 

presented the assessment that was conducted in the mITT population, which was based

on a higher number of cases because the mITT population allowed counting of cases 14 days 

after post-Dose 1. The mITT calculation is typically a more conservative calculation because it 

does not require a follow-up time after the whole vaccine dosing and it allowed an additional 

month for case accrual. The overwhelming majority of study participants in the mITT cohort

received their second dose of vaccine. Efficacy was high at 88% using the broad CDC definition 

and was 92% using the more stringent Study 301 definition. Given that this trial was conducted 

during the Delta period, this represents direct efficacy against the Delta variant. The immune 

response of mRNA-1273 has been remarkably consistent across each cohort despite 

administering lower doses to children. Across the pediatric age group, the ratio of immune 

responses compared to young adults 18−25 years of age ranged from 1.01 to 1.28, successfully 

meeting all of the immunogenicity hypotheses.

To summarize, the totality of data from the pediatric development program in these age groups 

from 8,000 children, 5,800 of whom received vaccine and had a median duration of follow-up of 

over 5.6 months, supported the benefits of mRNA-1273 in school-aged children and 

adolescents and that these benefits outweigh the known and potential risks. mRNA-1273 was 

generally well-tolerated, with a safety profile consistent with that observed in young adults. No 

new safety concerns have been identified. Moderna’s pediatric studies were designed to meet 

the FDA criteria for inference of VE compared to young adults as the VE in a population of 

adults already has been demonstrated. In both age groups, the co-primary immunogenicity

hypotheses were met. In addition, there was evidence of efficacy against COVID-19 conferred 

by mRNA-1273 ranging from 88% to 100% during original, Alpha, and Delta variant circulation.

Moderna has established a robust plan to continue to evaluate safety and effectiveness in its 

clinical trials and in post-authorization studies.

Discussion Summary

Dr. Poehling requested additional information about any Grade 4 AEs that were detected in 

either cohort.

Dr. Das indicated that there were no Grade 4 events for either local or solicited systemic AEs. In 

the adolescent group, there were no Grade 4 local solicited AEs. There were 4 Grade 4 

systemic AEs. Of those, 3 occurred in vaccine recipients and 1 was in a placebo recipient. The 

vaccine recipient had events of fever, headache, nausea, and vomiting.

Referring to Slide 18, Dr. Daley requested additional information about the data source in terms 

of strengths and limitations. 

Dr. Das indicated that these data were from Moderna’s Global Safety Database. All global

reports for myocarditis are contained in this database. The denominator is the estimated per 

million doses administered by the different age groups. The limitations are that it is passive 

reporting from patients’ parents and providers. Moderna attempts to get as much information on 

the cases as possible, but are probably not as good as the CDC assessment are at times in 

terms of being able to get all of the detailed follow-up, which is a challenge for everyone.
ACIP Meeting Summary June 22-23, 2022

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Referring to Slide 32, Dr. Daley asked what was being measured when in the 100 μg in terms of 

whether that was just mRNA or mRNA plus other elements and how does that translates into

how a 50 μg dose compares to a 100 μg dose and whether post-vaccination myocarditis has 

any sort of dose response. 

Dr. Das explained that the mRNA contents ratios are exactly as would be expected for the 

mRNA contents. What is being measured is only the mRNA. In terms of whether postvaccination myocarditis has any sort of dose response, it would be very hard to opine on that

based on the dataset.

Dr. Sanchez emphasized that it is critical to know what exactly is being measured and to 

understand more about the pathogenesis in order to try to prevent it. He asked if there is a 

standard measurement of mRNA content or if each company or each laboratory measures 

mRNA differently. It is not clear if/how Moderna’s 50 μg and 100 μg can be correlated to Pfizer’s 

30 μg. 

Dr. Das indicated that Moderna has a validated method for mRNA measurement, which is how

they are reporting their doses. She was not aware of other vaccine manufacturer’s 

measurement methodology. Perhaps it would be better for FDA to comment on this.

Dr. Sanchez recognized that it has been stated that mRNA disappears quickly, but he inquired 

as to how long spike proteins have been detected in patient’s serum or tissues following mRNA 

vaccination and what the molecular weight is of the spike protein that human bodies produce—

with respect to transplacental transfer as well.

Dr. Das indicated that the detectability of spike protein and mRNA have been assessed. The 

mRNA degrades quite quickly, and spike protein availability is on the order of days, but less 

than a week. She will confirm this with their toxicology folks as well. The molecular weight is 

what would be expected for the full spike. 

Dr. Daley asked Dr. Das to comment on the thoughts about interval with respect to myocarditis 

and future plans Moderna has with respect to studying that.

Dr. Das indicated that they looked again at all of their studies and the interval is very tight. The 

checked whether it would be possible to tease out a 6-week interval, but the numbers are very 

small. They are using an 8-week interval in their infant study so it will better coincide with 

childhood immunizations. They have heard the feedback about studying at least the 

immunogenicity at the longer intervals and will take this back to find out what could be done 

from a clinical study immunogenicity standpoint in terms of the interval. Certainly, their animal 

studies show that the longer intervals are good for immunogenicity. 

EtR Framework: Moderna COVID-19 Vaccine in Children & Adolescents Ages 6-17 Years

Sara Oliver, MD, MPH (CDC/NCIRD) presented the EtR framework for the Moderna COVID-19 

vaccine in children and children 6−11 years of age and adolescents 12−17 years of age. The 

policy questions for this EtR Framework analysis were as follows:

 Should vaccination with Moderna COVID-19 vaccine (2-doses, 50 mcg, IM) be 

recommended for children ages 6–11 years, under an Emergency Use Authorization? 
ACIP Meeting Summary June 22-23, 2022

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 Should vaccination with Moderna COVID-19 vaccine (2-doses, 100 mcg, IM) be 

recommended for adolescents ages 12–17 years, under an Emergency Use Authorization?

In terms of the PICO question, the population is people ages 6−17 years of age with the 

comparison group of no vaccine. The outcomes of interest include symptomatic laboratory 

confirmed COVID-19, hospitalization due to COVID-19, MIS-C, SARS-CoV-2 seroconversion to 

a non-spike protein, asymptomatic SARS-CoV-2 infection, SAEs, reactogenicity Grade ≥3. 

While the analysis addressed individuals 6−17 years of age overall, the differences were 

highlighted in instances where there were data for children 6−11 years of age and adolescents 

12−17 years of age. 

Regarding the public health problem domain, there have been more than 85 million total 

reported cases of COVID-19 in the US as of mid-June 2020. Since April, there has been an 

increasing number of cases. This has been leveling out since late May, with a current 7-day

average of around 100,000 cases.99 In total during the pandemic, over 5.1 million cases have 

occurred among children ages 5−11 and more than 5.6 million cases have occurred among

adolescents ages 12−17 years.100 In April, unvaccinated individuals ages 5−17 years overall 

had a 2 times greater risk of testing positive for COVID-19 compared to children and 

adolescents vaccinated with at least a primary series.101 There has been an increase in 

hospitalizations among children and adolescents during the peak of the Omicron surge, leading 

to the highest hospitalization rates for these age groups to date during the pandemic.102 It is 

known that vaccination prevents hospitalization. Although children ages 5−11 years had lower

hospitalization rates overall than adolescents, the same pattern can be seen after they became 

eligible for vaccination in late 2021. It also is important to note that the benefits of vaccination 

are always more pronounced when the disease burden is high. It can be predicted that with 

future COVID-19 surges, the unvaccinated will continue to bear the burden of disease.103

To put the burden of COVID-19 illness in context, data from COVID-NET and FluSurv-NET, 

which conducts surveillance for influenza-associated hospitalizations from October 1st through 

April 30th of each year—the typical US influenza season. Among children ages 5−11 years,

COVID-19 hospitalization rates from October 2020 through September 2021 were lower than

influenza hospitalization rates during the 2017-2018 or 2019-2020 influenza seasons. However,

the preliminary hospitalization rates during the 2021 through April 2022 influenza season, which 

included the Omicron surge, were as high or higher than the influenza hospitalization rates for 

the prior included influenza seasons in this age group. However, the cumulative rates of COVID19 hospitalizations for both years are considerably higher than influenza hospitalization rates 

during all the prior influenza seasons among adolescents 12−17 years of age.104

99 Source: COVID Data Tracker, https://covid.cdc.gov/covid-data-tracker/#trends_dailytrendscases Accessed 6/21/2022 100 Source: COVID Data Tracker, https://covid.cdc.gov/covid-data-tracker/#demographicsovertime Accessed 6/16/2022 101 CDC COVID Data Tracker, https://covid.cdc.gov/covid-data-tracker/#rates-by-vaccine-status Accessed May 20, 2022 102 Source: COVID-NET, https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html Accessed 6/20/22 103 Source: CDC COVID Data Tracker: COVID-NET Hospitalizations by Vaccination Status. Accessed June 20, 2022 104 Delahoy MJ, Ujamaa D, Taylor CA, et al. Comparison of influenza and COVID-19-associated hospitalizations among children < 

18 years old in the United States-FluSurv-NET (October-April 2017-2021) and COVID-NET (October 2020-September 2021). Clin 

Infect Dis. 2022 May 20:ciac388. doi: 10.1093/cid/ciac388 
ACIP Meeting Summary June 22-23, 2022

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Moving to mortality associated with COVID-19 from January 2020 through May 2022, data from 

the National Center for Health Statistics (NCHS) showed that there were 189 COVID-19-related 

deaths among children 5−11 years of age. This represents 2.5% of all deaths in this age group.

There were 443 COVID-19 deaths among adolescents 12−17 years of age, which represents 

2.4% of all deaths in this age group.105 Approximately 36% of children ages 5−11 years of age 

and nearly 70% of adolescents have received at least 1 dose of COVID-19 vaccine through midJune. Overall, 18 million children ages 5−11 years and 7.5 million children ages 12−17 years 

remain unvaccinated.106

In summary of the available data for the public health problem domain, children and adolescents 

ages 5−17 years are at risk of severe illness from COVID. There have been over 10.3 million

cases reported in this age group and to date, sadly, over 600 deaths. Children and adolescents 

who have received COVID-19 vaccines have better outcomes than children who are

unvaccinated, particularly against severe illness. Approximately 65% of children 5−11 years of 

age and about 30% of adolescents have not yet received a COVID-19 vaccine. The WG 

determined that COVID-19 among children and adolescents is of public health importance.

Moving to benefits and harms domain, it is known that the timeframe during which studies were

conducted is critically important in the interpretation of efficacy results. The RCT, Study 203 for 

adolescents 12−17 years of age, was conducted during the original or ancestral strain and into 

the Alpha variant. The RCT, Study 204 for children 6−11 years of age, was conducted during

Delta.107 Neither of these studies was conducted during the Omicron surge, which is different 

than the VE results heard during the past weekend where the trials were conducted during 

Omicron.

First, to review the data for children 6−11 years of age. Overall, there are data from 1 study from 

the Moderna Phase 2/3 RCT. Participants were randomized 3:1 vaccine to saline placebo. Data

included all eligible randomized participants who received vaccination through the data cutoff of 

November 10, 2021. The available body of evidence is primarily from the Delta variant. The VE

estimates do not represent the most recent epidemiology. Per protocol, there were 2 co-primary

endpoints for efficacy based on immunobridging, GMRs and seroresponse. Data on

symptomatic COVID-19 using various definitions also were supplied. The 2-dose VE estimate 

was 75.8%. When those with prior infection are included, the CDC definition, VE is 80.6%.

Based on 8 total cases, each of these 2-dose estimates has a wide confidence interval. The 

immune response to vaccine was evaluated using the GMR of children to young adults. The 

non-inferiority criteria are met when the lower bound of the 95% confidence interval for the ratio 

comparing the geometric mean neutralizing antibody titers for the 2 groups is not less than a 

pre-specified value, which for this study was set at 0.67. The immune response to the vaccine in 

children 6−11 years of age was noninferior to that observed in those 18−25 years of age, with a 

ratio of 1.2 (1.1, 1.4). Therefore, the non-inferiority objective was met.

The GRADE assessment for symptomatic laboratory-confirmed COVID-19 using the direct

efficacy had serious concerns of imprecision due to the small number of events, with a final 

evidence type of Type 2 (moderate certainty). The GRADE evidence assessment for the

outcome of symptomatic laboratory-confirmed COVID-19 using immunobridging had serious 

concerns of indirectness, but immunogenicity is an indirect measure of efficacy. The final 

evidence type was Type 2 (moderate certainty). Next is the GRADE evidence for the outcome of

105 https://data.cdc.gov/NCHS/Provisional-COVID-19-Deaths-Counts-by-Age-in-Years/3apk-4u4f/data Accessed 5/14/22 106 CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#vaccination-demographics-trends Accessed June 20, 2022 107 Source: COVID Data Tracker, https://covid.cdc.gov/covid-data-tracker/#trends_dailytrendscases Accessed 6/16/2022 
ACIP Meeting Summary June 22-23, 2022

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asymptomatic SARS-CoV-2 infection. During the Phase 2/3 trials, participants were evaluated

for asymptomatic infection using a nasopharyngeal (NP) swab for reverse transcriptase

polymerase chain reaction (RT-PCR) testing on Day 57 or when unscheduled illness visits were 

triggered by a SARS-CoV-2 exposure. Participant with documented COVID-19 symptoms were 

excluded. There were 9 asymptomatic RT-PCR positives among over 2,600 vaccine recipients 

and 10 asymptomatic RT-PCR positive among 853 placebo recipients for an efficacy estimate of 

71% (28.8%, 88.1%). There was serious concern of indirectness because the full cohort was

only PCR tested on Day 57 and serology was not done for all participants. Therefore, the results 

do not represent full serologic testing. There also were serious concerns of imprecision due to 

the small number of events, so the final evidence type was Type 3 (low certainty).

Next is the outcome of SAEs. In the Phase 3 trial, 6 of approximately 3,000 participants in the 

vaccine group and participants out of almost 1,000 participants in the placebo group

experienced SAEs for a comparison of 0.20%. No SAEs were deemed related to the vaccine.

All participants who received at least 1 dose were included through the data cutoff of November 

10, 2021. For the GRADE assessment, there were serious concerns of indirectness due to the 

short duration of follow-up. There also were serious concerns of imprecision due to the width of

the confidence interval, which included estimates for which other policy options might be

considered. The final evidence type was Type 4 (very low certainty).

For the outcome of reactogenicity, reactions were solicited through electronic diaries for 7 days 

after each dose. The criteria for meeting Grade 3 or higher include local reactions of pain at 

injection site, redness, swelling, axillary swelling; and systemic events of fever, nausea/

vomiting, headache, fatigue, chills, new or worsened muscle pain, and/or new or worsened joint 

pain. Grade 3 local or systemic events were reported in 17% of persons in the vaccine arm and 

3% of those in the placebo arm. No Grade 4 events were observed in vaccine recipients. The 

GRADE assessment for this outcome with a relative risk of 5.2 (3.6, 7.3), there were no serious 

concerns in the certainty evidence estimate, so the final evidence type was Type 1 (high 

certainty).

To summarize the GRADE assessment for the Moderna vaccine in children 6−11 years of age 

in terms of benefits, the available data indicate that the vaccine was effective at preventing

symptomatic COVID-19 with direct efficacy and indirect immunobridging, both with an evidence 

of Type 2. Data also estimated the prevention of asymptomatic infection with less certainty and 

evidence of Type 3. In terms of harms, SAE reporting was comparable. Given that there was 

concern for indirectness and imprecision, the evidence was Type 4. SAEs were judged to be

related to the vaccine. Reactogenicity was more common in vaccinated persons, so the 

evidence was Type 1.

Moving to adolescents ages 12−17 years, participants were randomized 2:1 vaccination to 

saline placebo. Data included all eligible randomized participants who received vaccine through

the data cutoff of May 31, 2021. The available body of evidence was predominantly from a time 

period when either the original ancestral strain or the Alpha variant was the dominating

circulating variant. Therefore, these VE estimates do not represent the most recent

epidemiology. The data on symptomatic COVID-19 also was supplied using various definitions.

Per protocol, there were 2 co-primary endpoints for efficacy based on immunobridging, the

GMR, and seroconversion. Using the CDC definition, the VE estimate was approximately 89% 

based on 11 total cases. For the immunobridging assessment, the immune response to vaccine 

in those 12−17 years of age was non-inferior to that observed in those 18−25 years of age, with 

a GMR of 1.1 (0.9, 1.2). Therefore, the non-inferiority objective was met.
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For the GRADE assessment of symptomatic laboratory-confirmed COVID-19 using the direct

efficacy, there was serious concerns of imprecision due to the small number of events and the 

final evidence type was Type 2 (moderate certainty). For the GRADE assessment of 

aymptomatic laboratory-confirmed COVID-19 using immunobridging, there was serious concern

for indirectness because immunogenicity is an indirect measure of efficacy. The final evidence 

type was Type 2 (moderate certainty). For asymptomatic SARS-CoV-2 infection, asymptomatic

infection was measured in 2 ways with seroconversion from blood drawn on Day 57 and by NP 

swab for PCR at Day 57 if an unscheduled visit was triggered by SARS-CoV-2 exposure. There 

were 21 asymptomatic cases among around 2,000 vaccinated persons and 16 asymptomatic

cases among just over 1,000 placebo recipients for an efficacy estimate of 36.1% (-22.0%, 

66.5%), but the confidence interval was wide and included zero. For the GRADE assessment of

asymptomatic SARS-CoV-2 infections, there were serious concerns of imprecision due to wide 

confidence intervals and study size. The final evidence type was Type 3 (low certainty). 

For the outcome of SAEs, 6 out of approximately 2,400 participants experienced an SAE in the 

vaccine group and 2 participants out of approximately 1,200 experienced an SAE in the placebo 

group for a comparison of 0.16%. In terms of the GRADE assessment for this outcome, there

were serious concerns for indirectness due to short duration of follow-up and very serious

concerns for imprecision due to the wide confidence interval and study size. The final evidence 

type was Type 4 (very low certainty). For the outcome of reactogenicity in the Phase 3 study, 

local or systemic reactions were reported in about 25% of persons in the vaccine arm and about 

4.8% of persons in the placebo arm. The majority of these events were Grade 3. There were 3 

Grade 4 events in vaccine recipients, including 1 fever ≥40o C, 1 headache, and 1 nausea and 

vomiting. The GRADE assessment for reactogenicity had a relative risk of 5.2 (4.1, 6.8). There

were no serious concerns in the certainty assessment, so the final evidence type was Type 1 

(high certainty). 

To summarizes the GRADE assessment for Moderna COVID-19 vaccine in adolescents, as 

seen for children 6−11 years of age, the efficacy estimates for direct efficacy and

immunobridging were Type 2. SAE reporting was comparable, but there were concerns for

indirectness and serious concerns for imprecision, so the evidence type was Type 4. The 

evidence type for reactogenicity was Type 1. In conclusion, the efficacy seen after 2 doses of 

the Moderna COVID-19 vaccine in children 6−17 years of age is consistent with the real-world 

VE seen with SARS-CoV-2 variants at that time, which were Alpha or Delta depending on the 

age. Antibody levels after 2 doses in children and adolescents 6−17 years of age produced 

similar antibody levels after 2 doses in individuals aged 18−25 years. Reactogenicity after the 

vaccine is consistent with what has been seen in the Moderna vaccine in other age groups.

For the outcome of myocarditis considerations, from the safety presentation earlier from Dr. 

Shimabukuro showing the rates of myocarditis after mRNA vaccine, the rates were highest in 

males 12−29 years of age and after the second dose. Note that for those <18 years of age, the 

results were for only the Pfizer vaccine. Based on data presented to the ACIP in February 

2022,108 some but not all observational analyses of post-marketing data suggest that there may 

be an increased risk of myocarditis and pericarditis in males 18−39 years of age following the 

second dose of a Moderna vaccine relative to Pfizer vaccine. In summary of the findings from 

the data presented in February, the risk of myocarditis may be higher for Moderna than Pfizer, 

but there were important limitations to note, including that the data were observational, the rates 

were not readily comparable to differences in case definition and risk interval length,

108 Presented to ACIP Feb 4, 2022: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-02-04/11-COVID-Moulia508.pdf 
ACIP Meeting Summary June 22-23, 2022

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subpopulations, case ascertainment, calendar time, and implementation factors. In addition, a 

limited number of geographic locations were administering both mRNA vaccines and had data 

available on myocarditis. The ACIP also has heard data regarding the impact of extended 

intervals between Dose 1 and Dose 2 from Canadian colleagues showing that for both vaccine 

products, the overall myocarditis rates were higher when the interval between the doses was 

shorter, and myocarditis rates were lower with an extended interval between the two doses.109

To generally summarize myocarditis risk, the risk of myocarditis after the Modern vaccine is 

unknown in children and adolescents ages 6−11 and 12−17 years of age. Some observational 

data in adults suggest a possible increased risk after the Moderna vaccine compared to Pfizer. 

However, there is information on risk mitigation measure for myocarditis. Extending the interval 

between Dose 1 and Dose 2 of these mRNA COVID-19 vaccines to 8 weeks may further lower 

the myocarditis risk.

