MEETING OF THE ADVISORY 

COMMITTEE ON IMMUNIZATION 

PRACTICES (ACIP)

FEBRUARY 23-24, 2022

SUMMARY MINUTES

TABLE OF CONTENTS

MEETING PURPOSE ................................................................................................................................... 3

THURSDAY: FEBRUARY 23, 2022.............................................................................................................. 3

WELCOME AND INTRODUCTIONS......................................................................................... 3

Call to Order/Roll Call ............................................................................................................ 3

Announcements..................................................................................................................... 3

TICKBORNE ENEPHALITIS (TBE) VACCINE.......................................................................... 4

Session Introduction .............................................................................................................. 4

Review of Considerations for Use of TBE Vaccine in Travelers and Laboratorians.............. 4

Discussion Summary ............................................................................................................. 9

Vote #1: TBE Vaccine for Laboratory Workers....................................................................10

Vote #2: TBE Vaccine for Persons Moving Abroad or Traveling to a TBE-Endemic Area ..10

Vote #3: TBE Vaccine for Persons without Extensive Tick Exposure Moving or Traveling to 

a TBE-Endemic Area Based on an Assessment of Additional Risk Factors........................11

CHOLERA VACCINE ..............................................................................................................13

Session Introduction ............................................................................................................13

Clinical Considerations for Use of Cholera Vaccine in Children and Adolescents 2–17 Years 

of Age ..................................................................................................................................13