To summarize the known and potential benefits, the clinical trials provide data for protection

against symptomatic infection. The clinical trials were not powered to detect efficacy against 

severe disease, but similar patterns are expected to what those seen with mRNA COVID-19 

vaccines overall with higher protection against severe disease. As ACIP heard earlier in the day, 

emerging data in adults suggest that post-COVID-19 conditions may be less likely to occur in

vaccinated individuals. In summary of the known and potential harms, there are postauthoritarian safety data showing that after almost 600 million doses of COVID vaccines given 

in the US, the risk of adverse cardiac outcomes were 1.8−5.6 times higher after SARS-CoV-2 

infection than after mRNA COVID-19 vaccination among adolescent males 12−17 years of age. 

Importantly, there is a mitigation measure in that extending the interval between Dose 1 and 

Dose 2 of the mRNA vaccines to 8 weeks may further lower the myocarditis risk.

In summary of benefits and harms overall, the clinical trials were conducted prior to Omicron 

predominance. Post-authoritarian VE studies particularly against infection have shown lower VE

against Omicron compared to previous variants. However, the Moderna COVID-19 vaccine for 

older children and adolescents met the non-inferiority criteria for neutralizing antibody levels.

Receipt of a primary COVID-19 vaccine series can provide protection against both COVID-19 

disease and severe outcomes. Overall, the benefits of the Moderna vaccine in both children

and adolescents ages 6−17 years of age outweighs the risks and extending the interval

between Dose 1 and Dose 2 to 8t weeks may further optimize that benefit-risk balance by

lowering the myocarditis risk as well. The WG felt that the desirable anticipated effects are 

large, the undesirable effects are small, and the desirable effects outweigh the undesirable

effects in favor of the intervention.

Moving on to the values domain, adolescents 13−18 years and parents of adolescents 13−18 

years of age were surveyed using national research panels on 3 occasions or waves.110 Wave 1 

was before the COVID vaccine was available, Wave 2 was after vaccine was available for 

adults, and Wave 3 was after vaccine was available for persons ≥12 years of age. In terms of 

parent survey responses regarding the importance of both routine vaccines and COVID-19

vaccines, COVID-19 vaccines and influenza vaccines were rated similarly by parents. Overall, 

parents reported relatively high importance of getting the COVID-19 vaccines, although at times 

this was slightly less important than what was reported for other routinely recommended

109 Presented to ACIP Feb 4, 2022: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-02-04/09-COVID-Tunis508.pdf 110 Middleman, A. B., et al. (2022). "Vaccine Hesitancy in the Time of COVID-19: Attitudes and Intentions of Teens and Parents 

Regarding the COVID-19 Vaccine." Vaccines 10(1):4. https://doi.org/10.3390/vaccines10010004
ACIP Meeting Summary June 22-23, 2022

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vaccines. Regarding parents’ willingness to have their teen get the COVID-19 vaccine and other 

routine vaccines together, the CDC and AAP support giving other recommended childhood and 

adolescent immunizations at the same time as COVID-19 vaccinations, particularly for children

and teens who are behind on their routinely scheduled immunizations. When parents were 

asked for the willingness to have their teen get a COVID-19 vaccine and routine vaccine they 

may need at the same time, 70% were supportive. For those who selected “no” or “not sure,” 

further information was collected. The most common reason for not wanting this was that the 

teen was already up-to-date on recommended vaccines. However, some parents expressed 

concern regarding safety with concomitant administration.

Looking over time at parents’ willingness, 56% of parents said that their teen 12−17 years of 

age had been vaccinated, which has been fairly steady since January. About 3 in 10 parents 

said they would definitely not get their teen vaccinated. Over time, the “wait and see” population

has declined. The results were similar parents of children 5−11 years of age who have been

eligible for vaccinations since early November. About 4 in 10 of these parents said that their 

child has been vaccinated, 12% said that they will only get their child vaccinated if they are 

required to do so, and 32% said they definitely would not get their child vaccinated. While the 

“wait and see” population has declined in this age group over time as well, 10% to 13% of 

parents are still taking a “wait and see” approach.111 From the same survey that was conducted 

but this time in February, parents of adolescents expressed the most confidence in the safety of 

the vaccines for their children. Over half of parents of adolescents said that they were confident 

in the safety of vaccine, many of whom already had been vaccinated. Slightly fewer parents 

were confident in the safety of vaccine for children 5−11 years of age. Adolescents themselves 

were surveyed to gain a better perspective of potential factors that would increase their intent.

Potential factors among adolescents were more information on safety and efficacy, preventing 

the spread of COVID-19 to family and friends, and resumption of or increases in social activities 

or traveling.112

In summary of the values domain, over half of parents of adolescents 12−17 years of age and 

nearly 40% of children 5−11 years of age report that their child is already vaccinated or around 

30% of parents of both age groups report that their child definitely will not get vaccinated.

Parents of adolescents expressed the most confidence in safety whereas fewer parents of 

children 5−11 years of age are confident. Further information on the vaccine and resumption of 

social activities are important to adolescents. The WG felt that how the target population feels 

about the balance of desirable and undesirable effects varies. Not surprisingly, there was

important uncertainty or variability in how much people value the main outcomes.

Regarding the domain of acceptability, pediatricians and HCP are the top trusted source for 

information about the COVID-19 vaccines for children among parents across community types. 

While majorities or urban and suburban parents also trust their local health department or the 

CDC, rural parents are somewhat less trusting of these sources. Around half of parents across 

community types say their child’s school has provided them with information on how to get a 

COVID-19 vaccine for their child. However, smaller shares of rural parents say that their child’s 

school has encouraged them to get vaccinated compared to parents in urban areas. This

difference may play an important role in vaccine uptake for children across communities. As

previously reported, parents whose children’s schools encourage vaccination are more likely 

111 KFF COVID-19 Vaccine Monitor: February 2022. https://www.kff.org/coronavirus-covid-19/dashboard/kff-covid-19-vaccinemonitor-dashboard/#parents Accessed May 4, 2022 112 Scherer AM, Gedlinske AM, Parker AM, et al. Acceptability of Adolescent COVID-19 Vaccination Among Adolescents and 

Parents of Adolescents — United States, April 15–23, 2021. MMWR Morb Mortal Wkly Rep 2021;70:997–1003. DOI: 

http://dx.doi.org/10.15585/mmwr.mm7028e1 
ACIP Meeting Summary June 22-23, 2022

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than those whose school do not encourage vaccination to say their child had received a 

vaccine. Around half of all parents across community types say their child’s school provided

them with information around the COVID-19 vaccine. However, it is known that this varies by 

location.113

Jurisdictions have taken a broad approach to provide COVID-19 vaccines to children. Based on 

survey data among children and adolescents who received their COVID-19 vaccines,114 most

received their vaccine at either their medical home or pharmacy. This was even more important

among children 5−11 years of age. Schools and other mass vaccination sites were used less

frequently, especially for children 5−11 years of age. 

To summarize acceptability, most jurisdictions were utilizing a variety of implementation

strategies to vaccinate children and adolescents. However, it is known that most children in this 

age group are receiving their vaccine at either their medical home or a local pharmacy. 

Pediatricians or other HCP are the top source for information about COVID-19 vaccines for 

children among parents across community types. The WG felt that the Modern vaccine is 

acceptable to key stakeholders.

For the domain of feasibility,

115 the 50 mcg product for children 6−11 ships at -20°C. The 

product that will be used has the same cap color as the product for young children, but with a 

different border color. It has a different concentration than the adult primary series, although it 

has the same concentration as the product for young children. However, the vial authorized for 

this age group will be labeled as “Booster dose 18 years and over” authorized for use and it 

does not require diluent. The product for adolescents 12−17 years of age at 100 mcg has a red 

cap with a light blue border and is the same products and vial as used for adults. It is given at 

the 0.5 mL volume for primary series in individuals ≥12 years of age. Currently, the 0.25 mL 

volume is also being given for booster doses for those ≥18 years of age. There will not be a new 

national drug code (NDC) code for this as it is the same product for the primary series in those 

≥18 years of age that already is available. This product also does not require diluent. As 

additional vaccines and vaccines products continue to be rolled out, vaccines.gov is a way that 

parents and their children can find a COVID-19 vaccine.

To summarize the feasibility domain, the Moderna products for children and adolescents ages 

6−17 years of age may be less familiar to pediatric healthcare providers. However, they can be 

stored at a traditional freezer temperature and do not require diluent. The product for children

6−11 years of age will be labeled as a “booster dose for those 18 years and older,” which will 

require considerable education. The adolescent product is the same as the adult formulation

and will be more familiar to providers. The WG felt that the vaccine is feasible to implement, 

although challenges were noted with labels and the vials.

113 KFF COVID-19 Vaccine Monitor: Winter Update on Parents’ Views (November 8-23, 2021). https://www.kff.org/coronaviruscovid-19/poll-finding/kff-covid-19-vaccinemonitor-vaccine-attitudes-rural-suburban-urban/ Accessed March 7, 2022 114 National Immunization Survey Child COVID-19 Module (NIS-CCM) is an on-going random-digit-dialed telephone survey that 

began in July 2021 to collect COVID-19 vaccination status and intent for children from adult respondents knowledgeable about 

the child’s vaccination status. All estimates are weighted to represent the non-institutionalized U.S. population of children and 

mitigate possible bias that can result from an incomplete sample frame or non-response. Survey weights were calibrated to 

vaccine administration data reported to CDC. For more information about the survey, see https://www.cdc.gov/vaccines/imzmanagers/nis/about.html#nis-ccm and https://www.cdc.gov/vaccines/imz-managers/coverage/covidvaxview/index.html 115 CDC. Updated Pediatric COVID-19 Vaccination Operational Planning Guide – Information for the COVID-19 Vaccine for Children 

6 Months through 4 Years Old and/or COVID-19 Vaccine for Children 6 Months through 5 Years Old. 

https://www.cdc.gov/vaccines/covid-19/down
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102

For the domain of resource use, vaccines are currently available at no cost to recipients and 

that protection against severe disease is likely to result in a considerable reduction of healthcare 

cost. Cost-effectiveness is not the primary driver for decision-making during a pandemic, but will 

continue to be assessed. The WG felt that vaccines are a reasonable and efficient allocation of 

resources.

For the equity domain, vaccination coverage and parental intent suggest that for children 5−17

years of age, older children are more likely to be vaccinated than younger children and multiracial and Hispanic children are more likely to be vaccinated than Black or White children.116

Coverage among children 5−11 years of age varies by race and ethnicity, with nearly 72% of 

Black children 5−through 11 years of age remaining unvaccinated as of late April. Looking at 

coverage among adolescents 12−17 years of age with at least 1 COVID-19 vaccine dose by 

race and ethnicity shows that the unvaccinated population varies by race and ethnicity, with just 

over 40% of both Black and White adolescents who are unvaccinated. In terms of the percent of 

children and adolescents 5−17 years of age by Metropolitan Statistical Area (MSA), coverage is 

considerably lower among rural children.117 The potential drivers of this disparity are that rural 

parents reported less intent to vaccinate their children, there is lower vaccine safety confidence,

and more than half of rural parents stated that getting their children vaccinated against COVID19 would be a bigger risk for their children than the COVID-19 infection itself. 118

CDC has numerous communication resource materials available for vaccine providers and for 

partners, including vaccine pages focused on vaccinating children with disabilities, an updated 

quick conversation guide for talking with families, a Medscape commentary on routine pediatric 

and COVID-19 vaccination, customizable materials that align with key messages, and updated 

information for schools to include content for childcare partners.119 Culturally and linguistically

appropriate materials including printable fact sheets are available in a variety of languages

(Amharic, Arabic, Chinese, English, French, Korean, Portuguese, Spanish, Vietnamese).120

There also are focused resources to promote COVID-19 vaccine for children and teens with 

diverse images.121

In summary of the available evidence for the equity domain, there are noted disparities in

vaccination coverage and parental intent for children by age, race and ethnicity, and MSA. 

Communication materials that are culturally appropriate and diverse, including materials for 

children with special healthcare needs, are important. Overall, the WG felt that there potentially 

would be no impact for equity with the additional Moderna products. However, it is known that 

equity requires more of a call to action than a singular question.

116 CDC COVID Data Tracker. Trends in COVID-19 Vaccine Confidence in the US. https://covid.cdc.gov/covid-datatracker/#vaccine-confidence Accessed May 20, 2022 117 Source: Estimates produced by NORC at the University of Chicago using CDC’s National Immunization Survey-Adult COVID-19 

Module (NIS-ACM). COVID-19 Vaccination Coverage and Vaccine Confidence Among Children | CDC. Accessed May 25, 2022. 118 Source: Estimates produced by NORC at the University of Chicago using CDC’s National Immunization Survey-Adult COVID-19 

Module (NIS-ACM). COVID-19 Vaccination Coverage and Vaccine Confidence Among Children | CDC. Accessed June 2, 2022. 119 CDC. Vaccinating Children with Disabilities Against Disabilities. https://www.cdc.gov/vaccines/covid19/planning/children/disabilities.html Accessed June 21, 2022; CDC. Quick Conversation Guide on Pediatric COVID-19 

Vaccination. https://www.cdc.gov/vaccines/covid-19/downloads/talking-to-parents.pdf Accessed June 21, 2022 120 and additional resources: www.cdc.gov/vaccines/covid-19/planning/children/resources-promote.html 121 CDC. Vaccines and Immunizations. https://www.cdc.gov/vaccines/covid-9/planning/children/resources-promote.html Accessed 

June 21, 2022
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To summarize the WG’s interpretations for the EtR Framework domains, the WG discussed 

each age group for the Moderna COVID-19 vaccine primary series compared to no vaccine. As 

discussed during the ACIP meeting the previous week, 2 vaccine options may allow parents and 

providers a choice. The Moderna COVID-19 primary series in older children and adolescents 

met the non-inferiority endpoints, providing protection against symptomatic COVID-19 disease 

and are expected to provide higher protection against severe disease. The WG felt strongly that 

an interval of 6 weeks between Dose 1 and Dose 2 likely would improve safety and

effectiveness of the Moderna vaccine in older children and adolescents.

For the Moderna vaccine in children 6−11 years of age and adolescents 12−17 years of age, the 

WG found that the desirable consequences clearly outweighed the undesirable consequences 

in most settings. With this in mind, the WG proposed the following recommendations for 

separate ACIP votes:

 Moderna COVID-19 vaccine (2-doses, 50 μg, IM) is recommended for children ages 6–11 

years, under an Emergency Use Authorization.

 Moderna COVID-19 vaccine (2-doses, 100 μg, IM) is recommended for adolescents ages 

12–17 years, under an Emergency Use Authorization.

The WG discussed that an 8-week interval would increase the benefits and decrease the harms,

improving the balance of consequences for the 100 μg of Moderna in adolescents.

Clinical Considerations Update

Elisha Hall, PhD (CDC/NCIRD) presented updates to the Clinical Considerations. Beginning 

with a summary of the pediatric schedule for Moderna COVID-19 vaccine for ages 6−17 years, 

people who are not moderately or severely immunocompromised should receive 2 primary

doses separated by 4 to 8 weeks. People who are moderately or severely immunocompromised

should receive 3 primary doses each separated by 4 weeks. Like when other COVID-19

vaccines were first authorized for a specific age group, only primary doses are authorized at this 

time for people ages 6−17 years who receive the Moderna primary series. In terms of all of the 

recommendations for those who are not immunocompromised, depending on the age and 

product, people 6 months−17 years of age should receive either 2 or 3 doses. People who are 

moderately or severely immunocompromised, and depending on age and product, should 

receive between 3 and 5 total doses.

During the last ACIP meeting, there was discussion about considerations for an extended 8-

week interval between Dose 1 and Dose 2. Dr. Hall emphasized that the extended 8-week 

interval was particularly relevant to this meeting’s discussion in terms of the adolescent group. It 

may be more appropriate than the 4-week authorized interval in situations when the priority is to

reduce myocarditis risk. Some studies in adolescents and adults have shown that the small risk 

of myocarditis associated with mRNA COVID-19 vaccines might be reduced with this longer

interval. Use of this interval is especially important for adolescent and young adult males where 

higher risk has been observed, including among males 12−17 years of age. 
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104

Transitioning to the Moderna product for children and adolescents 6−17 years of age, the 

product authorized for children 6 months−5 years of age has a dark blue cap and magenta 

border label. A dose is 25 micrograms or 0.25 mL. The product authorized that will be available

for primary series doses for children 6−11 years of age also has a dark blue cap, but the label

border is purple. This product also is authorized for booster doses for adults ≥18 years of age. 

The label for this product reads “booster doses only” in all caps, but it is authorized for primary 

doses in children 6−11 years of age. For both children 6−11 years of age and adults ≥18 years

of age, the dose is 50 micrograms or 0.5 mL. Like all Moderna COVID-19 vaccine products, it 

should not be diluted and there are 5 doses per vial. Another product is authorized for children 

6−11 years of age with a dark blue cap and teal border label. Given that it is not available, Dr. 

Hall did not into detail on that product and discussed only the product with the dark blue cap, 

purple border label for ages 6−11 years, and “booster doses only” in all caps.

The Moderna product with the dark blue cap, purple border label for ages 6−11 years, and 

“booster doses only” in all caps is authorized for primary doses in children 6−11 years of age 

and booster doses in adults ages 18 years of and older. It also states on the label “2.5 mL MultiDose Vial Booster Dose 0.5 mL.” However, 0.5 mL is the correct dose volume for both the

booster dose and primary doses for children 6−11 years of age. The currently available product 

for ages 18 years and older has been amended to include ages 12 years and older. It has a red 

cap and a light blue label. A primary series dose will continue to be 100 mcg or 0.5 mL for 

adolescents 12−17 years of age. The booster dose is authorized only for persons for 18 years of 

age and older. Adolescents 12−17 years of age can receive only the primary series dose at this 

time.

CDC recognizes that that label for children 6−11 years of age stating “booster doses” in all caps 

is very confusing. There will be multiple education and communication materials and efforts to 

communicate the authorized use of this vial for ages 6−11 years. A wall chart is available from 

the FDA with color photographs of the Moderna COVID-19 vaccine presentations.122

Additionally, the EUA for ages 6−11 includes the picture of the booster-only vial of both the label 

and the vial to show what providers would actually see in their stock.123 CDC also will have 

multiple products and communication efforts to communicate the use of the vial. The Clinical 

Considerations124 will be updated and will have information on the different products. CDC has a 

multiple product-specific job aids, including an at-a-glance job aid and prep and administration 

summary.125 Additionally, CDC will be educating through webinars, calls, and partners to help 

providers with this confusing label situation.

As discussed during the last ACIP meeting, children should receive the age-appropriate vaccine

product and follow the schedule based on their age on the day of vaccination regardless of their 

size or weight. If a person moves from a younger to an older age group during the primary

series or between the primary series and receipt of a booster dose, they should receive the

vaccine doses for the older age group for all subsequent doses. The booster does not apply to 

this particular product and age group combination. Even though CDC recommends using the 

product based on age on the day of vaccination, there are some different FDA allowances for 

aging up. Children who age from 5 to 6 years between any does in the primary series may

122 Wall chart: https://www.fda.gov/media/159306/download 123 Fact Sheet for Healthcare Providers: 6 Through 11 Years: https://www.fda.gov/media/159308/download; and 12 Years and 

Older: https://www.fda.gov/media/157233/download 124 Clinical considerations: https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us.html 125 Job aids: https://www.cdc.gov/vaccines/covid-19/info-by-product/moderna/index.html 
ACIP Meeting Summary June 22-23, 2022

105

receive either the Moderna product authorized for children 6 months−5 years of age (dark blue 

cap, magenta label border) and the Modern product authorized for children 6−11 years of age 

(dark blue cap, the purple border) for Dose 1 and at 4 to 8 weeks later, the product with 

magenta or purple border can be used. Children who turn from age 11 to 12 years between any 

dose in the primary series may receive either the Moderna product authorized for children ages 

6−11 years of age or the Moderna product authorized for children ages 12−17 years of age. For 

Dose 1, this would be the dark blue cap with the purple border or the red cap with the light blue 

border. For Dose 2 at 4 to 8 weeks later, either vial is acceptable.

In terms of administration, the existing guidance applies to children and adolescents 6−17 years

of age. COVID-19 vaccines may be administered without regard to timing of other vaccines. 

COVID-19 vaccines are not interchangeable. The same products should be used for all doses of

the primary series. With all of these new products and products not labeled for the indicated age 

group, there may be more opportunities for vaccine administration errors. Additionally, new 

pediatric providers may be unfamiliar with COVID-19 vaccines. There are some stark

differences between routine vaccines. Some of the most likely errors to look out for within this

context would be incorrect product and/or dose volume, resulting in a higher than authorized 

dose; incorrect product and/or dose volume resulting in a lower than authorized dose; a correct 

dose from an incorrect product; and/or vaccine administered beyond use date. There are a 

number of resources available for preventing administration efforts.126

Discussion Summary (Oliver & Hall)

Dr. Lee said that as someone who cares about implementation, she wanted to ask their 

manufacturer colleagues to make it easier for providers to do the right thing. She was looking at 

teal, magenta, maroon, orange, red, lots of blue, and sometimes with the same color cap and 

sometimes with a different color caps. Now there are labels that differ from how the products are 

actually supposed to be used. She expressed appreciation to the CDC for putting together the

types of training and support that will be needed to implement this product. She also recognized 

that this will impact acceptability from a provider standpoint because there is a lot of complexity

to incorporate into the busy practice. She asked Pfizer and Moderna whether they have any

plans to improve the design and labeling of these vials, because this is quite overwhelming her 

even though she feels like she knows COVID-19 pretty well.

Dr. Das said that Moderna definitely hears the feedback, which has arisen at the speed with 

which these have come forward. They are actively working on how to simplify this.

Dr. Poehling emphasized concern about the confusion on the labels for both doses and 

highlighted that there are people who are color blind, which she worries will contribute to errors. 

She pointed out that the vast majority of vaccines for children 5−11 and 12−17 years of age will 

be given in the medical home. She requested additional information about persons who do and 

do not have immunocompromising conditions in terms of the booster dose recommendation, 

though it was not part of the upcoming vote.

126 Web-on-demand “mini” webinar: https://www2.cdc.gov/vaccines/ed/covid19/videos/va/va.asp; Vaccine Administration: Preventing 

Vaccine Administration Errors https://www.cdc.gov/vaccines/hcp/admin/downloads/vaccine-administration-preventing-errors.pdf; 

and Vaccine storage, handling, preparation, and administration materials: https://www.cdc.gov/vaccines/covid-19/info-byproduct/moderna/index.html
ACIP Meeting Summary June 22-23, 2022

106

Dr. Hall indicated that this is another difficult communication point. For Moderna, there is no 

current booster recommendation for persons 6 months−17 years of age because the FDA has 

authorized only the primary doses at this time and has not yet authorized a booster dose. It is 

assumed that by the time this age group who receive Moderna would be eligible for a booster,

there probably would be a booster dose authorized because there would be more data at that 

point. For the Pfizer product, 1 or 2 booster doses are authorized for children and adolescents 

5−17 years of age depending on the exact age and immune compromise. The at-a-glance 

schedule should be more helpful as well.

Dr. Fink indicated that FDA would expect to be addressing this gap in booster dose

recommendations over the Summer and into early Fall.

Ms. Bahta requested clarification from Dr. Hall about children needing a dose based on the age 

of the day they were vaccinated, given that she went on to explain that there are exceptions 

related to the Moderna vaccine for children in the transition age being able to get either dose. 

This seems complicated and confusing.

Dr. Hall used the example of aging from 5 to 6 years. The CDC recommendation would be to 

use the product based on the age the day of vaccination. A child 5 years of age in the provider’s 

office would be vaccinated with the product for children 6 months−5 years of age. Within the 4 to 

8 weeks before the second dose, they age up to 6 years and present to the provider’s office for 

the second dose. On that day, they can be vaccinated with the product authorized for children 

6−11 years of age. However, the FDA authoritarian allows for either of those products to be 

administered for either the first or the second dose. This allows for more flexibility. CDC is 

working on a visual for this because this is a very confusing concept.

Dr. Sanchez agreed that this is extremely confusing, and consistency is needed. He joined in 

urging the manufacturers to work on this to minimize any errors and to improve safety. In 

addition to color, there should be information about micrograms.

Dr. Fryhofer (AMA) said that speaking as a practicing physician, she echoed some of the

concerns about the colorful caps and labels being complex and confusing. She was shocked 

that the concentration was not listed on the label. The concentration should be on the bottles as 

a final check before these doses are administered.

Dr. Rita Das indicated that the concentration is the only thing that is different. The product is the 

same.

Dr. Hogue (APhA) pointed out that pharmacists are very focused on ACIP recommendations

and CDC’s Clinical Guidelines for the use of vaccines. It has not been unusual in the past to 

have had vaccine products that contain an FDA label that is for a different age range than CDC 

recommends. The APhA has been strong about promoting to pharmacists that they always 

should follow CDC’s Clinical Guidelines. He thought that was true for his colleagues in nursing 

as well. He also inquired as to when the teal-colored label for the Moderna product that is not 

yet available and would be at the appropriate dosage for children 6-11 years of age is likely to 

be available in the US so that providers do not have to deal with these extraordinary mislabeled 

products.

Dr. Das indicated that Moderna is actively assessing this, but does not have a definitive timeline 

at this point.
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107

Dr. Lee pointed out that this is a slightly unique situation with EUAs in terms of provider 

agreements and in which there are CDC recommendations, but the FDA has written 

allowances. She emphasized that the CDC recommendation is to the appropriate dose for the 

age on the day of presentation for the vaccine. It seems purposeful to have included the 

allowances so that people can have the assurance that that is not considered an error and that 

there is some flexibility.

Dr. Daley extended gratitude to Dr. Fink and his team for his leadership and for their reviews, 

emphasizing that it was not an overstatement to say that they were asked to do a year’s worth

of work in several weeks and they had done so without skipping any steps. It also was not an 

overstatement to say that Dr. Oliver and her team was asked to complete a year’s worth of work 

in several weeks without skipping steps and in bringing all of these data to ACIP. It struck him 

that simplification was going to require collaboration between manufacturers, the FDA, and the 

CDC to avoid vaccine administration errors. For other vaccines, there is the concept about 

minimum and recommended intervals and accelerated schedules. If more data become 

available about the benefits of 8 weeks between a first and second dose of an mRNA vaccine, it 

was his understanding that some regulatory steps would need to be taken. He requested 

additional information about this.

Dr. Oliver emphasized that the votes during this session would be for the authorized schedule in 

terms of doses and intervals. This is a unique situation in terms of EUAs, legal ramifications, 

and everything that is tied to that. However, the 8-week interval is included in the Interim Clinical 

Considerations. This will continue to be stressed in terms of education and the schedule. The 

hope is that over time, there will be a less constrained environment.

Dr. Fink agreed that it has been challenging to navigate the various legal considerations around 

EUAs and provider agreements in terms of trying to address various clinical scenarios.

Considering whether and how to update FDA labeling to include a different interval is tied

together with an EUA having to be reflected in the approved labeling. The situation is somewhat 

paradoxical in that the level of evidence that typically would be required to support a revision to 

labeling of a BLA product is higher than what might be necessary to support a change to an

EUA. Ultimately, FDA would have to work with the manufacturers to consider available data and

whether those data would meet FDA’s evidentiary standard for a labeling change. He thought 

they could do this at the BLA stage, but then there is the paradox at the BLA stage when there

is probably more flexibility in what ACIP is able to do with regard to off-label recommendations.

Dr. O'Leary (AAP) said that speaking as a colorblind person himself, the colors are a nightmare.

It would simplify the lives of those stocking vaccines to simply have 1 product rather than having

to stock 2 different products for the 2 different age groups. The doses essentially would be the 

same for children 6−11 years of age. This potentially could decrease administration errors and

simplify stocking from the standpoint of general pediatricians, family doctors, pharmacists, et

cetera.

Dr. Sanchez emphasized that dosing needs to be clarified with respect to Moderna dosing

and immunocompromised individuals. He remains concerned that there may be a switch over to 

Pfizer to provide further doses. Timely guidance is needed on further dosing of the Moderna 

vaccine in immunocompromised children.
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Dr. Oliver clarified that for the Moderna product for persons 6 months−17 years of age, there will 

be a third dose in the primary series as a part of the CDC recommendations. Boosters are not 

yet approved by FDA, but that may change over time. It is a 3-dose primary series for children 

who are immunocompromised. If the vote results in a CDC recommendation, the extra dose of 

Moderna for immunocompromised children will be take care of. 

Votes: Moderna COVID-19 Vaccine in Children & Adolescents Ages 6-17 Years 

Sara Oliver, MD, MPH (CDC/NCIRD) reminded everyone that since the beginning of the 

COVID-19 pandemic, there have been over 10 million COVID-19 cases, over 45,000 

hospitalizations, and tragically over 600 deaths among children ages 5 through 17 years of age. 

COVID-19 can cause severe disease and death among children and adolescents, including

those without underlying medical conditions. Future surges will continue to impact children, with 

unvaccinated children remaining at higher risk of these severe outcomes. As with all other age

groups, the priority is vaccination of unvaccinated individuals. Currently, there are 25 million 

unvaccinated children and adolescents. The benefits are known to outweigh the risks for mRNA 

COVID-19 vaccine in all ages. Receipt of this primary series continues to be the safest way to

prevent serious COVID-19. She then presented the following proposed recommendations, each 

of which was to be voted on separately:

Vote #1

“A two-dose Moderna COVID-19 vaccine series (50 μg) is recommended for children 

ages 6–11 years, under the EUA issued by FDA.”

Vote #2

“A two-dose Moderna COVID-19 vaccine series (100 μg) is recommended for 

adolescents ages 12–17 years, under an EUA issued by FDA.”

Discussion Summary

Dr. Long acknowledged that Moderna vaccine compared with Pfizer was not studied head-tohead to be able to say the intervention favors both and she understood why. However, the fact 

is that the Pfizer vaccine is currently recommendation in these age groups. There have been 

many presentations and she thought the world would expect ACIP to weigh in on whether the 

possible increase in myocarditis dissuades them from considering these vaccines differently.

She thought they needed to state somewhere that this offers the option and there is not a 

preference. It is an unusual situation to have had a research vaccine approved during the

research for this vaccine, so there is a standard. They would not let anybody use a placebo any 

longer. 

Dr. Lee said that while she understood the recognition that there is no preference and she also 

thought it should go into a statement, it would be her preference not to get into a pattern of 

incorporating that into every single vote with multiple vaccine products.

Dr. Wharton added that there were several votes the previous day in which the committee 

recommended products as acceptable alternatives to already recommended products. This 

discussion seemed analogous to what the committee did the previous day.

Dr. Sanchez asked whether anything needed to be said in the vote language about the 3-dose 

series for children who are immunocompromised or if it would just appear in the Clinical 

Considerations.
ACIP Meeting Summary June 22-23, 2022

109

Dr. Oliver clarified that the 3-dose series for children who are immunocompromised would not 

be included in the vote language, but will be taken care of within the official CDC 

recommendation. ACIP voted previously and broadly for the additional dose in 

immunocompromised children, which would stand as ACIP’s endorsement. 

Motion/Vote #1: Moderna COVID-19 Vaccine in Children & Adolescents Ages 6-11 Years

Dr. Poehling made a motion for ACIP to adopt the recommendation stating that, “A two-dose 

Moderna COVID-19 vaccine series (50 μg) is recommended for children ages 6–11 years, 

under the EUA issued by FDA.” Ms. Bahta seconded the motion. No COIs were declared. The 

motion carried with 15 affirmative votes, 0 negative votes, and 0 abstentions. The disposition of 

the vote was as follows:

15 Favored: Ault, Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long,

McNally, Poehling, Sanchez, Talbot 

 0 Opposed: N/A

 0 Abstained: N/A

 0 Absent: N/A

Motion/Vote #2: Moderna COVID-19 Vaccine in Children & Adolescents Ages 12-17 Years

Dr. Kottong made a motion for ACIP to adopt the recommendation stating that, “A two-dose 

Moderna COVID-19 vaccine series (100 μg) is recommended for adolescents ages 12–17 

years, under an EUA issued by FDA.” Dr. Sanchez seconded the motion. No COIs were 

declared. The motion carried with 15 affirmative votes, 0 negative votes, and 0 abstentions. The

disposition of the vote was as follows:

15 Favored: Ault, Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long,

McNally, Poehling, Sanchez, Talbot 

0 Opposed: N/A

0 Abstained: N/A

0 Absent: N/A

RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINES 

Session Introduction

Camille Kotton, MD (Chair, Adult RSV WG) introduced ACIP’s Adult Respiratory Syncytial 

Virus (RSV) WG. This WG will complement the one chaired by Dr. Sarah Long that focuses on 

RSV disease in infants and children. During this session, these 2 WGs jointly presented 

information on the epidemiology of RSV across the lifespan. Dr. Kotton shared the current 

membership roster and noted that the Adult RSV WG may still welcome liaisons from additional 

professional organizations, such as the Infectious Disease Society of America (IDSA), the 

National Foundation for Infectious Disease (NFID), et cetera. She highlighted that one of the 
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WG’s consultants, Marie Griffin (Vanderbilt University Medical Center), recently had a nice 

editorial published in the in the New England Journal of Medicine (NEJM) about RSV vaccines.

In terms of the purpose of the Adult RSV WG, RSV is a major cause of lower respiratory illness, 

particularly among infants and children and among older adults and adults with chronic medical 

conditions. RSV vaccine and immune-prophylaxis development has progressed in the past 

decade, with over 40 candidate vaccines and monoclonal antibodies currently in development. 

Target populations for whom these products are intended include infants and young children, 

pregnant women, and older adults. This WG will consider policy questions related to adult 

vaccination.

The WG activities include considering recommendations for use of RSV vaccines in adults by: 

1) reviewing the epidemiology and burden of RSV disease in older adults; 2) reviewing the 

efficacy, immunogenicity safety, and cost-effectiveness of these vaccine in older adults; 3) 

providing evidence-based recommendations regarding routine use of RSV vaccines in older 

adults; and 4) identifying areas in need of further research for informing potential future vaccine 

recommendations, including risk-based indications for adults with underlying medical conditions 

younger than the age for routine immunization recommendation.

There are 5 adult RSV vaccine products expected to be reviewed by the WG in the near future. 

GSK started its pivotal Phase 3 trial in May 2021. They have developed a protein-based vaccine 

adjuvanted with their proprietary compound, which also is used in Shingrix and other GSK 

vaccines. Pfizer started a Phase 3 trial in September 2021. They have a protein-based vaccine 

with no adjuvant. Janssen also started its pivotal Phase 3 trial in September 2021. They have 

an adenovirus vector, the same as used in the COVID-19 vaccine made by them, combined 

with a soluble protein. Moderna started its Phase 3 trial in February 2022. They have an mRNA 

vaccine. Bavarian Nordic started their Phase 3 trial in April 2022. They have a vaccinia vector, 

including multiple RSV vaccine antigens.

In terms of the tentative timeline, this ACIP session focused on the epidemiology and burden of 

RSV disease. During the October 2022 ACIP meeting, the WG will have 1 to 2 manufacturer 

presentations and GRADE reviews for 1 to 2 vaccine products. During the February and June 

2023 ACIP meetings, there will be more manufacturer presentations, GRADE reviews, costeffectiveness reviews, EtR Framework presentations for 1 to 2 vaccine products, and 

presentation of policy options over time as there may be an effective vaccine on the market for 

the season in later 2023.

RSV Virion and Vaccine Products

Natalie J. Thornburg, PhD (CDC/NCIRD) provided background about the virus and the 

vaccines that currently are in pre-clinical and clinical trials. RSV is a filamentous virus that is 

part of the orthopneumovirus family. It has a 15.2-kilobase (kbp) pair genome. It has a singlestranded negative sense RNA genome that encodes 11 proteins. It can be broadly divided into

two subgroups or serotypes, A viruses and B viruses. RSV A viruses and B viruses are known

to co-circulate within communities at the same time. The RSV virion has an envelope and 2 

major proteins, Attachment (G) or glycoprotein and Fusion (F) protein. Both of these proteins 

can be targets for neutralizing antibodies. There are products in pre-clinical and clinical trials

that target F alone, some that contain both F and G, and some that contain other antigens as 

well.
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F and G are both targets of neutralizing antibodies. It is known through absorption assays that 

most of the neutralizing activity is directed against the F protein, but not all. The G protein is

what defines RSV A versus RSV B. It is used because it has a heterogeneous sequence. It has 

2 large mucin-like domains, which provide antigen masking. RSV G establishes the A and B 

viruses because it is the most variable in the genome, while F is more conserved. This figure127

from a paper in the Journal of Virology of a map of the variability in the first half of the genome. 

This map lacks the second half of the genome, which encodes just 1 protein, the L polymerase, 

which is fairly conserved and not a target for neutralizing antibodies. Across the top of this map, 

gene products are listed, with the percent variability within an entire gene between A and B 

viruses shown in parenthesis. The percent variability across the entire gene within B viruses is 

listed in the top in red. The substitution per site of each amino acid is shown in the graph, with 

RSV A viruses being in black and RSV B viruses being in red:

Specifically paying attention to the G gene and the F gene, or G protein and F proteins,

because those are the targets of neutralizing antibodies, the number of substitutions per site of 

RSV A is higher and RSV B, in red, is higher in each residue. Across the whole gene in G, there 

is about 53% difference between A and B viruses in gene and across F there is only a 15%

difference between A and B viruses in F. For context, like in H1 versus H3, hemagglutinin is 

about 60% divergent. An Omicron spike versus an ancestral spike has about 3% amino acid 

changes. Not as much divergence is being seen in RSV viruses between A and B, but it is 

somewhat more in Omicron versus ancestral strain. Though the Omicron mutations were more 

concentrated in the receptor-binding domain, which may have contributed to partial escape.

F may not have much sequence diversity, but it has a lot of structural diversity and it exists in at 

least 2 or more structural forms that present very differently to the immune system. This 

figure128 is 2 crystal structures of the same protein with the same sequence. The left is a semistable prefusion form of the RSV F protein and the right is a more stable postfusion RSV F 

protein:

127 Lydia Tan et al. J. Virol. 2013;87:8213-8226 128 Graham B. Current Opinion in Virology. 23: 107-112. 2017
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Different anagenic regions or epitopes are colored on the surface. Some sites are present in the

prefusion stable site that are not accessible in the postfusion site. Antibodies that bind these

antigenic regions can have different potencies. It is known that antibodies against Site 0 (red) 

and Site 5 (orange) are more potent. Site 1 (blue) tends to be less potent. As noted earlier, the 

most potently neutralizing antibodies are directed against F. In these same studies, preabsorption of sera with prefusion F removes almost all neutralizing activity, consistent with the 

idea that Site 0 and Site 5 have the most potently neutralizing antibodies directed against them.

There are at least 5 general categories of RSV preventatives in clinical trials. There are 4 

vaccine products: 1) live attenuated and chimeric vaccines, which would contain many antigens; 

2) protein-based, which can be subdivided into at least 3 different kinds of protein-based 

vaccines (e.g., inactivated, whole virus particle-based vaccines, or subunit traditional protein 

vaccines); 3) nucleic acid vaccine products; and 4) recombinant vectors such as the Bavarian 

Nordic product. The fifth category in clinical trials are immunoprophylaxis products. There is one 

already being used for pediatric cases, Synagis® or palivizumab, and there are multiple new

monoclonal antibody immunoprophylaxis products in pre-clinical and clinical trials. PATH 

maintains an RSV vaccine and monoclonal antibody snapshot that tracks the various products 

that are in preclinical and clinical trials and is updated this frequently.129 And you can see on the 

bottom left when this was most recently updated.

The variability in G and across F is somewhat more complicated in F. While there is not a lot of 

variability in F, there is structural variability. Some sequence variability is observed in RSV F. All 

products target F or contain F. F sequence variability in circulating viruses will affect different

types of products’ difference. A manuscript published by Piedra and Hause from Baylor130

looked at amino acid variability for more than 1,000 sequences from RSV A and RSV B viruses

collected between 1961 and 2014. This was mapped on top of the anagenic regions and they 

found that there was more variation in RSV B viruses in the fusion protein. There are regions

where there is quite a lot of variation and regions where there is not so much variation. The RSV 

A regions that encode Site 0 are generally fairly conserved, but there is some mutation in RSV

B viruses in Site 0.

129 https://path.org/resources/rsv-vaccine-and-mab-snapshot/ 130 Hause et al. Plos One. 0175792. 2017
ACIP Meeting Summary June 22-23, 2022

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In summary of the virus and vaccine products, F and G are on the surface of the virus and are 

targets for neutralizing antibodies, with the most potent antibodies directed against the F 

protein. Some RSV trial vaccine products have just the F protein or a combination of F and 

other RSV antigens. Immunoprophylactics are directed against the F protein. There is some

heterogeneity in the RSV F protein, which could affect monoclonal antibody prophylaxis or 

potentially vaccines.

Discussion Summary

Dr. Poehling asked whether the outcomes have been synchronized across these studies as was 

done with COVID-19 vaccines.

Dr. McMorrow confirmed that the majority of the trials look at medically attended lower

respiratory tract infection (LRTI) as a primary outcome and RSV-associated hospitalizations as 

a secondary outcome.

Dr. Long asked whether Dr. Thornburg could speculate on the fact there are multiple RSV

infections, even in the same season, so that it is not predominantly related to mutation and

escape but rather some variances of the mucosal immune response that is very short-lived. 

Dr. Thornburg agreed with that hypothesis. Within a season, there does not tend to be a lot of 

virus drift. RSV is well known not to establish good immunological memory, RSV infections, and 

particularly not good mucosal immunological memory.

Based on the data shown, Dr. Lee asked whether Dr. Thornburg would hypothesize that

nirsevimab would potentially be more protective in a way than palivizumab has been. 

Dr. Thornburg said she thought that the IC50 value of nirsevimab is that is known to be higher

than palivizumab. Whether having more potent neutralizing activity means that it is more

effective will be for the trials to determine.

Dr. Lee asked when infection becomes established in an individual who might have received 

monoclonal antibody whether more of a prefusion or postfusion state is anticipated, with the 

assumption that the prefusion state would be ideal.

Dr. Thornburg indicated that the prefusion state is most likely what it looks like on a viral particle 

when someone is infected. It is hypothesized that it is triggered to the postfusion state after it

enters a cell. The hypothesis is that the immune system is seeing the fusion protein in a state 

that looks more like prefusion than postfusion.

RSV Seasonality in the US and the Burden of RSV in Children

Meredith McMorrow, MD, MPH, FAAP (CDC/NCIRD) provided a brief introduction to RSV 

seasonality in the US and the burden of RSV in children. The CDC’s National Respiratory and 

Enteric Virus Surveillance System (NREVSS) is its primary source for monitoring RSV

seasonality in the US. The NREVSS is a passive, laboratory-based surveillance system that

includes commercial, hospital, and state and local public health laboratories. Approximately 300 

laboratories routinely report RSV results. They provide weekly reporting of the total tests

performed for RSV and RSV-positive tests to monitor real-time virus circulation. All test types 
ACIP Meeting Summary June 22-23, 2022

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are reported. In recent years, the majority of tests are PCR assays. Testing is primarily cliniciandirected and includes persons of all ages.

Looking at normalized RSV detections by epidemiologic week from NREVSS during 

2011−2020, RSV circulation was highly seasonal in the US, with predictable peak activity during 

December to February annually. Using NREVSS data (excluding Alaska, Florida, and Hawaii) 

CDC assessed geographic differences in RSV seasonality in the US in the 3 seasons preceding 

the COVID-19 pandemic. A threshold of a 10-fold increase over baseline was applied to

calculate median seasonal onset, peak, and end weeks over 3 seasons from July 2017 through 

June 2020. Using this method, the onset of the RSV season in the US overall and in the

Northeast and Midwest Census regions was in late October. Typical onset was approximately 1

week earlier in the South region and approximately 2 weeks later in the West region. Seasonal

peaks and offsets also were earlier in the South and later in the West. RSV seasonality also 

was compared from NREVSS to pediatric hospitalizations in children <2 years of age from 7 

pediatric medical centers across the US that from the New Vaccine Surveillance Network

(NSVN). The onset of RSV-associated hospitalizations in NVSN was 1 week after the US onset

peaked in mid-December and ended 2 to 3 weeks earlier than the US average.

The seasonality of RSV may be different in Florida, Hawaii, and Alaska where seasons may 

start earlier, later, or maybe longer than the US average. Although there are slight differences in 

onset, peak, and offset across US Census regions, peak RSV transmission in the US and all 

regions occurs on average during December to February. More than 90% of RSV detections 

reported in NREVSS occurred during the 4 pre-pandemic seasons occurred between November 

1st and March 31st. The COVID-19 pandemic interrupted seasonal circulation of RSV and many 

other respiratory viruses. Following over a year of limited RSV circulation, the US experienced 

an inter-seasonal RSV that peaked in early August 2021. That peak continued through the Fall 

into late December. Although nationally RSV circulation has remained near the inter-seasonal 

baseline, increased RSV circulation is currently being seen in HHS regions 4 and 6. These 

increases may be limited or may herald another atypical RSV season. However, it is anticipated

that RSV circulation eventually will return to typical winter seasonality.

In terms of burden in children, RSV infection is the leading cause of hospitalization in US

infants. Most infants are infected in the first year of life and nearly all by 2 years of age.131

Approximately 40% of infected infants will develop a LRTI called bronchiolitis, among whom 3%

to 5% will require hospitalization. Premature infants born at less than 30 weeks gestation have 

hospitalization rates 3 times higher than term infants.132 Preterm infants also have higher rates 

of intensive care unit (ICU) admission and mechanical ventilation than term infants. The 

average cost of hospitalization in infants less than 29 weeks gestation is about 4 times higher

than for a term infant.133 Although prematurity is an important risk factor for hospitalization, RSV 

also is the leading cause of hospitalization in healthy term infants. An estimated 79% of children 

hospitalized with RSV age less than 2 years had no underlying medical conditions.134 In short, 

all young infants are at risk of severe RSV and 2% to 3% of all infants will be hospitalized for 

RSV in the first year of life.135

131 Glezen et al, Arch Dis Child, 1986 132 Hall et al, Pediatrics, 2013 133 McLaurin et al, J Perinatol, 2016 134 Hall et al, Pediatrics, 2013 135 Hall et al, Pediatrics, 2013 and Langley & Anderson, PIDJ, 2011
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It is estimated that each year in the US among children less than 5 years of age, RSV is

associated with 100 to 300 deaths;136 58,000 to 80,000 hospitalizations;137 520,000 ED visits;

138

and approximately 1.5 million outpatient visits.139 Estimates of RSV-associated hospitalization 

rates vary by year, study design, and assumptions. An industry-sponsored systematic review 

published earlier this year estimated a median annual rate of 25.6 per 1000 infants age 0−5 

months across 25 studies.140 This rate included 4 cities with a single year of hospital data and 5 

studies with 2 years of data. Rates were imputed, not directly reported, from all but 9 studies.

Median estimates varied considerably based upon methods, with the lowest estimates (15.8)

derived from active surveillance and the highest (31.2) from modeling studies. Clear outliers 

were not excluded from calculations. For cost-effectiveness analyses, CDC will use estimates

from active surveillance in primary analyses and other estimates will inform sensitivity analyses.

CDC generates RSV-associated disease burden estimates from the NVSN. NVSN conducted 

year-around acute respiratory illness surveillance at 3 sites during 2000-2009 and expanded to 

7 sites during 2016-2021. These same 7 sites have continued prospective surveillance in

inpatient, ED, and outpatient clinics. Following enrollment, respiratory samples are collected and 

undergo PCR testing for multiple respiratory viruses, including RSV. Population denominators

and market share are used to estimate disease burden, including hospitalization rates per 

100,000 population. NVSN data have consistently demonstrated in 2 4-year surveillance periods

that RSV-associated hospitalization rates are highest in children aged 0−5 months of age and 

decrease with increasing age. Published NVSN hospitalization rates from 2000-2004 and recent 

unpublished NVSN estimates from 2016−2020 demonstrate consistency in estimates from the 2 

time periods. Rates in infants 0−5 months of age are slightly higher in the initial surveillance

period. Rates in infants ages 6−11 months, young children ages 12−23 months, and children 

age 24−59 months are slightly higher in the more recent surveillance period. The overall rate in 

children ages 0−59 months and those under 5 years of age is consistent across the 2 

surveillance periods, with overlapping confidence limits.141

NVSN data have also been used to develop estimates of ED and outpatient clinic visits. As with 

hospitalization rates, the highest ED rates have typically been seen in the youngest infants. In 

one surveillance period, rates were nearly equal among infants ages 0−5 months and those 

ages 6−11 months. In the second study period, 2004-2009, the highest rates of ED visits were

in infants ages 0−5 months. Outpatient clinic rates were highest in slightly older infants ages

6−11 months in both surveillance periods.142 A closer look at RSV-associated hospitalization 

rates in children ages 0−11 months demonstrates that the highest incidence of RSV-associated 

hospitalization occurs in infants ages 1 and 2 months and then decreases with increasing 

age.143

136 Thompson et al, JAMA, 2003 137 Hansen et al, JAMA Network Open, 2022; and McLaughlin et al, J Infect Dis, 2022 138 Hall et al, NEJM, 2009 139 Hall et al, NEJM, 2009 140 McLaughlin et al, J Infect Dis, 2022 141 2000-2004: Adapted from Hall et al, NEJM 2009; 2016-2020: CDC unpublished data 142 Hall et al, NEJM, 2009; and Lively et al, J Ped Infect Dis Soc, 2019 143 2000-2005: Adapted from Hall et al, Pediatrics 2013; 2016-2020: CDC unpublished data
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Because of the high incidence of severe disease in the first months of life, RSV prevention

products have focused on maternal immunization and immunoprophylaxis with monoclonal 

antibodies. Palivizumab (Synagis®) is the only RSV prevention product currently licensed in the 

US. It is a humanized monoclonal IgG antibody directed against F glycoprotein. It requires

monthly administration due it to its short half-life of 28 days. Initial clinical trials demonstrated 

55% efficacy against RSV-associated hospitalization in preterm infants and infants with chronic

lung disease (CLD)144 and 45% efficacy against RSV-associated hospitalization in infants with 

congenital heart disease (CHD).145 Currently, the AAP recommends its use in infants less than 

29 weeks gestation during the first year of life, pre-term infants with CLD, infants with

hemodynamically significant CHD, and infants with profound immune compromise.146 This 

recommendation means that approximately 5% of US infants are eligible for immunoprophylaxis 

with Synagis®. However, data suggests that only about 2% receive 1 or more doses.147 There 

currently is no ACIP recommendation on the use of palivizumab.

In conclusion, pre-pandemic RSV seasonality is well-defined with limited geographic variability

in most of the US. RSV is the most common cause of hospitalization in US infants. The highest 

hospitalization rates are in the first months of life and risk declines with increasing age in early 

childhood. Prematurity and other chronic diseases increase the risk of RSV-associated 

hospitalization, but most hospitalizations are in healthy term infants. The only currently licensed 

prevention product targets only 5% of US infants. There are new RSV prevention candidates 

targeting infants in late stages of development, including one product to be introduced by the 

manufacturer during this session.

Discussion Summary

Ms. Bahta asked whether there is any speculation about why higher rates were seen in the 

2016-2020 seasons.

Dr. McMorrow indicated that for the rates overall in children under 5 years of age, there was no 

statistically significant difference. There was a slight increase in the 2016-2020 seasons, but

those were before the pandemic in the older age groups, not in the youngest infants. Again,

they were slight increases of about 10% that were not statistically significant but were not 

considerably different. During the 2021 atypical circulation, slightly higher rates of circulation

were observed after more than a year without activity.

In terms of the 5% eligible and only 2% receiving immunoprophylaxis, Dr. Lee asked whether 

there is any information on whether there are disparities or equity issues in relation to access to 

therapies and if those data would be available from any of the data sources that CDC is aware

of. 

Dr. McMorrow said that most Medicaid-eligible children are provided immunoprophylaxis and 

that she suspects that the children who are not being targeted are on the edge of aging out of 

eligibility. Many of their ACIP colleagues are likely aware of barriers. Given the cost of this 

product, there are important barriers. There are centralized clinics to maximize the distribution 

and utility of the product that often limits its broader availability in the general pediatric office.

144 IMpact-RSV Study group, Pediatrics, 1998 145 Feltes et al, Pediatrics, 2003 146 American Academy of Pediatrics, Red Book, 2021 147 Ambrose et al, Human Vaccines Immuno, 2014
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Epidemiology and Burden of Respiratory Syncytial Virus in Older Adults in the US

Fiona Havers, MD, MHS, FIDSA (CDC/NCIRD) presented an update on the epidemiology and 

burden of RSV in older adults in the US, RSV burden in comparison to influenza, and the impact

of comorbidities on the risk of RSV and severe outcomes. RSV is a frequent cause of severe

respiratory illness in older adults. While it is well-recognized by pediatricians, there is lower

awareness of RSV in adults among HCP and the public. RSV is undetected as RSV testing is 

often not performed, even in hospitalized adults. This is understandable because there is 

currently no vaccine or recommended treatment in most RSV cases. Even though it is often not 

recognized as a cause of illness in adults and there are gaps in recent epidemiologic data for 

RSV, it is known that the burden of disease in older adults is substantial. There are an 

estimated 2.2 million symptomatic illnesses per year,148 approximately 177,000 hospitalizations

annually, and 14,000 deaths in adults ≥65 years of age.149 Even though RSV is often thought of 

as more of a pediatric disease in terms of numbers of hospitalizations and deaths, the burden in 

older adults is very high.150

RSV is a frequent cause of pneumonia in hospitalized adults. This was shown in one large 

study, the Etiology of Pneumonia in the Community Study (EPIC),151 which was a multi-center 

study of patients hospitalized with a community-acquired pneumonia. For patients who met

study criteria, extensive testing for multiple pathogens was undertaken. The study found that 

RSV is a leading cause of community-acquired pneumonia. RSV was detected in 3% of adults 

hospitalized with pneumonia. Although it should be noted that in this study, 62% of patients had 

no pathogen detected. Other studies have shown the proportion of those with pneumonia who 

have RSV to be higher. Regardless, RSV was the fifth most commonly detected pathogen of all 

types in adults hospitalized with community-acquired pneumonia.

There are gaps in estimates of RSV disease burden in older adults and estimates vary by study 

design and can vary widely. There are estimates from studies looking at the incidence of RSV 

among hospitalized patients with annual estimates of hospitalizations per 100,000 population.

There are 2 population-based studies with multi-season estimates from hospitalized patients 

who were tested for RSV.152 A third study uses national syndromic and hospital data to estimate

RSV incidence.153 Despite differing methodologies, all of these studies demonstrate a high 

annual incidence of RSV hospitalization, particularly in patients ≥65 years of age. RSV also 

causes a substantial burden of outpatient disease in adults. Looking at data on rates of 

medically attended visits for RSV in adults ≥60 years of age over 10 seasons, investigators 

tested patients who presented to outpatient clinics with acute respiratory infections and found 

that among those, 11% had RSV. Among those with RSV, 19% had a serious outcome defined 

by the investigators as hospitalization, ED visit, or pneumonia. Rates were nearly 2 times higher 

among patients with chronic cardiopulmonary disease compared to those without underlying 

diseases.154 

148 Adapted from Falsey et al, NEJM (2005) 149 Falsey et al, NEJM (2005) 150 Thompson et al, JAMA, 2003; Hansen et al, JAMA Network Open, 2022; Hall et al, NEJM, 2009; and McLaughlin et al, J Infect 

Dis, 2022 151 Jain S et al. N Engl J Med 2015;373:415-427 152 1 Branche AR, et al. Clin Infect Dis. 2021. doi: 10/1093/cid/ciab595. [Epub ahead of print]; Funding: Merck. Hospitalized adults ≥ 

18 years old with ≥ 2 ARI symptoms or exacerbations of underlying cardiopulmonary disease in Rochester, NY and NYC; and 

Widmer, K. et al. JID 2012; 206:56-62. Funding: NIH/CDC. 153 Matias, et al. BMC Public Health, 2017 Mar 21;17(1):271. Funding: GSK 154 Belongia, et al. Open Forum Infect Dis, Volume 5, Issue 12, December 2018, ofy316, https://doi.org/10.1093/ofid/ofy316 
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Among adults ≥65 years of age in the US, RSV is associated with a somewhat similar burden of 

disease as influenza. To put RSV burden in context, these pyramids compare published 

estimates for influenza on the right in blue compared to RSV on the left in gray:155

For influenza, the data shows the range of point estimates for the 2015-2016 through the 2019-

2020 seasons. The burden of disease varies annually for both RSV and influenza. While there 

are limited recent data on RSV burden, the burden of RSV in older adults for illnesses,

hospitalizations, and deaths are in a similar range as those for influenza generally speaking

based on these estimates. Notably, influenza has widely used vaccines without which the

burden of influenza would be much higher.

Data from other studies have demonstrated similar RSV influenza hospitalization rates in older 

adults. Data from one of the studies looked over 3 seasons at hospitalized patients.156 Among 

this population who was highly vaccinated with influenza vaccine who had acute respiratory 

illnesses who were tested for both pathogens, 6.1% had RSV and 6.5% had influenza. Of note, 

investigators found that hospitalized patients with RSV had clinical outcomes that were as or 

more severe than those who were hospitalized with influenza as measured by length of stay,

ICU admission, mechanical ventilation, or death.

Data from the Respiratory Syncytial Virus Associated Hospitalization Surveillance Network 

(RSV-NET), a population-based surveillance network that covers 8.6% of the US population in 

12 states,

157 provide information about clinical outcomes and co-morbid conditions. All cases 

included had a laboratory-confirmed, RSV-associated hospitalization based on clinician-driven 

testing. Based on RSV-NET data from 2014-2018,158 94% of adults hospitalized with RSV over

these 3 seasons had an underlying condition and nearly half (48%) had ≥3 conditions.

Cardiovascular disease, chronic lung disease, and diabetes were the 3 most frequent

underlying medical conditions among approximately 5,000 patients. Again, these were among 

patients who had clinician-directed testing. While patients with underlying medical conditions 

may be more likely to be tested for RSV than those who do not have underlying conditions, the 

proportion of patients hospitalized for RSV who have co-morbid conditions is very high.

155 1) Falsey et al, NEJM (2005); 2) Adapted from Falsey et al, NEJM (2005); 3) Estimated Influenza Disease Burden 2015-2016 

through 2019-2020, CDC (2022): https://www.cdc.gov/flu/about/burden/past-seasons.htm 156 Widmer et al, JID (2012) 157 Oregon, California, Utah, Colorado, New Mexico, Minnesota, Michigan, Tennessee, Georgia, New York, Connecticut, Maryland 158 Source: CDC unpublished data.
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Co-morbid conditions greatly increase the risk of hospitalization from RSV. One condition that 

clearly increases risk is congestive heart failure. Data from a published study with RSV-NET 

data from 2015-2017159 looked at population-based rates of RSV-associated hospitalizations 

among patients with congestive heart failure. Overall, 28% of hospitalized RSV cases had 

congestive heart failure and hospitalization rates were 8 times higher in patients with congestive 

heart failure compared to those without. The difference between the groups was larger in those 

who were 50 to 64 years of age at 14 times higher rates in those with congestive heart failure 

compared to those without in that age range. This is compared to adults ≥65 years of age who 

had rates 3.5 times higher in those with congestive heart failure compared to those without.

Immunocompromised adults are also at increased risk of severe disease from RSV, including 

LRTIs, ICU admission, and death. The greatest risk is among lung transplants160 and hemolytic 

cell transplant (HCT) patients,161 as well as other immunocompromised populations such as 

those receiving chemotherapy for leukemia or lymphoma. Incidence of symptomatic illness is 

high in some of these groups. For example, in 2 prospective studies of lung transplant patients, 

the incidence of symptomatic RSV illness was 12% over a 2-year period and 16% over a single 

season.162 Severe outcomes are frequently seen in immunocompromised patients with RSV 

infection. Progression to lower respiratory tract illness is very common and mortality can be very 

high. For example, a study of HCT patients showed that mortality was 26% in those with LRTI

due to RSV.163

Long-term care facility (LTCF) residents are another population who are vulnerable to RSV

infection, which is a frequent cause of respiratory illnesses in this population. It is welldocumented as a cause of severe outbreaks in long-term care facilities.164 For example, 1 study 

showed that 13.5% of all residents of a single facility had symptomatic PCR-confirmed illness in 

a single month during an outbreak.165 RSV in LTCF also contributes substantial disease burden 

and cost to the healthcare system. In an industry-sponsored study using Medicare data to

estimate RSV-attributable hospitalizations among long-term care facility residents, the authors 

estimated that these cost more than $50 million per year, with an average length of stay of 5.3 

days per hospitalization and accumulative hospital stay days of more than 32,000 days per 

year.166

Among all adults hospitalized with RSV, a large proportion are severely ill as measured by the 

proportion admitted to the ICU and the proportion who died. In these RSV-NET data from over 3 

seasons,167 about 19% of hospitalized adults of all ages were admitted to the ICU and 4% died.

The mortality was highest in those ≥65 years of age at 5%. However, the proportion admitted to 

the ICU was high, even in younger patients 18−49 years of age, likely reflecting that younger 

patients hospitalized with RSV are likely to have underlying conditions that make them more 

vulnerable to severe outcomes. In addition, RSV leads to exacerbations of underlying chronic 

disease and long-term sequelae, including contributing to acute myocardial infarctions, strokes,

159 Kujawski SA, Whitaker M, Ritchey MD, Reingold AL, Chai SJ, et al. (2022) Rates of respiratory syncytial virus (RSV)-associated 

hospitalization among adults with congestive heart failure—United States, 2015–2017. PLOS ONE 17(3): e0264890. 

https://doi.org/10.1371/journal.pone.0264890 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0264890 160 Manuel O, et al. Clin Transplant 2019 Sep; 33(9):e13511 161 Chemaly RF. CID 2014; 59 Suppl5; S344-51 162 Weinberg A, et al. Transpl Infect Dis 2010 Aug 1; 12(3):330-5; and Milstone AP, Eur Respir J 2006; 28: 131-137 163 Waghmare A., et. al. JI. 2017;216:1235–44 164 Childs A., et al. BMC Geriatr. 2019 Aug 5; 19(1):210. Funding: Sanofi Pasteur. Caram LB, et al. J Am Geriatr Soc 2009; 57(3):

482-5. 165 Bosco E, et al. JAMA Netw Open. 2021 Jun 1; 4(6): e2111806. Funding: Sanofi Pasteur 166 Bosco E, et al. JAMA Netw Open. 2021 Jun 1; 4(6): e2111806. Funding: Sanofi Pasteur

167 Source: CDC unpublished data
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exacerbations of asthma and chronic obstructive pulmonary disease that can result in a longterm decline in respiratory function, and other long-term sequelae.

In terms of the impact of the COVID-19 pandemic on RSV in adults, looking at data from RSVNET from 2014-2022, the COVID-19 pandemic affected RSV in the 2020-2021 and 2021-2022 

seasons. There was highly abnormal circulation during the pandemic, with almost no RSVassociated hospitalizations in the first year and an atypical surge in Summer and Fall 2021.

CDC continues to monitor whether there are long-term impacts on RSV circulation from the

pandemic that will affect the burden of disease in adults.

To summarize, RSV is a major cause of severe illness in older adults. It is a frequent but often

unrecognized cause of severe respiratory illnesses in this population. The burden of disease is 

comparable to that of influenza, with some variability across seasons. Adults with comorbidities, 

including immunocompromised adults and LTCF residents, are among those at risk for severe 

illness. A high proportion of those hospitalized with RSV have severe outcomes, including ICU 

admission and death. RSV illness can result in long-term health consequences.

Discussion Summary

Ms. McNally expressed interest in understanding household transmission rates from household 

contacts (brothers, sisters, parents) to grandparents. Her understanding is that children can 

have RSV more than once and the symptoms they experience the second or third time can be 

less severe. A runny nose in a 5-year-old could be very dangerous to an infant. Her 

understanding also is that it is important for parents to understand that management of infants 

who become sick is largely supportive care and there is not always treatment that will improve

symptoms once they present to the hospital. From the consumer perspective, she is happy to

see that there has been positive development toward an RSV vaccine.

Dr. Havers responded that there have been limited household transmission studies of RSV in 

children. The attack rate in household transmission studies varies and is likely about 20%, but

varies by age. In younger children, the attack rate can be 45% to 50%. In older adults, it may be 

less. The assumption and understanding are correct that the second and third infections in later 

childhood tend to be considerably less severe and have a lower risk of LRTI and associated 

sequelae. It also is correct that there is no current therapy specific

to RSV that is widely used and highly effective. 

Nirsevimab For The Prevention of RSV Disease In All Infants

Dr. Christian Felter (Sanofi) presented on the nirsevimab program for the prevention of RSV 

disease in all infants. Nirsevimab is being brought forward through a collaboration between 

Sanofi and AstraZeneca. AstraZeneca is responsible for regulatory, clinical, manufacturing, and 

development activities. Sanofi is responsible for commercialization activities. As already stated, 

RSV is the leading cause of hospitalization in infants <1 year of age. This is true whether the

child is born premature or term or if they are born in April or December. Despite this, the current 

approach to RSV prevention in infants is a risk-based one, which means that 98% of infants do

not get prevention for RSV. There are many reasons for this, such as the feasibility of the

implementation of a large-scale RSV prevention program. It is clear that what is being done

currently does not address the needs of a majority of infants.
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However, Sanofi and AstraZeneca are on the cusp of a new era where protection from RSV can 

be made available to all infants. To realize this vision, several conditions have to be met. The 

WHO has told them what some of these conditions are. First, a product needs to be indicated

for the prevention of RSV disease in the first year of life to ensure that severe disease is

examined. Second, the primary target population aims to protect most infants during their first 

RSV season. Third, a single dose must provide protection from birth. Fourth, safety must be 

akin to other vaccines that are given at birth. Fifth, efficacy must be at least 70% against severe 

disease and protection must be for at least 5 months.

In the US, more than half a million infants receive medical attention for an RSV LRTI each 

year.168 Most of these cases are in infants who were healthy and born at term. In addition, RSV 

does not discriminate based on when an infant was born, it remains the leading cause of 

hospitalization regardless of when an infant is born.169 Nirsevimab is a recombinant monoclonal 

antibody170 that is targeted at the RSV F protein in its prefusion conformation. It has a 

modification that prolongs the half-life, making it possible to prevent RSV throughout the entirety 

of the RSV season with a single dose by tripling the half-life of the antibody.

The nirsevimab clinical development program consists of 3 pivotal studies that, when taken 

together, span the entirety of the infant population.171 The most recent study is the MELODY 

study, which looked at the safety and efficacy of nirsevimab in late preterm and healthy term 

infants. The Phase 2b study examined the safety and efficacy of the product in the early preterm 

infants who are not currently eligible for palivizumab. The program completed its look at all 

infants with the MEDLEY study, which was the head-to-head safety and pharmacokinetic study 

in the Palivizumab-eligible population, which included children with chronic lung disease

at prematurity or congenital heart disease. MEDLEY and the Phase 2b study that both looked at 

the efficacy of nirsevimab and had nearly identical study designs with the notable exception that 

the MELODY study extended its surveillance through the second RSV season. The primary 

endpoint of both of these studies was the relative reduction in the instance of medically attended

LRTI caused by RT-PCR-confirmed RSV at 5 months. The secondary endpoints were the 

relative reduction in hospitalization, safety, pharmacokinetics, and anti-drug antibodies. Infants 

in the Phase 2b study received either nirsevimab 50 mg or placebo. The Phase 2b study results 

informed the dosing in the MELODY study, where infants under 5 kilograms received 50 mg and 

those above 5 kilograms received 100 mg. Because of the complementary populations and the

matched study designs, the investigators plan to look at the pooled efficacy of these 2 studies to 

show the effect of nirsevimab in all infants not eligible for palivizumab.

Now turning to COVID-19. As discussed with so many things, COVID-19 had an immense,

although indirect, impact on RSV circulation. The lockdowns and the use of non-pharmaceutical 

interventions for the prevention of COVID-19 reduced the circulation of RSV to near zero in

early 2020. The MELODY study began in July 2019 and enrolled 1,027 subjects in the 2019 

Northern Hemisphere RSV season. The study continued into the Southern Hemisphere, where 

462 subjects were enrolled in South Africa. However, there were no cases in either area. Since 

it could not be predicted when RSV circulation would resume, the trial was paused and 

discussions with the FDA were undertaken. It was agreed that the 1,490 subjects enrolled 

before the pause would be evaluated as the primary efficacy cohort, later noted as Cohort 1.

168 Rainisch G, et al. Vaccine. 2020;38(2):251-257 2. Zhu Q, et al. Sci Transl Med. 2017; 9(388) 169 Rainisch G, et al. Vaccine. 2020;38(2):251-257; and Zhu Q, et al. Sci Transl Med. 2017; 9(388) 170 Rainisch G, et al. Vaccine. 2020;38(2):251-257 2. Zhu Q, et al. Sci Transl Med. 2017; 9(388); and 9. Domachowske JB et al, 

Pediatr Infect Dis J. 2018;37(9):886-892 171 1) Hammitt LL,et al N Engl J Med. 2022 Mar 3;386(9):837-846; 2) Griffin MP, et al. N Engl J Med. 2020 Jul 30;383(5):415-425; 

and. 3) Domachowske Joseph et al. N Engl J Med 2022 Mar 386:9, 892-894
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RSV circulation has since resumed as has the MELODY trial, which has now completed its 

enrollment of the second cohort to get to the originally planned 3,000 subjects. The evaluation 

of the safety and efficacy data is ongoing, with publication expected before the end of 2022.

In both the MELODY and the Phase 2b studies, the primary efficacy endpoint was the relative 

reduction in medically attended LRTI caused by RSV. In the MELODY study, the result was a 

74.5% reduction. This is similar to what was seen in the Phase 2b study. It is important to note 

that in the Phase 2b studies, all subjects were given nirsevimab 50 mg regardless of their

weight. When analyzing the pharmacokinetics along with the efficacy results, it was clear that 

those over 5 kilograms needed a higher dose. This was taken into the MELODY study, wherein 

those above 5 kilograms receive 100 mg. The secondary endpoint reported for both study was 

hospitalization due to RSV LRTI. There was a strong result in the Phase 2b study but a nonsignificant result in the MELODY study. It is important to note that this was due to 

underpowering because of the study interruption.

The full dataset will be forthcoming shortly. These studies were not planned to be taken in 

isolation. As mentioned previously, the Phase 2b and MELODY studies essentially were 2

halves of the same study, with one looking at pre-term infants and the other at term. The study 

designs were similar and equally important, nirsevimab was the protection itself rather than the 

stimulation of protection. It functions in the same manner, regardless of gestational age, by 

directly blocking the entry of RSV at the cellular level. For those reasons and because the

product is designed to be used in all infants and not in a particular subpopulation, the studies 

were combined based on a pre-specified analysis plan.

As stated in the introduction, the WHO has said that efficacy against severe RSV disease must 

be examined and efficacy proven. Based on the results of the combined analysis when the

efficacy of nirsevimab is examined in all cases of RSV LRTIs, as well as the subgroup of all 

LRTIs that resulted in hospitalization and those that were classified as very severe (meaning 

that the infant required supplemental oxygen or intravenous fluids), the efficacy is consistent 

regardless of the subpopulation being examined. This is in line with the mechanism of action of 

the product, which does not rely on the generation of an immune response but rather on the 

direct protection of the infant. The efficacy of nirsevimab against all medically attended RSV 

LRTI is 79.5%. Regardless of how the data are examined (e.g., age at randomization, 

geography, or gender), the answer is essentially the same. Another important factor when 

evaluating any potential protection from RSV is the durability of that protection. Protection from 

the nirsevimab is consistent across the 5 months of a normal RSV season. At 5 months, the

curves continue to diverge. There are now additional data suggesting that protection lasts

beyond 5 months.

While a great deal of focus is rightfully put on RSV hospitalization, it is important to look at the

burden that RSV presents in the outpatient setting as well. Looking at the impact of nirsevimab 

on outpatient visits for all-cause medically attended LRTI in the infants from the MELODY study

and the number of antibiotics prescribed over the season, children receiving nirsevimab had

received less courses of antibiotics over the season regardless of indication. This is perhaps

because nirsevimab prevents the bacterial infections that may be associated with RSV, or 

perhaps it is because these children seek medical attention less frequently and hence there is

less over-prescribing. Overall, nirsevimab has a favorable safety profile and one that is 

comparable to placebo or palivizumab, depending on the study. None of the SAEs or deaths 

were considered by the investigators to be related to the product. With regard to

hypersensitivity, there was 1 case of a cutaneous reaction to nirsevimab in the MELODY study.
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In conclusion, RSV represents a significant yearly burden on the healthcare system in the US

and is the leading cause of hospitalization in infants, regardless of the month of birth. Severe 

RSV disease is unpredictable, with most medically attended cases occurring in healthy infants 

born at term. This means that despite all infants being at risk of RSV disease, only 2% currently 

are being protected. All infants need direct protection from RSV regardless of their gestational 

age or when they were born. Nirsevimab is designed to be that protection for all infants. The 3

major clinical trials taken together demonstrate the efficacy of the product in preventing RSV in 

all infants, with more data that will complete the story in the near future. Nirsevimab also has 

been shown to have a favorable safety profile across all 3 studies and is designed to be easily

implemented with a single injection, either at birth or alongside routine infant immunization.

Discussion Summary

Dr. Poehling requested additional information about how nirsevimab is administered, the route 

of administration, and the dose volume. 

Dr. Villafana indicated that the 15 mg dose is half a mL and the 100 mg dose is 1 mL that will be 

in the form a prefilled syringe.

Dr. Sanchez emphasized the need for a product like this for prevention of severe RSV and 

medically attended RSV, so this is very exciting news. He requested a definition for “medically 

attended LRTI” and what definitions were used for the trial outcomes.

Referring to back-up Slide 20, Dr. Leach indicated that the case definition of medically attended 

RSV LRCI included all children presenting for medical care. They were RSV-confirmed by a 

central laboratory PCR assay and were ensured to have had lower respiratory tract involvement 

by chest examination, looking for a clinical sign. Each of these children also had at least 1 sign 

of clinical severity. These include raised respiratory rate, hypoxemia, acute hypoxia or 

ventilatory failure, new onset apnea, nose flaring, retractions, grunting, dehydration due to 

respiratory distress. “Very severe” included a subset of the children who were admitted to the 

hospital who either required oxygen during their hospital stay or required IV fluids.

Dr. Daley asked what the age distribution was among those who were vaccinated at birth or 

within the first 2 months of life. In addition, he asked what was known about vaccinating in the 

Spring for protection the following season (e.g., 8 months before the typical respiratory season), 

acknowledging that this was incredibly complicated due to the COVID-19 pandemic.

Dr. Leach indicated that in the primary analyses that have been reported to date, more than 500 

neonates (less than 28 days of age) were enrolled who would have been randomized to either 

nirsevimab or to comparator. Going forward, additional data will be coming in to support this in 

the ongoing MELODY trial. In the 2 trials, MELODY and MEDLEY, infants enrolled in the 

preterm trial were less than 35 weeks gestational age and the late preterm and term were 35

weeks gestational age and above. There were definitely neonates in substantial numbers in 

both trials. All of the trials were designed to immunize prior to the RSV season. The data

presented here were censored after 5 months when the primary endpoint was examined. 

Serendipitously in the COVID-19 epidemic, RSV disappeared. The investigators had immunized 

over 500 children in South Africa, who they were able to follow. No RSV season appeared

during that time. When RSV reemerged after 5 months of follow-up, there was an indication of

protection in those children. While it was not statistically significant, it was a very intriguing 

observation.
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Dr. Felter indicated that these data are shown on back-up Slide 19. Back-up Slide 18 shows the 

demographic breakdown by gestational age group. To add to the question regarding the 

definition of medically attended, this could include medical attention sought in a doctor’s office, 

ED, or hospital in this context.

Dr. Brooks asked for clarity regarding whether all children are being followed for up to a year or 

just out to the 5-month data cutoff. Like Dr. Daley, he wondered about the duration of protection.

Dr. Leach indicated that all children would have been or are in the process of being followed for 

a year. The primary efficacy endpoint reported was over the 5-month period, which is 

anticipated to be the duration of a typical season. All of the children in the clinical studies will be 

followed for a full year of protection. There will be more information on duration of protection 

beyond the 5-month period.

Dr. Sanchez noted that it is important to clarify that this is not a vaccine and that no children are 

being immunized. Thinking about the potential for FDA approval, he asked the age of the 

youngest babies who were medicated.

Dr. Felter confirmed that this is not a vaccine. It is passive immunization through a monoclonal 

antibody that it is meant to be given at birth or at the start of the RSV season for those who are 

born prior to the season.

Dr. Leach indicated that the study protocols allowed for the immunization to be given on the first 

day of life. Though there were not many, a number of children were dosed on the first day of life.

A substantial number of children were immunized in the first week of life.

Dr. Loehr said that his sense was that Sanofi/AstraZeneca were advocating for all babies born

in the hospital in September or October to receive nirsevimab in the hospital, maybe even 

throughout the winter. If they were born in January, they would get it because it is still RSV

season. The goals would be for all outpatients to try to receive it the September/October time 

range.

Dr. Felter confirmed that babies born before the season would be getting nirsevimab as

outpatients in doctors’ clinics. For those born in season, as close to birth and ideally before 

discharge from the hospital would be the proposed implementation time to make sure that they 

got the maximum benefit from the prevention provided.

Dr. Kotton observed that it was interesting for the ACIP to be discussing use of a monoclonal

antibody, which seemed somewhat different than what has been done in the past as far as she 

understood it. The ACIP has not addressed products such as EvusheldTM, which is for

prevention of COVID-19 and has been underutilized. People are confused in terms of the

recommendations. It seems like a loss that the CDC and the ACIP have not taken that on, 

though now it was unclear why they were looking at a monoclonal antibody for RSV. She has 

been involved in the stewardship of palivizumab for years. It is phenomenally expensive, so she 

expressed her hope to see a good cost-benefit analysis with this new monoclonal antibody.

Dr. Poehling requested further information about the Grade 4 events and deaths that were

reported.
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Dr. Leach indicated that in total in all of the pivotal trials, there have been 14 fatalities. Of those,

10 occurred in nirsevimab recipients and 4 were in placebo recipients of placebo. As a 

reminder, randomization was 2:1 in all of the clinical trials. Essentially, the deaths were 

balanced by group. The investigators reported that none of the deaths were related to the 

product. The overall assessment was that the causes of death observed were in line with 

expected mortality rates of that population. She indicated that she was not immediately able to 

respond to the question about Grade 4 events without reviewing the data, though they always 

are concerned about safety. She agreed to follow-up via written response.

Dr. Sanchez wondered whether follow-up beyond a year might be needed. Thus far, the 

experience is anecdotal. Given the lack of RSV during the previous season in the second year 

of age, some of these children were being hospitalized with RSV infection and they were older.

In terms of this anecdotal experience, it is important to know whether some of the very high-risk 

premature infants not only get through their first season, but also are not presenting with more 

severe RSV in their second season.

Dr. Villafana indicated that they followed all of the children through Day 361, but in the MELODY 

study, children are followed through a second RSV season. They will have information from that 

second season of follow-up to share with the ACIP in the future. Though not presented during 

this session, there are data showing that children mount an immune response to natural RSV

infection when dosed with nirsevimab.

MONKEYPOX INFORMATIONAL SESSION

Situational Update

Agam Rao, MD, CAPT USPHS (CDC/NCEZD) introduced this session with some background 

information about monkeypox. Monkeypox is a rare, sometimes life-threatening zoonotic 

infection that is endemic in West and Central Africa. It is caused by monkeypox virus, which is 

an orthopoxvirus. The specific animal reservoir for monkeypox virus is unknown but is probably 

small mammals. It can spread from infected animals to humans and person-to-person through 

respiratory secretions, skin-to-skin contact with infected bodily fluids (e.g., fluid from vesicles

and pustules), and fomites (e.g., shared towels and contaminated bedding). Before 2022, there 

were US cases. In 2003, there was an outbreak linked to small mammals imported from Ghana. 

There were 47 cases associated with that multi-state outbreak involving the upper Midwest US. 

The cause was traced to the spread of monkeypox virus from imported African rodents to pet 

prairie dogs and then to people who had contact with the pet prairie dogs. In 2021, there were 2 

unrelated cases in travelers from Nigeria. The first was in July in Texas and the second was in 

November in a patient who resides in Maryland. These cases were similar to imported cases 

during 2018-2021 in 4 travelers returning from Nigeria to the UK (4), 1 traveler returning from 

Nigeria to Singapore, and 1 traveler returning from Nigeria to Israel. Nigeria experienced a large 

outbreak in 2017 that resulted in cases continuing to occur afterward. There were decades of no 

cases in Nigeria until the outbreak in 2017.

Cases among patients involved in the 2003 US monkeypox outbreak were due to bites and 

scratches for the most part. These individuals had firm, well-circumscribed, deep-seated, and 

painful lesions. Lesion in endemic countries were the same. Everything changed in May 2022. 

The UK had cases in 3 distinct clusters that they announced on May 7th, 14th, and 16th. The first 

was a travel-associated case from a traveler, so it sounded similar to some of the other cases 

seen outside of the African Continent since 2018. The next 3 were from a family cluster of 
ACIP Meeting Summary June 22-23, 2022

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unknown etiology. Given that none of the individuals in the family had actually traveled outside 

of that area, the source remains unknown. On the 16th is when 4 cases were identified at sexual 

health clinics among gay, bisexual, or other men who have sex with men (MSM) and reported 

on. US public health authorities were first notified of a suspected case in Massachusetts on the 

17th in a Massachusetts resident who had traveled to Canada, where CDC had heard that there 

also were cases occurring. The Massachusetts rash began as an anogenital rash with vesicles 

and pustules, which spread to the face in trunk. Testing was done at the Laboratory Response 

Network (LRN) laboratory in Massachusetts, which was positive for non-virial orthopoxvirus 

through the OPX generic positive test.

Since then, cases have steadily increased in the US. As of 2:00 PM ET on 22 June 2022, there 

were 155 cases diagnosed in the US among residents of 24 states and the District of Columbia 

(DC). Cases are updated every day at 2:00 PM ET, so Dr. Rao already knew that the case 

count was somewhat higher than the previous day. The data presented during this session 

focused on the 155 cases from the previous day. These states in which these cases were 

identified are depicted on the following map, with the highest number occurring in California, 

New York State, Illinois, Florida, and Colorado:
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Case patients for whom CDC has information about the data of rash onset are depicted in this 

epidemiologic curve. Of note, the date of rash onset was selected because a lot of the case 

patients involved in this outbreak have not had the typical prodromal symptoms associated with

Monkeypox or the typical symptoms have occurred, but have been very mild and not easily 

recognized:

The earliest date of rash onset was at the beginning of May 2022. The initial cases identified in 

the US were in people who had traveled abroad who attended large gatherings internationally in 

Spain, France, and Germany. As time has gone on, there still have been reports of case 

patients who traveled abroad themselves. However, locally acquired infection is also now 

occurring through local transmission.

In terms of basic demographics among the 155 cases, the median age is 37 years (range 20−76 

years). Most of the case patients are of male sex at birth among whom 56 are cisgender men, 

82 are of unknown gender identity, and 1 refused to identify. CDC has information about maleto-male sexual contact (MMSC) for 120 out of 121 who have reported MMSC but does not have 

information from 29 individuals because that information has not been reported to CDC. There 

are 5 cases for female sex at birth, including transgender males and cisgender women. There 

have been no deaths, nor have any HCP acquired the infection due to providing care for a 

patient.

In terms of clinical presentation, every US patient has had a rash or enanthem. Only 1 patient 

had an enanthem at the time that illness was suspected, and that individual was a contact of 

someone else, which is why it was identified rapidly. The swab from those lesions inside the 

mouth tested positive, but everybody else has gone on to develop a rash on their body. Lesions 

in different phases of development have been seen side-by-side on the same body site, which 

historically has not been reported for monkeypox. The rash is either scattered or diffuse and is 

sometimes limited to 1 body site and mucosal area (e.g., anogenital region or lips/face), while at 

other times it is spread throughout the body. The presenting complaint for some patients has 

been anal rectal pain or tenesmus. Physical examination has yielded visible lesions and 

proctitis. No cases have been seen that have involved people who have not had visible lesions 

somewhere. Prodromal symptoms have been mild or not occurring. Fever and 

lymphadenopathy, which are commonly associated with monkeypox, are not necessarily 

occurring in all of the patients. Some co-infections with sexually transmitted infections (STIs) 

have been seen. A diagnosis of an STI like syphilis or herpes does not rule out monkeypox, 

which has been observed in some of the case patients.
ACIP Meeting Summary June 22-23, 2022

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Despite all of these features that are perhaps not considered typical of classic monkeypox, the 

lesions are still firm, deep-seated, well-circumscribed, and sometimes umbilicated. The lesions 

in the current outbreak are sometimes very small. In this photograph, Panels A and B are from 

individuals in the current outbreak and Panel C is from the 2003 US outbreak:

While the lesions in the current outbreak are consistent with monkeypox, they seem to be much 

smaller and there are some atypical aspects to them. Papulovesicular and pustular lesions are 

being seen side-by-side. Additional images are available that include photographs of lesions in 

the anogenital region.172, 173

CDC guidance to clinicians is changing more information is learned. Guidance was conveyed in 

the previous week through the Health Alert Network (HAN) for clinicians to observe for classic 

monkeypox rash and to obtain swabs from that. In addition, clinicians should observe for rash 

that could be consistent with monkeypox in persons with epidemiologic risk factors, including 

contact with a person or people with a similar-appearing rash or who has been diagnosed with 

monkeypox; close or intimate in-person contact with people in a social network experiencing 

monkeypox activity (e.g., MSM who meet partners through an online website, digital app, social 

event); or a history of recent international travel to a country currently reporting cases. Clinicians 

were alerted to obtain swabs from those lesions, not to rule out co-infection with monkeypox 

when an STI is diagnosed, and to conduct a full body examination when lesions are not 

consistent with classic lesions. CDC has heard that even though not all of the lesions on an 

individual might be consistent with classic presentation, clinicians are finding firm, deep-seated, 

well-circumscribed, sometimes umbilicated lesions somewhere on the body.

Some of CDC’s current priorities are to try to understand the clusters and cases occurring in 

various parts of the country, risk factors for acquiring infection, and outcomes. The CDC 

laboratory is sequencing genomes to try to understand how these might be related to previous 

genomes based on the sequencing that done in Nigeria as part of the work that CDC has done 

for years in Africa, the Democratic Republic of Congo (DRC), and Nigeria. The agency is 

launching retrospective and prospective serosurveys to try to understand whether cases were 

occurring before the cases were identified in the US and before the travel to Europe may have 

occurred. A natural history study is being developed to understand this better. Testing capacity 

is being expanded to commercial laboratories, and CDC is providing case-by-case consultations 

172 Ogoina D et al. Clinical course and outcome of human monkeypox in Nigeria. Clin Infect Dis. 2020; 71(8): 210-214 173 Antinori A et al. Epidemiological, clinical, and virological characteristics of four cases of monkeypox support transmission through 

sexual contact, Italy, May 2022. Euro Surveill. 2022 June; 27 (22).
ACIP Meeting Summary June 22-23, 2022

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for treatment and post-exposure prophylaxis (PEP). These and other agency priorities/activities, 

interim information, and tolls for HCP and public health authorities can be found on the CDC 

website, which being updated regularly as new information is acquired.

Discussion Summary

Dr. Loehr asked Dr. Rao to further explain what was meant by “deep-seated,” which he was 

interpreting to meant that it goes down below the skin and is deeper.

Dr. Rao indicated that it is not superficial the way varicella-zoster looks. It is not something that 

can be unroofed with the fingertip, for example.

Dr. Bell requested additional information about the settings in which transmission is assumed to 

have occurred. She got the sense from the points made during the presentation that this is 

associated with large gatherings or certain specific settings.

Dr. Rao responded that CDC is looking into clusters across the country. It appears in the US to 

be similar to what international scientific communities have observed, that most of the cases are 

occurring in MSM among individuals who seem to have gotten the cases through secondary 

and tertiary spread from having sex with other men. There have been some women who appear 

to have gotten it through intimate contact with men. This continues to be evaluated. In terms of 

large gatherings, there were some large pride events internationally that occurred in the Canary 

Islands, Berlin, and some other places and there seem to be some clusters around that.

Montreal has reported that a bathhouse is associated with many of their cases. Large events in 

the US are being investigated as well. CDC has heard about some private sex parties that have 

been associated with some cases. Worldwide, there have been cases among close contacts

who perhaps shared bedding or towels. Transmission is not just among males and not just 

through close intimate contact. 

To follow-up on Dr. Loehr’s comment about “deep seated,” Dr. Romero learned from historical 

reference that a “thumb sign” was used for smallpox. If the vesicles are particularly tough and a 

thumb can be run over the vesicle without it rupturing like it would with chickenpox, that is the 

deep-seated nature of the vesicle itself. Looking at the pictures Dr. Rao showed, it seemed that

some of them would probably not pass the thumb sign.

Dr. Rao indicated that CDC has heard that none of the vesicles have been superficial like 

chickenpox. Or if they have been, there is possibly co-infection. It is known from CDC’s work in 

Africa that co-infection with varicella does occur with monkeypox.

Dr. Shaffner (NFID) said his historical reference was that smallpox lesions often were described 

as firm or rubbery. He asked whether there is any sense that there might be transmission before 

the rash is present. 

Dr. Rao indicated that this is being assessed as part of the natural history study CDC is 

conducting but is not aware of asymptomatic transmission or transmission before someone 

develops symptoms from years of working on monkeypox at CDC. 

Dr. Goldman (ACP) said was finding the website extremely helpful. He asked whether clinicians 

should contact CDC directly or the health department if they suspect one of their patients has 

monkeypox, and whether samples should be sent to a commercial laboratory.
ACIP Meeting Summary June 22-23, 2022

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Dr. Rao indicated that clinicians should contact their local health departments, which are 

coordinating the obtaining of specimens and sending them to the local LRN laboratory. That 

may change once testing is rolled out to other laboratories, such as commercial laboratories.

This information will be updated on the website.

Medical Countermeasures

CAPT Brett W. Petersen, MD, MPH (CDC/NCEZID) provided an overview of the medical 

countermeasures for monkeypox, first pointing out that a number of medical countermeasures 

have been stockpiled for smallpox and can be used for other orthopoxviruses like monkeypox.

There are 2 vaccines available, JYNNEOS and ACAM2000. Tecovirimat, a first-line agent; 

vaccinia immune globulin intravenous (VIGIV); and cidofovir are treatments that are available in 

the Strategic National Stockpile (SNS). 

The first medical countermeasure is JYNNEOS,174 which is a live vaccine produced from the 

strain Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN). This is an attenuated, nonreplicating orthopoxvirus. It is also known as in IMVAMUNE, IMVANEX, or MVA. This vaccine 

was licensed by FDA in September 2019 for the prevention of smallpox and monkeypox disease 

in adults ≥18 years of age. CDC is developing an Expanded Access Investigational New Drug 

(IND) protocol to allow the use of JYNNEOS for monkeypox in pediatric populations. Currently, 

1 pediatric patient has received JYNNEOS under a Single Patient IND protocol. The second 

countermeasure is ACAM2000,175 which is a live vaccinia virus vaccine. This is a replicating 

virus. ACAM2000 was licensed by FDA in August 2007. It replaced the previously licensed 

vaccine Dryvax. ACAM2000 is specifically licensed for active immunization against smallpox 

disease for persons determined to be at high risk for smallpox infection. Consequently, CDC 

does hold an Emergency Access IND protocol to allow the use of ACAM2000 for Non-Variola 

Orthopoxvirus infection (e.g., monkeypox) during an outbreak.

There are significant differences between these 2 vaccines. The first and perhaps most 

important is the vaccine virus themselves, with ACAM2000 being a replicating vaccine and 

JYNNEOS being replication deficient. Consequently, ACAM2000 does produce a “take” or a 

vaccine site lesion at the site of inoculation and JYNNEOS does not. And as such, ACAM2000 

does have a risk of inadvertent inoculation and autoinoculation from the infectious virus that is 

present in these vaccine site lesions. ACAM2000 also has a risk for SAEs due to uncontrolled 

replication, which is not expected to occur with JYNNEOS. With respect to cardiac AEs, 

ACAM2000 has myopericarditis reported at a rate of 5.7/1,000 primary vaccinees.

Myopericarditis has not been reported in association with JYNNEOS vaccine. If there is any risk 

present, it is believed to be lower than that for ACAM2000. With respect to effectiveness, 

ACAM2000 was licensed by FDA based on comparisons of the immunologic response and 

“take” rates to Dryvax, the previously licensed vaccine. JYNNEOS similarly was assessed by

comparing the immunologic response to ACAM2000 and also taking into account animal 

studies. For administration, ACAM2000 is given percutaneously by a multiple puncture 

technique in a single dose. JYNNEOS is given subcutaneously in 2 doses separated by 28

days.

174 https://www.fda.gov/vaccines-blood-biologics/jynneos 175 https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5708a6.htm; https://www.fda.gov/media/75792/download
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With respect to vaccine supply, as of June 14, 2022, the SNS held more than 36,000 courses

of the 2-dose regimen for JYNNEOS that are available for immediate release. To date, a little 

more than 4,000 courses have been requested and distributed to a total of 28 jurisdictions.

There are an additional 150,000 courses available at the manufacturer that are expected to be 

delivered over the next few weeks. In addition, there are 500,000 courses available at the

manufacturer awaiting release that are expected to be delivered this year. There has been an 

order for 250,000 additional courses to be manufactured from existing bulk vaccine, which also 

are expected to be delivered later this year. This comes from a total of 7.9 million courses of 

bulk drug that could be filled and finished upon request by the US Government (USG). For 

ACAM2000, there are currently more than 100 million doses in the SNS.176

In terms of recommendations for pre-exposure prophylaxis (PrEP), ACIP voted in November

2021 to recommend vaccination for select persons at risk for occupational exposure to

orthopoxviruses. These recommendations were published in June 2022 in a Policy Note, which 

is currently available.177 In those recommendations, people who are recommended to receive 

PrEP include the following:178

 Clinical laboratory personnel who perform testing to diagnose orthopoxviruses, including 

those who use PCR assays for diagnosis of orthopoxviruses, including monkeypox virus.

 Research laboratory workers who directly handle cultures or animals contaminated or 

infected with orthopoxviruses that infect humans, including monkeypox virus, replicationcompetent vaccinia virus, or recombinant vaccinia viruses derived from replicationcompetent Vaccinia virus strains.

 Certain healthcare and public health response team members designated by public health 

authorities to be vaccinated for preparedness purposes.

PrEP for healthcare workers is possible under shared clinical decision-making. At this time,

most clinicians in the US and laboratorians not performing the orthopoxvirus generic test

to diagnose orthopoxviruses are not advised to receive prthopoxvirus PrEP. Laboratorians

should consult with laboratory biosafety officers and supervisors to identify risks and

precautions, depending on the type of work that they are doing. Clinicians and laboratorians

should use recommended infection control practices. ACIP contraindications for ACAM2000 and 

JYNNEOS for PrEP are outlined in the following table:

176 https://aspr.hhs.gov/ASPRBlog/Pages/BlogDetailView.aspx?ItemID=432; https://www.bavariannordic.com/investor/news/news.aspx?news=6584 177 https://www.cdc.gov/mmwr/volumes/71/wr/mm7122e1.htm 178 https://www.cdc.gov/poxvirus/monkeypox/clinicians/smallpox-vaccine.html 
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In terms of CDC’s response in the current outbreak, the agency is focusing on tried-and-true 

public health measures, including robust surveillance to identify cases and confirm through 

laboratory diagnosis, followed by containment through isolation of cases and contact tracing, 

and vaccination of close contacts with PEP based on a risk exposure assessment for which 

guidance is available on the CDC website.179 This includes PEP being recommended for 

individuals with a high degree of exposure, those with an intermediate degree of exposure to be

recommended PEP based on an individual basis to determine whether benefits of PEP

outweigh the risks. It is important to note that brief interactions and those conducted using

appropriate personal protective equipment (PPE) in accordance with Standard Precautions are 

not high risk and generally do not warrant PEP. 

With respect to other vaccine strategy considerations, CDC is aware that there are jurisdictions 

with larger numbers of cases that are reporting high percentages of contacts that cannot be 

identified. Several are considering, planning, and even implementing expanded vaccination

programs at this time. Many are following similar approaches to strategies being used in

Montreal and the UK. However, there are currently limited supply of JYNNEOS. CDC, in 

planning for expanded vaccination in the US, is carefully considering how best to use these

limited supplies. The agency has heard from some jurisdictions that there are concerns about 

potential serious AEs with the use of ACAM2000, especially considering that milder disease is 

commonly being reported in this outbreak. CDC is working with the ACIP and federal, state, 

local, and other community partners to move forward as quickly as possible to provide

recommendations to expand vaccination. The EtR Framework is being used to structure these 

deliberations and guide the development of vaccine strategies.

In terms of treatment considerations for monkeypox, it is important to start with the statement

that many individuals infected with monkeypox virus have a mild self-limiting disease course, 

even in the absence of specific therapy. The prognosis for monkeypox does depend on multiple 

factors, including previous vaccination status, initial health status, and concurrent illnesses or

comorbidities. With that in mind, CDC has provided some treatment considerations for

monkeypox and recommends considering treatment following consultation with CDC for the 

following: 

 Persons with severe disease (e.g., hemorrhagic disease, confluent lesions, sepsis, 

encephalitis, or other conditions requiring hospitalization).

 Persons who may be at high risk for severe disease:

− People with immunocompromising conditions (e.g., HIV/AIDS,

− leukemia, lymphoma, generalized malignancy, etc.)

− Pediatric populations, particularly patients younger than 8 years of age

− Pregnant or breastfeeding women

− People with a history or presence of atopic dermatitis and people with other active

exfoliative skin conditions

− People with one or more complication

 Persons with monkeypox virus aberrant infections that include its accidental implantation in 

eyes, mouth, or other anatomical areas where monkeypox virus infection might constitute a 

special hazard (e.g., the genitals or anus) 

179 https://www.cdc.gov/poxvirus/monkeypox/clinicians/monitoring.html#exposur 
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133

Tecovirimat180 is an antiviral medication that is approved by the FDA for treatment of human

smallpox in adults and pediatric patients weighing at least 3 kilograms. This is also known as 

TPOXX or ST-246. An oral capsule and IV formulations were approved by FDA in July 2018 and 

May 2022, respectively. Tecovirimat is indicated for the treatment of human smallpox only. CDC 

does hold an Emergency Access IND protocol to allow the use of Tecovirimat for non-virial 

orthopoxvirus infections, including monkeypox. Currently, Tecovirimat is available from the SNS 

as an oral capsule formulation or an intravenous vial. VIGIV181 is licensed by the FDA for the

treatment of complications due to vaccinia vaccination, including eczema vaccinatum, 

progressive vaccinia, severe generalized vaccinia, vaccinia infections in individuals who have 

skin conditions, and aberrant infections induced by vaccinia virus (except in cases of isolated 

keratitis). CDC similarly holds an Emergency Access IND protocol to allow the use of VIGIV for 

non-virial orthopoxvirus infections, including monkeypox. This product may be used in unique 

cases, severe cases, as adjunctive therapy, or otherwise. The SNS holds Cidofovir, also known 

as Vistide,182 which is an antiviral medication that is approved be FDA for the treatment of 

cytomegalovirus (CMV) retinitis in patients with Acquired Immunodeficiency Syndrome (AIDS). 

CDC has an Emergency Access IND protocol to allow for use of this product for monkeypox.

CDC is available for consultations to assist with medical countermeasure utilization, including 

appropriate vaccine and antiviral use. Clinicians can work with their state or territorial health

authorities to request vaccines, Tecovirimat, VIGIV, or Cidofovir. Health departments can reach 

out to CDC consultants through the CDC Emergency Operations Center (EOC). 

Discussion Summary

Dr. Kotton inquired as to whether brincidofovir (BCV), a liquid preparation of cidofovir that is 

much better tolerated and is approved for smallpox, has been considered for use with

monkeypox. 

Dr. Petersen indicated that brincidofovir is a lapidated formulation of cidofovir that is licensed by 

FDA for treatment of smallpox. CDC is working with government agencies and the manufacturer

of this product, which is not currently available in the SNS, to investigate ways to make it 

available if needed for monkeypox. In addition, CDC is working with regulatory authorities to 

make sure that the agency has a regulatory mechanism to use it, given that it is not licensed for 

monkeypox, such as the Expanded Access IND protocol. 

Dr. Chen asked whether there are similar limits for the tecovirimat and the VIGIV products as 

there are for the vaccines. He also observed that the New York City Department of Health has 

been coordinating with the CDC and is trying to stage a vaccination clinic in Manhattan and 

asked whether there are similar movements by other health authorities in other regions that are 

also trying to access vaccines and/or therapeutics and if perhaps these need to be wider 

dissemination more rapidly regarding those types of activities. 

Dr. Petersen indicated that the precise numbers of tecovirimat, VIGIV, and cidofovir stockpiles 

have not been released, but there is sufficient quantity. CDC does not expect any supply

limitations in any of those medical countermeasures. He confirmed that CDC is coordinating 

with New York City and other jurisdictions that are working to expand their vaccination 

programs. Fortunately, they are working with the SNS, which is able to ship these medical 

countermeasures very rapidly. In general, it is possible to get these products where they need to 

180 https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208627s000lbl.pdf 181 https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/vaccinia-immune-globulin-intravenous-human 182 https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/020638s003lbl.pdf 
ACIP Meeting Summary June 22-23, 2022

134

go within 28 hours. However, there are some supply limitations with JYNNEOS that CDC is 

working to address to make sure that this medical countermeasure is being provided and used 

in an optimal and equitable fashion.

Dr. Sanchez asked how to access the vaccines and/or medications from a practical standpoint 

in terms of the chain of events and whether requests all go through local health departments 

who contact CDC.

Dr. Petersen replied that CDC is requesting that medical countermeasure requests come from

health departments so that appropriate public health authorities are aware of what is happening 

and what is available in their jurisdictions. Clinicians on the ground, as with any suspect cases,

are advised to go directly to their local and state public health authorities.

Dr. Maldonado (AAP) said it was her understanding that the WHO is considering designating 

this as a Public Health Emergency of International Concern (PHEIC), and she imagined that 

CDC was involved in those conversations as well. Given that they were approaching the end of 

this ACIP meeting and we may not receive updates in the near future, she asked whether there

might be anything different about recommendations from CDC that this international designation 

might lead to. In addition, it seemed to her that this is not the traditional presentations for 

orthopoxvirus or monkeypox virus infections seen on the African subcontinent, particularly for 

children. She asked whether there have been cases reported in children that are the usual,

typical manifestation or this atypical manifestation and whether there should be concerns about 

other precautions that would need to be taken for children regarding treatment or prophylactic

interventions.

Dr. Petersen confirmed that the WHO convened a meeting earlier in the day. On their agenda 

was a discussion of whether to declare this current monkeypox outbreak a PHEIC. CDC was 

participating in that meeting, though he had not yet heard the readout from that meeting to know 

whether that would occur. Ultimately, that is a decision for the WHO Director General. If a 

PHEIC is declared and the US follows suit and declares a public health emergency as well, that 

could change some of the regulatory mechanisms in terms of these medical countermeasures,

opening up the possibility that they may be used under an EUA or under Emergency Use 

Instructions (EUI).

Dr. Rao indicated that there have not been any cases in children in the US. Internationally, CDC 

has heard very little about cases in children. Cases that have occurred in Nigeria, in general,

have been somewhat strange for other reasons. This particular clade of monkeypox has not

resulted in more severe illness and has not spread person-to-person as much. Even before the 

2022 cases were identified, the West Africa clade associated with Nigeria infections has been a 

somewhat unusual in that some deaths have been reported and there has been person-toperson spread, including in settings like prisons and among household members. An imported 

case resulted in secondary cases, including in one healthcare worker. It is difficult to know for 

sure why this is presenting unusually in terms of whether it is something related to what has 

been seen for the last few years in West Africa or if it is something different. CDC is trying to 

understand that. At this point, CDC is relying on what is known from the agency’s work before 

2022 in Africa. While the clinical presentation itself has been similar, the illness has sometimes

been more severe in children.
ACIP Meeting Summary June 22-23, 2022

135

Dr. Drees (SHEA) noted that the PPE recommended for care of suspected monkeypox cases 

includes gloves, eye protection, and a respirator. However, a healthcare provider may not

realize that they should be worried about monkeypox until they are actually examining the

patient and seeing typical lesions. They would not necessarily have a respirator, especially in 

outpatient locations. But she recalled from the presentation that this would not be considered an 

exposure in terms of the use of PEP. This seemed like a disconnect, so she wanted to confirm 

that this was correct. Thankfully, people in healthcare are still masking routinely, but she 

wondered about what advice CDC would give for healthcare workers who saw the patient

initially without use of the full PPE in terms of self-monitoring.

Dr. Rao said that she and Dr. Petersen both were involved in developing the initial guidance. 

With the growth of this outbreak, there have been others from CDC’s Division of Healthcare

Quality, and Promotion (DHQP) and other groups taking the lead on that. In the interest of not 

misspeaking, they offered to check and get back to ACIP on that.

Dr. Petersen added that the risk exposure assessment is currently being revised and will

provide specific recommendations for healthcare workers as well as community members at 

large. Some of that information will be revised in the near future.

Dr. Fryhofer (AMA) said she had read that brincidofovir has an improved safety profile over the 

cidofovir and requested additional information about that and also what side effects to expect 

with these antivirals.

Dr. Petersen indicated that cidofovir does carry a risk of renal toxicity and is administered

intravenously in conjunction with cimetidine for renal protection. In contrast, brincidofovir is 

orally available and in clinical trials has not shown the same renal toxicity and has shown some 

potential for hepatoxicity as well as some GI side effects. But in general, the safety profile

of brincidofovir does show less severe side effects compared to cidofovir. Tecovirimat has

shown to be quite safe and well-tolerated without any specific safety concerns for SAEs.

Dr. Long noted that the epidemiology of the cases described gives a somewhat different image

of potential spread to the population in general and through non-sexual contact. She asked if 

there is reason to believe that this virus is transmissible without very close personal contact, and 

what CDC’s expectations are of cases outside of sexual transmission. Her concern is about the 

likelihood that the general US population might be susceptible and if they should be worried 

about usual casual contact with one another.

Dr. Rao indicated that the cases CDC is aware of have occurred through direct skin-to-skin 

contact, contact with fomites (towels, bedding), and close contact with a household member. 

Historically, the recommendations have been that monkeypox can be spread through direct

contact as well as through close proximity because of secretions. Someone in close proximity 

for a prolonged period of time to somebody else could be exposed through secretions. There is 

no reason at this time to suspect spread in any other way. It is not even clear whether 

transmission is through seminal fluids or if is through the close contact that occurs when people 

have intimate contact. CDC is trying to understand this and is planning semen and other studies 

to understand this better. At this moment, all signs are that it has still not spread to a large

number of people, and it is believed that a lot of the case patients have had a large number of 

contacts. CDC is trying to get to the bottom of exactly how many contacts and how many people 

it might have been spread to, but it appears to be a small number of exposed contacts who 

have gotten it and their contact has been pretty intimate. There is no reason at this time to 
ACIP Meeting Summary June 22-23, 2022

136

suspect that this is a risk to the wider population. The risk to the general public is believed to be 

very low at this time.

Ms. Howell (AIM) pointed out that the awardees in the 64 immunization programs have been 

rolling out COVID-19 vaccines, which has been taking a lot of their time. If a larger campaign 

may be needed in the future for JYNNEOS or other vaccination, planning assumptions or 

guidance would be appreciated as early as possible. A lot of the COVID-19 vaccine funding is 

very specific to COVID-19 vaccine and cannot be used for any rollout of a monkeypox vaccine 

initiative.

Dr. Fryhofer (AMA) noted that the CDC website states that monkeypox also can be spread 

through respiratory secretions during prolonged face-to-face contact for which she requested 

further explanation.

Dr. Rao reiterated that DHQP has taken this over because it is their area of expertise, but this is 

about close contact, such as being within 6 feet for a prolonged period of time and the 

opportunity to be exposed to someone’s saliva or droplets from respiratory secretions. Someone 

kissing and saliva is what they are trying to get at with that.

Thinking about the fact that there have been no deaths among the 155 cases that have been 

identified, Dr. Sanchez asked how many have been treated to prevent progression or how many

have been severe enough that they have required therapy either with this tecovirimat or

cidofovir. 

Dr. Rao indicated that the cases that have occurred in the US have been managed mostly 

through outpatient care. There have been some hospitalizations, but those have been due to 

things like pain control if there is proctitis.

Dr. Petersen shared some additional information on medical countermeasures that have been 

released for treatment. A total of 197 courses of oral tecovirimat have been distributed to a

number of jurisdictions. At this point, a total of 18 patients in 8 jurisdictions have received oral 

tecovirimat. Similar to Dr. Rao’s point, severe cases have not been observed. Some IV 

tecovirimat has been distributed, but no patients have yet received IV tecovirimat. CDC is 

working with its state partners who have received these medical countermeasures in order to 

monitor the outcomes of treatment and vaccine use to help inform the vaccine strategy and 

future clinical consultations.

PUBLIC COMMENTS JUNE 23, 2022

Overview 

The floor was opened for public comment on June 23, 2022 at 2:09 PM ET. Given that many 

more individuals registered to make oral public comments than could be accommodated during 

this meeting, selection was made randomly via a lottery. Dr. Lee provided a gentle reminder that 

the ACIP appreciates diverse viewpoints that are respectful in nature and issue-focused rather 

than comments directed at individuals. The comments made during the meeting are included in 

this document. Members of the public also were invited to submit written public comments to 

ACIP through the Federal eRulemaking Portal under Docket No. CDC-2022-0062. Visit 

http://www.regulations.gov for access to the docket or to submit comments or read background 

documents and comments received.
ACIP Meeting Summary June 22-23, 2022

137

Public Comment

Jonathan Couey, PhD

Gigaohm Biological

Thank you. My name is Jonathan Couey. I have no conflicts of interest. The ethical principle of 

informed consent has been effectively ignored for the duration of the pandemic. The FDA and

the CDC long ago failed to meet their responsibility to ensure informed consent in those healthy 

adults who have been already transfected most egregiously in the health of college students 

and teens for whom there was never an emergency. The CDC and FDA failed again just days 

ago to provide the opportunity for informed consent, this time for parents and children under 5 

who on recommending transfection as safe and effective, after nearly 2 years of calling

transfection by a lipid nanoparticle an investigative vaccine, you have failed to provide informed 

consent by pushing a false equivalence between transfection and traditional live-attenuated and 

recombinant vaccines. You have failed to inform the public that transfection, the expression of a 

viral protein via injection of synthetic RNA is a highly variable and tissue-dependent process that 

we are unsure can provoke meaningful immune memory—the goal of any vaccination. You

have failed to notify the public of the potential for autoimmunity while also failing to look for this 

known downside of this technique. The FDA has no data support recommending transfection

for any healthy human in 2022. After more than 2 years, you have failed to inform the public that 

you know the studies upon which these recommendations are based are woefully

underpowered. In place of informed consent, you have pushed the vague concepts of safe and 

effective until they were devoid of meaning. The studies used to specifically recommend

transfection to the under 5 age group are statistical jokes without clinically meaningful

endpoints. You know immunobridging to non-inferiority is useless. Do your job. Of course, the

CDC, NIH, and NIAD also failed to inform the public that they knew late in 2019 that the virus 

had already several key molecular aspects that indicated both its origin and the many known 

countermeasures that would be expected to work. Instead, they said they knew nothing, they 

could see nothing unusual, and that our immune systems were equally vulnerable, and you ran 

with it. Data from your own presentations demonstrate the vast majority of kids have been

infected, a primary counter indication for the administration of any vaccine before 2020. You are 

pushing products under the guise of a regulatory framework that we know by your actions is

proforma only. You failed to inform the public that you know from studying influenza and other 

viruses that the developing immune system is an impossibly complicated process that involves 

imprinting mechanisms that cannot be reversed. The catalog of molecular immune memories

that protects us for a lifetime is formed through the countless exposures of pathogen in our 

childhood, and you have failed to inform the public that you know that transfection to a 2020 

viral code protein cannot be useful in augmenting this process. You know it will not meaningfully 

protect these children because there’s a planet worth of data informing you of this. It’s biology. 

Please gets some and then please do your job. 

Dr. David Wisemen

Synechion

Thank you, Dr. Lee. CDC’s website asserts the FDA has determined that COVID vaccines are

safe and effective for everyone 6 months and older. It certainly has not. FDA’s guidance 

describes the EUA standard as “may be effective lower than the conventional effectiveness 

standard.” For EUA safety, FDA must determine that maybe benefits outweigh the risks. FDA 

has published its methodology in the journal Vaccine and the VRBPAC meetings for 5- to 11-

year-olds. Why has this analysis been absent in recent VRBPAC deliberations? Well, according 
ACIP Meeting Summary June 22-23, 2022

138

to FDA’s Dr. Fink, Pfizer efficacy estimates are preliminary, imprecise, and potentially unstable.

If FDA does not know the vaccine’s “maybe effectiveness,” how can it calculate benefit over 

risk? The green light to vaccinate millions of children based on 3 Pfizer vaccines and [unclear] is 

stunningly absurd and impugns all related decisions about Moderna. These data also show 

negative VE for Pfizer in some scenarios, also shown in waning by CDC. Moderna provides no 

waning data, but surely must have it as they will be reportedly presenting booster data next 

week. In a paper by Dr. Walensky and colleagues, warnings of waning natural immunity present 

a risk to vulnerable populations apply equally to vaccination. Moderna’s 2-dose data for 6 and 

above were pre-Omicron, a problem FDA invoked [unclear] EUA. Why not here? FDA’s Dr. Fink 

tells us that immunobridging may not be scientifically established. Worst still, it targets Wuhan.

Pfizer and Moderna [unclear] are unvalidated with data FDA states they have not verified.

Claims of clinical relevance are ridiculed by CDC’s analysis Friday of 2 Pfizer doses showing 

significant VE to toddlers with failed immunobridging, but the reverse to infants. VSD’s 

myocarditis rates are 6 times higher in 5 to 11-year-olds [unclear]. Dr. Long appropriately notes 

that myocarditis booster rates match or exceed the primary series rates. A new disclosure

reveals that CDC has not [unclear] conducted safety analysis, which we have provided to FDA 

and CDC several times. Confusing intervals, labels, and guidance will surely add to the 1,300+ 

children noted by CDC. VRBPAC’s Dr. Pointer asked Pfizer which cells produce spike, how 

much they produce, and for how long. Pfizer dismissed this question as academic. It is certainly 

not. Understanding these basic questions is vital to understand safety. Moderna’s answer to Dr. 

Sanchez’s similar question today was that the spike persists for less than a week. The Stanford 

study [unclear] showed persistence of vaccine message and antigen for at least 60 days.

Unless FDA, Moderna, CDC, and Pfizer can provide this information, parents have every reason 

to avoid injecting their children with these “may be effective” therapies. Thank you very much.

Mrs. Melissa Chios

AMHFC

Good afternoon. Melissa Chios here to speak on Moderna COVID-19 shots vote for kids aged 6 

to 17 years. I’m hoping that prior to the vote, Dr. Sara Oliver, who is up next, can address the 

many dangerous datapoints emerging over which tenured medical professionals all over the 

world are sounding the alarm, some of whom are the most published in their field. Let me be 

clear. Children’s death rate from COVID-19 is statistically zero with a survival rate of 99.98%. 

Dr. Eric Rubin, CDC advisory committee member, has acknowledged, and I quote, “We’re never 

going to learn about how safe the vaccine is until we start getting it. That’s the way it goes.” If 

our children have a statistical risk of zero from dying from COVID, why on Earth are we to 

assume a risk with a vaccine for which we have no real risk profile? These trials will not be 

concluded until 2024, meaning our children are the experiments. During Tuesday’s VRBPAC 

meeting, Dr. Ruth Link-Gelles from CDC admitted that the COVID-19 shot had negative 

efficacy. One of the already known and acknowledged CDC, I’m sorry, COVID-19 shot risks 

includes myocarditis. Even Dr. Tom Shimabukuro here has previously acknowledged that these 

shots caused myocarditis, citing his own slides, and those of John [unclear] and Nicola Klein. 

Why are so many healthy children and young adults developing myocarditis? Why are so many 

athletes dropping on the ball field? And why is this panel making recommendations in favor of 

[unclear]. You acknowledged it caused severe adverse reactions. Why is no one here 

discussing the serious issue of antibody-dependent enhancement, and prion disease, and 

cancer? Why are 236 records of the 270 pregnant women disappeared from the Pfizer trial, and 

why did 28 of those 34 women whose records remained lose their babies? At Rambam Hospital 

in Haifa, Israel, reports indicate 34% more spontaneous abortions and stillbirths occurred in 

vaccinated women compared to those unvaccinated. This presents a statistically significant 

increase in fetal demise. Why is this all being ignored? Various studies have now confirmed 
ACIP Meeting Summary June 22-23, 2022

139

menstrual dysregulation in women who’ve had the COVID-19 shot as well as heavy spike 

protein accumulation in the ovaries. Studies have also found that these shots affect male 

fertility. Among semen donors, studies show that those vaccinated for COVID-19 have been 

impaired semen concentration and reduced total motile counts. How can anyone ignore these 

signals of infertility, and how can you have another answer or a plan for those who plan to 

procreate in the future? How is it not gross negligence for this panel to continually ignore blatant 

cries of tens of thousands of researchers and doctors across the globe while these alarming 

signals remained unaddressed? Do not turn the other way and vote for another unproven shot 

while these alarming datapoints exist. Doctors, scientists, and parents are watching, and we 

deserve answers. I don’t know how any of the panel can sleep at night knowing that there are 

so many dangerous signals that are being blatantly ignored, and it is unconscionable to 

continue to keep voting for additional vaccines. Has anyone looked at the VAERS reports? By 

the way, 85% of those VAERS reports are reported by healthcare professionals—not the 

general public.

Mrs. Barbara Loeppke

Loeppke Professional Services

Thank you. My name is Barbara Loeppke. I have no conflicts of interest. Regarding the

presentation about the HPV vaccine yesterday, it is concerning that the word “estimated” was 

used over and over and over. Do we not have any real data? There was no mention about the 

adverse events that are experienced by some here—the infertility, the gastroparesis, and the 

other neurological problems. And frankly, I’m really appalled that no one in the committee even 

batted an eye about the studies use for yesterday’s HPV presentation, that they were all 

conducted in third world communities. The reference to the India trials was stopped by their 

government and was quickly brushed over and not discussed. All there was just a general

applause for the vaccine and what it’s done, but no real data. On to the COVID vaccine. The 

use of the phrase, “putting the incidence in context” is definitely bypassing the “first do no harm” 

ethics which used to be part of medicine. Harm of children is now acceptable for the greater

good. If we know that myocarditis can be caused by the vaccine, why is there only one entry 

that’s been determined to be compensable by the countermeasures program? There’s no help 

for the injured. Today, finally, Dr. Shimabukuro had admitted that there are many experiencing 

injuries. He has admitted that they don’t know the mechanism or how to help them. Continuing 

to put these harmful vaccines onto the schedule when you know people are being injured—

these injuries and the lives affected are on your hands. There’s no other answer. With the

official acknowledgement today, you can’t say you don’t know about them, but there have 

already been 2,176,799 reports filed in VAERS for the COVID vaccine. Last week, the 

committee said that putting the COVID vaccine on the schedule just means that parents who 

want the vaccine for their children can get it. However, we all know that if a vaccine is 

recommended for children by the CDC, it will be made mandatory for daycare and school. As 

several states only have a medical exemption, and doctors that give medical exemptions in 

those states are having those medical licenses attacked for doing so, there will be no choice 

allowed for many parents. The decision took away choice. Regarding the allowance of the use 

of the 10-dose vial for babies and toddlers, it is just a disaster waiting to happen. As quoted 

from a renowned statistician,”10-dose vials are terrible because administration errors go up and 

because it’s impossible to guarantee consistency across doses.” Different cap colors have not 

stopped errors. Currently, there are 21,012 dosage errors in VAERS. President Biden on June 

10th stated that parents could make appointments for . . . time expired.
ACIP Meeting Summary June 22-23, 2022

140

Thair Phillips

Seniors Speak Out

Thank you for having me. I’m Thair Phillips of Seniors Speak Out. I want to start by thanking this 

committee for your continued diligence toward ensuring vaccines are available for Americans 

throughout our lifespan. As many of us are parents, grandparents, aunts, and uncles, we were 

particularly grateful for the recent approval of the vaccines for the youngest children. As you

know, older Americans can benefit greatly from vaccines as we are most likely to be managing 

chronic conditions and a weakening immune system. As we learned early on in the pandemic, 

COVID-19 posed a greater threat to older Americans than in any other age group. In fact, grim 

statistics recently released by the Associated Press showed that 3 out of 4 COVID deaths were 

older Americans, which further illustrated this very real threat. Despite entering into year 3 of 

this pandemic, our generation has not lost our resolve in fighting back against this violence and 

has embraced the vaccine more than any other age group, with 95% of Americans over 65 

having received at least 1 dose. With that in mind, it is particularly important to those of us who 

serve older Americans to continue our work to keep their vaccination rates high and for COVID, 

added booster doses if necessary. Now that we as a country are able to vaccinate to prevent 

COVID from the very young to the very old, we should remain steadfast in our efforts to keep 

COVID boosters at the front of older Americans’ minds. To that end, the work of ACIP will be 

critically important in the months to come so that groups like ours can help encourage our fellow 

Americans to remain up-to-date on boosters as well as being vaccinated for other respiratory 

illnesses like the flu and pneumonia. As you know, vaccination rates pre-pandemic were not 

ideal. The pandemic squashed those routine vaccination numbers even further. COVID 

vaccinations were somewhat of a bright spot, with older Americans lining up. Let’s build on that. 

Let’s continue to work together to benefit this important community and ensure that they are 

informed, and most importantly, protected against COVID-19 and other preventable diseases.

Thank you.

Daniel Grenier

Citizen of the United States of America

The authorization of this experimental mRNA gene therapy will forever be a dark moment in 

human history where kids became sacrificial lambs for pharmaceutical profits. Don’t take my 

word for it. Read the BioNTech SEC filing where it says “our revenue heavily depends

on COVID-19 vaccine sales.” The CDC frequently parrots “the benefits outweigh the risks.”

Is that so? The only benefit I can see is 50 billion in expected sales for Pfizer and Moderna in 

2022, and the only risk I see are 1,291 side effects from Pfizer’s documents that the company,

in collusion with the FDA, attempted to hide from us for 75 years. These are the side effects that 

this advisory panel has placed babies as young as 6 months old at risk of. Since these shots do 

not prevent transmission, they are in fact useless and make the public more at risk of COVID. In 

the words of virologist Geert Vanden Bossche, scientifically, there is no rationale whatsoever to 

vaccinate children. There is no added value, only major concerns and major risk, and it is 

criminal. It is especially criminal since children have a 99.995% recovery rate and over 75%

of American children have already built superior natural immunity. In short, this agency has 

faked an emergency for children to gain emergency use authorization to shield itself and the 

pharmaceutical companies from liability for serious and permanent injuries and death. The 1986 

National Childhood Vaccine Injury Act has given rise to a criminal enterprise that allows 

pharmaceutical companies to kill and maim with their shots. It’s especially disturbing that the 

United States of America is the only country in the world conducting this medical experiment on 

children under 5. Countries like Sweden and Finland, for instance, have banned the shot from 

Moderna for under 30 years of age and other younger populations, citing the risk of heart 
ACIP Meeting Summary June 22-23, 2022

141

inflammation that CDC itself recognizes. But even in the [unclear] it’s explicitly stated in the 1.3 

million adverse in the VAERS database including 48,500 in children as of May 20th this year. In 

summary, there is absolutely zero health benefits from these mRNA gene therapies. Preliminary 

data from these shots show that they cannot even meet a 6% efficacy to meet EUA approval. In 

short, I urge every parent to keeping the poisonous shots away from your children and do not 

sacrifice them to the altar of science where the S is a dollar sign. Thank you.

CLOSING REMARKS

Dr. Lee expressed gratitude for these timely updates and emphasized that based on the 

discussion, there is going to be a lot of interest in this particular topic going forward. As the 

meeting was coming to a close, she thanked everyone for all of their work over the past week. 

She said that she was feeling pretty exhausted and thought everyone else must be feeling the 

same way. ACIP had 4 days of meetings in the last 7 days, including a Saturday in a week that 

was inclusive of Father’s Day and Juneteenth so that the committee could provide timely and 

transparent information to the public about vaccines and the decision-making process. She 

stressed that she and Dr. Wharton were extremely grateful for everyone’s extra time and 

willingness to go above and beyond in their service to the public.

Dr. Wharton echoed Dr. Lee’s appreciation to the committee, ex officios, liaisons, presenters, 

and members of the public who were listening in.
ACIP Meeting Summary June 22-23, 2022

142

CERTIFICATION

Upon reviewing the foregoing version of the June 22-23, 2022 ACIP meeting minutes, Dr. Grace 

Lee, ACIP Chair, certified that to the best of her knowledge, they are accurate and complete.

Her original, signed certification is on file with the Management Analysis and Services Office 

(MASO) of CDC.
ACIP Meeting Summary June 22-23, 2022

143

ACIP MEMBERSHIP ROSTER 

CHAIR 

LEE, Grace M, MD, MPH 

Associate Chief Medical Officer for Practice Innovation 

Lucile Packard Children’s Hospital 

Professor of Pediatrics, Stanford University School of Medicine 

Stanford, CA 

Term: 8/4/2021 – 6/30/2023

EXECUTIVE SECRETARY 

WHARTON, Melinda, MD, MPH

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention

Atlanta, GA

MEMBERS 

AULT, Kevin A, MD, FACOG, FIDSA 

Professor and Division Director 

Department of Obstetrics and Gynecology University of 

Kansas Medical Center 

Kansas City, KS 

Term: 10/26/2018 – 6/30/2022 

 

BAHTA, Lynn, RN, MPH, CPH 

Immunization Program Clinical Consultant 

Infectious Disease, Epidemiology, Prevention & Control Division 

Minnesota Department of Health 

Saint Paul, Minnesota 

Term: 7/1/2019 – 6/30/2023

 

BELL, Beth P, MD, MPH 

Clinical Professor 

Department of Global Health, School of Public Health 

University of Washington 

Seattle, WA 

Term: 7/1/2019 – 6/30/2023 

BROOKS, Oliver, MD, FAAP

Chief Medical Officer

Watts HealthCare Corporation

Los Angeles, CA

Past President, National Medical Association

Term: 7/26/2021 – 6/30/2025
ACIP Meeting Summary June 22-23, 2022

144

CHEN, Wilbur H, MD, MS, FACP, FIDSA 

Professor of Medicine 

Center for Vaccine Development and Global Health 

University of Maryland School of Medicine 

Baltimore, MD 

Term: 12/23/2020 – 6/30/2024 

CINEAS, Sybil, MD, FAAP, FACP

Associate Professor of Medicine, Pediatrics, and Medical Science (Clinical)

The Warren Alpert Medical School of Brown University

Associate Program Director

Brown Combined Residency in Internal Medicine and Pediatrics

Providence, RI

Term: 7/28/2021 – 6/30/2025

DALEY, Matthew F, MD 

Senior Investigator 

Institute for Health Research, Kaiser Permanente Colorado 

Associate Professor of Pediatrics 

University of Colorado School of Medicine 

Aurora, CO 

Term: 1/4/2021 – 6/30/2024 

KOTTON, Camille Nelson, MD, FIDSA, FAST 

Clinical Director, Transplant and Immunocompromised Host Infectious Diseases 

Infectious Diseases Division, Massachusetts General Hospital 

Associate Professor of Medicine, Harvard Medical School 

Boston, MA 

Term: 12/23/2020 – 6/30/2024 

LOEHR, Jamie, MD, FAAFP

Owner, Cayuga Family Medicine

Ithaca, New York

Term: 7/26/2021 – 6/30/2025

LONG, Sarah S, MD 

Professor of Pediatrics 

Drexel University College of Medicine 

Section of Infectious Diseases 

St. Christopher’s Hospital for Children 

Philadelphia, Pennsylvania 

Term: 12/24/2020 – 6/30/2024 

MCNALLY, Veronica V, JD 

President and CEO Franny 

Strong Foundation 

West Bloomfield, Michigan 

Term: 10/31/2018 – 6/30/2022 
ACIP Meeting Summary June 22-23, 2022

145

POEHLING, Katherine A, MD, MPH 

Professor of Pediatrics and Epidemiology and Prevention 

Director, Pediatric Population Health 

Department of Pediatrics 

Wake Forest School of Medicine 

Winston-Salem, NC 

Term: 7/1/2019 – 6/30/2023 

 

SÁNCHEZ, Pablo J, MD 

Professor of Pediatrics 

The Ohio State University – Nationwide Children’s Hospital 

Divisions of Neonatal-Perinatal Medicine and Pediatric Infectious Diseases 

Director, Clinical & Translational Research (Neonatology) 

Center for Perinatal Research 

The Research Institute at Nationwide Children's Hospital Columbus, Ohio 

Term: 7/1/2019 – 6/30/2023 

TALBOT, Helen Keipp, MD 

Associate Professor of Medicine 

Vanderbilt University 

Nashville, TN 

Term: 10/29/2018 – 6/30/2022 

EX OFFICIO MEMBERS 

 

Centers for Medicare and Medicaid Services (CMS) 

HANCE, Mary Beth 

Senior Policy Advisor 

Division of Quality, Evaluations and Health Outcomes 

Children and Adults Health Programs Group 

Center for Medicaid, CHIP and Survey & Certification Centers 

for Medicare and Medicaid Services 

Baltimore, MD 

Food and Drug Administration (FDA) 

FINK, Doran, MD, PhD 

Deputy Director, Clinical, Division of Vaccines and Related Products Applications 

Office of Vaccines Research and Review 

Center for Biologics Evaluation and Research 

Food and Drug Administration 

Silver Spring, MD 

 

Health Resources and Services Administration (HRSA) 

RUBIN, Mary, MD 

Chief Medical Officer 

Division of Injury Compensation Programs 

Rockville, MD 

 
ACIP Meeting Summary June 22-23, 2022

146

Indian Health Service (IHS) 

CLARK, Matthew, MD, FAAP, FACP

Physician

Chair, IHS National Pharmacy & Therapeutics Committee

Durango, CO

 

Office of Infectious Disease and HIV/AIDS Policy (OIDP)

KIM, David, MD, MA 

Director, Division of Vaccines, OIDP 

Office of the Assistant Secretary for Health 

Department of Health and Human Services 

Washington, DC 

 

National Institutes of Health (NIH) 

BEIGEL, John, MD 

Associate Director for Clinical Research 

Division of Microbiology and Infectious Diseases 

National Institute of Allergy and Infectious Diseases (NIAID) 

Bethesda, MD 

LIAISON REPRESENTATIVES 

American Academy of Family Physicians (AAFP)

ROCKWELL, Pamela G, DO 

Associate Professor, Department of Family Medicine, University of 

Michigan Medical School 

Medical Director, Dominos Farms Family Medicine 

Ann Arbor, MI 

 

American Academy of Pediatrics (AAP) 

MALDONADO, Yvonne, MD 

Senior Associate Dean for Faculty Development and Diversity 

Professor of Pediatrics and Health Research and Policy 

Chief, Division of Pediatric Infectious Diseases 

Stanford University School of Medicine 

Stanford, CA 

American Academy of Pediatrics (AAP) 

Red Book Editor

KIMBERLIN, David, MD 

Professor of Pediatrics 

Division of Pediatric Infectious Diseases 

The University of Alabama at Birmingham School of Medicine

Birmingham, AL 

 

American Academy of Physician Assistants (AAPA) 

LÉGER, Marie-Michèle, MPH, PA-C 

Senior Director, Clinical and Health Affairs 

American Academy of Physician Assistants 

Alexandria, VA 
ACIP Meeting Summary June 22-23, 2022

147

American College Health Association (ACHA) 

CHAI, Thevy S., MD 

Director of Medical Services 

Campus Health Services 

University of North Carolina at Chapel Hill Chapel Hill, 

NC 

American College Health Association (ACHA) (alternate) 

MCMULLEN, Sharon, RN, MPH, FACHA 

Assistant Vice President of Student & Campus Life for Health and Wellbeing Cornell Health 

Ithaca, NY 

American College of Nurse Midwives (ACNM) 

HAYES, Carol E., CNM, MN, MPH 

Lead Clinician 

Clinical Quality Compliance and Management 

Planned Parenthood Southeast Atlanta, GA 

American College of Nurse Midwives (ACNM) (alternate) 

MEHARRY, Pamela M., PHD, CNM 

Midwifery Educator, Human Resources for Health 

In partnership with University of Rwanda and University of Illinois, Chicago 

American College of Obstetricians and Gynecologists (ACOG) 

ECKERT, Linda O, MD, FACOG 

Professor, Department of Obstetrics & Gynecology 

Adjunct Professor, Department of Global Health 

University of Washington 

Seattle, WA

American College of Physicians (ACP) 

GOLDMAN, Jason M, MD, FACP 

Affiliate Assistant Professor of Clinical Biomedical Science, Florida Atlantic University, Boca 

Raton, Florida 

Private Practice 

Coral Springs, FL 

American Geriatrics Society (AGS) 

SCHMADER, Kenneth, MD 

Professor of Medicine-Geriatrics Geriatrics 

Division Chief 

Duke University and Durham VA Medical Centers 

Durham, NC 

America’s Health Insurance Plans (AHIP) 

GLUCKMAN, Robert A, MD, MACP 

Chief Medical Officer, Providence Health Plans 

Beaverton, OR 
ACIP Meeting Summary June 22-23, 2022

148

American Immunization Registry Association (AIRA) 

COYLE, Rebecca, MSEd 

Executive Director, AIRA

Washington, DC 

American Medical Association (AMA)

FRYHOFER, Sandra Adamson, MD 

Adjunct Associate Professor of Medicine Emory 

University School of Medicine 

Atlanta, GA 

American Nurses Association (ANA) 

RITTLE, Charles (Chad), DNP, MPH, RN Assistant 

Professor, Nursing Faculty 

Chatham University, School of Health Sciences 

Pittsburgh, PA 

American Osteopathic Association (AOA) 

GROGG, Stanley E, DO 

Associate Dean/Professor of Pediatrics 

Oklahoma State University-Center for Health Sciences 

Tulsa, OK 

American Pharmacists Association (APhA) 

HOGUE, Michael D., PharmD, FAPhA, FNAP

Dean and Professor of Loma Linda University School of Pharmacy

Director, Center for Interprofessional Education & Practice

Loma Linda, CA

Association of Immunization Managers (AIM) 

HOWELL, Molly, MPH 

Immunization Program Manager 

North Dakota Department of Health

Bismarck, ND 

Association for Prevention Teaching and Research (APTR) 

ZIMMERMAN, Richard, MD, MPH

Professor

University of Pittsburgh School of Medicine

Department of Family Medicine and Clinical Epidemiology

Pittsburgh, PA

Association of State and Territorial Health Officials (ASTHO) 

SHAH, Nirav D, MD, JD 

Director

Maine Center for Disease Control and Prevention

Augusta, ME 
ACIP Meeting Summary June 22-23, 2022

149

Biotechnology Industry Organization (BIO) 

ARTHUR, Phyllis A, MBA 

Senior Director, Vaccines, Immunotherapeutics and Diagnostics Policy 

Washington, DC 

Council of State and Territorial Epidemiologists (CSTE) 

HAHN, Christine, MD 

State Epidemiologist 

Office of Epidemiology, Food Protection and Immunization Idaho 

Department of Health and Welfare 

Boise, ID 

Council of State and Territorial Epidemiologists (CSTE) (alternate) 

LETT, Susan, MD, MPH 

Medical Director, Immunization Program 

Division of Epidemiology and Immunization 

Massachusetts Department of Public Health 

Boston, MA 

Canadian National Advisory Committee on Immunization (NACI) 

DEEKS, Shelley, MD, MHSc, FRCPC, FAFPHM

Deputy Chief Medical Officer of Health, Department of Health and Wellness, Nova Scotia

Associate Professor, Dalla Lana School of Public Health, University of Toronto

Chair, National Advisory Committee on Immunization

Halifax, Nova Scotia

Infectious Diseases Society of America (IDSA) 

BAKER, Carol J., MD 

Professor of Pediatrics 

Molecular Virology and Microbiology 

Baylor College of Medicine 

Houston, TX 

International Society for Travel Medicine (ISTM) 

BARNETT, Elizabeth D, MD Professor of 

Pediatrics 

Boston University School of Medicine 

Boston, MA 

National Association of County and City Health Officials (NACCHO)

ZAHN, Matthew, MD 

Medical Director, Epidemiology 

Orange County Health Care Agency 

Santa Ana, CA 
ACIP Meeting Summary June 22-23, 2022

150

National Association of County and City Health Officials (NACCHO) (alternate)

DUCHIN, Jeffrey, MD 

Health Officer and Chief, Communicable Disease

Epidemiology and Immunization Section 

Public Health - Seattle and King County 

Professor in Medicine 

Division of Allergy and Infectious Diseases 

University of Washington School of Medicine and School of Public Health

Seattle, WA 

National Association of Pediatric Nurse Practitioners (NAPNAP) 

STINCHFIELD, Patricia A, RN, MS, CPNP 

Director 

Infectious Disease/Immunology/Infection Control

Children's Hospitals and Clinics of Minnesota 

St. Paul, MN 

National Foundation for Infectious Diseases (NFID) 

SCHAFFNER, William, MD 

Chairman, Department of Preventive Medicine 

Vanderbilt University School of Medicine 

Nashville, TN 

National Foundation for Infectious Diseases (NFID) (alternate)

DALTON, Marla, PE, CAE 

Executive Director & CEO 

National Foundation for Infectious Diseases (NFID) 

Bethesda, MD 

National Medical Association (NMA) 

WHITLEY-WILLIAMS, Patricia, MD Professor and Chair 

University of Medicine and Dentistry of New Jersey Robert Wood 

Johnson Medical School 

New Brunswick, NJ 

Pediatric Infectious Diseases Society (PIDS) 

O’LEARY, Sean, MD, MPH 

Associate Professor of Pediatrics 

Pediatric Infectious Diseases 

General Academic Pediatrics 

Children’s Hospital Colorado 

University of Colorado School of Medicine 

Pediatric Infectious Diseases Society (PIDS) (alternate)

SAWYER, Mark H, MD 

Professor of Clinical Pediatrics 

University of California, San Diego School of Medicine 

San Diego, CA
ACIP Meeting Summary June 22-23, 2022

151

Pharmaceutical Research and Manufacturers of America (PhRMA) 

ROBERTSON, Corey, MD, MPH 

Senior Director, US Medical, Sanofi Pasteur 

Swiftwater, PA 

Society for Adolescent Health and Medicine (SAHM) 

MIDDLEMAN, Amy B, MD, MSEd, MPH 

Professor of Pediatrics 

Chief, Section of Adolescent Medicine 

University of Oklahoma Health Sciences Center

Oklahoma City, OK 

Society for Healthcare Epidemiology of America (SHEA)

DREES, Marci, MD, MS 

Chief Infection Prevention Officer & Hospital Epidemiologist 

ChristianaCare 

Wilmington, DE 

Associate Professor of Medicine 

Sidney Kimmel Medical College at Thomas Jefferson University Philadelphia, PA
ACIP Meeting Summary June 22-23, 2022

152

ACRONYMS USED IN THIS DOCUMENT

AAFP American Academy of Family Physicians 

AAP American Academy of Pediatrics

ABCs Active Bacterial Core Surveillance 

ACHA American College Health Association 

ACIP Advisory Committee on Immunization Practices

ACOG American College of Obstetricians and Gynecologists

ACP American College of Physicians 

aIIV Adjuvanted Influenza Vaccine 

AE Adverse Event

AESI Adverse Event of Special Interest 

AHIP America’s Health Insurance Plans

AI/AN American Indian/Alaskan Native 

AIDS Acquired Immunodeficiency Syndrome 

AIM Association of Immunization Managers 

AIRA American Immunization Registry Association 

AMA American Medical Association

AOA American Osteopathic Association 

AOM Acute Otitis Media 

APhA American Pharmacists Association 

AR Adverse Reaction 

ARI Acute Respiratory Illness 

ASTHO Association of State and Territorial Health Officers 

BLA Biologics License Application 

CBER Center for Biologics Evaluation and Research 

CDC Centers for Disease Control and Prevention

CHD Congenital Heart Disease 

CICP Countermeasures Injury Compensation Program 

CLD Chronic Lung Disease 

CMI Cell-Mediated Immunity

CMS Center for Medicare and Medicaid Services

CMV Cytomegalovirus 

COD Cause of Death

COI Conflict of Interest 

CSF Cerebrospinal Fluid 

CSTE Council of State and Territorial Epidemiologists 

CVD Cardiovascular Disease 

CVT Costa Rica Vaccine Trial 

DC District of Columbia

DFO Designated Federal Official

DHDD Division of Human Development and Disability 

DICP Division of Injury Compensation Program 

DoD Department of Defense

DoRIS Dose Reduction Immunobridging & Safety Study 

DRN Distributed Research Network 

DSMB Data Safety Monitoring Board 
ACIP Meeting Summary June 22-23, 2022

153

DVA Department of Veterans Affairs

ED Emergency Department

EMA European Medicines Agency 

EMR Electronic Medical Record 

EPIC Etiology of Pneumonia in the Community Study 

ESRD End-Stage Renal Disease 

ET Eastern Time

EtR Evidence to Recommendation 

EUA Emergency Use Authorization 

EUI Emergency Use Instructions 

eVRC Electronic Vaccination Report Card 

FDA Food and Drug Administration

FRN Federal Register Notice 

FY Fiscal Year

GBS Guillain-Barré Syndrome 

GI Gastrointestinal 

GMR Geometric Mean Ratio 

GMT Geometric Mean Titers 

GRADE Grading of Recommendation Assessment, Development and Evaluation 

HCP Healthcare Personnel / Providers

HCT Hemolytic Cell Transplant 

HSCT Hematopoietic Stem Cell Transplant 

HD-IV High-Dose Influenza Vaccine 

HHS (Department of) Health and Human Services

HIV Human Immunodeficiency Virus

HPV Human Papillomavirus

HRSA Health Resources and Services Administration 

HSCT Hematopoietic Stem Cell Transplant 

HVTN HIV Vaccine Trials Network 

HA Hemagglutinin 

IARC International Agency for Research on Cancer

IAVG Interagency Vaccine Group 

ICU Intensive Care Unit

IDSA Infectious Disease Society of America 

IHR International Health Regulation Emergency Committee

IHS Indian Health Service 

IIS Immunization Information System 

ILI Influenza-Like Illness 

IND Investigational New Drug 

IPD Invasive Pneumococcal Disease 

ISD Immunization Services Division 

ISO Immunization Safety Office 

ISS Integrated Safety Summary in Infants 

ITP Immune Thrombocytopenic Purpura 

IV Intravenous

J&J Johnson & Johnson

kbp Kilobase 

KEN SHE KENya Single-dose HPV-vaccine Efficacy Study

KFF Kaiser Family Foundation 
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LRN Laboratory Response Network 

LTCF Long-Term Care Facility 

MAC Multi-Age Cohort 

MAAE Medically Attended Adverse Event 

MCV Meningococcal Vaccine 

MIS-C Multisystem Inflammatory Syndrome in Children 

MMR Measles, Mumps, Rubella 

MMSC Male-to-Male Sexual Contact 

MMWR Morbidity and Mortality Weekly Report

MSA Metropolitan Statistical Area 

MSM Men who have Sex with Men 

MVA-BN Modified Vaccinia Ankara-Bavarian Nordic 

NACCHO National Association of County and City Health Officials 

NACI National Advisory Committee on Immunization Canada

NAPNAP National Association of Pediatric Nurse Practitioners 

NBP Non-Bactearemic Pneumonia 

NCBDDD National Center on Birth Defects and Developmental Disabilities 

NCEZID National Center for Emerging and Zoonotic Infectious Diseases 

NCHS National Center of Health Statistics 

NCIRD National Center for Immunization and Respiratory Diseases 

NEJM New England Journal of Medicine 

NFID National Foundation for Infectious Diseases 

NHSN National Healthcare Safety Network 

NIAID National Institute of Allergy and Infectious Diseases 

NIH National Institutes of Health

NIS-CCM National Immunization Survey Child COVID-19 Module 

NIS-Teen National Immunization Survey-Teen 

NMA National Medical Association 

NREVSS National Respiratory and Enteric Virus Surveillance System 

NP Nasopharyngeal Swab 

NVAC National Vaccine Advisory Committee 

NVPO National Vaccine Program Office 

NVSN New Vaccine Surveillance Network 

OASH Office of the Assistant Secretary for Health 

ODPHP Office of Disease Prevention and Health Promotion 

OIDP Office of Infectious Disease and HIV/AIDS Policy

OPV Oral Polio Vaccine 

PASC Post-Acute Sequelae of SARS-CoV-2 

PCP Primary Care Provider/Practitioner

PCR Polymerase Chain Reaction

PEP Post-Exposure Prophylaxis

PHAC Public Health Agency Canada 

PHEIC Public Health Emergency of International Concern 

PICO Population, Intervention, Comparison, Outcomes

PIDS Pediatric Infectious Disease Society 

PPE Personal Protective Equipment 

PrEP Pre-Exposure Prophylaxis

QALY Quality-Adjusted Life Year 

RCA Rapid Cycle Analysis
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RCT Randomized Controlled Trial

RIV Recombinant Influenza Vaccine 

RN Registered Nurse

RNA Ribonucleic Acid 

RR Relative Risk

RSV Respiratory Syncytial Virus 

RT-PCR Reverse Transcriptase Polymerase Chain Reaction

RVE Relative Vaccine Efficacy 

SAE Serious Adverse Event 

SAGE Strategic Advisory Group of Experts on Immunization 

SAHM Society for Adolescent Health and Medicine 

sBLA Supplemental Biologics License Application 

SD-IIV Standard-Dose Unadjuvanted Influenza Vaccines 

SHEA Society for Healthcare Epidemiology of America 

SME Subject Matter Expert

SNS Strategic National Stockpile 

STI Sexually Transmitted Infection 

TTS Thrombotic Thrombocytopenia Syndrome 

UK United Kingdom

US United States

USG United States Government

VA (US Department of) Veteran’s Affairs 

VAERS Vaccine Adverse Event Reporting System

VaST WG Vaccine Safety Technical Work Group 

VE Vaccine Efficacy

VE Vaccine Effectiveness

VFA Vaccines for Adults 

VFC Vaccines For Children 

VICP National Vaccine Injury Compensation Program 

VIGIV Vaccinia Immune Globulin Intravenous 

VLP Virus-Like Particle 

VRBPAC Vaccine and Related Blood Products Advisory Committee 

VRC Vaccine Research Center 

VSD Vaccine Safety Datalink

WG Workgroup

WHO World Health Organization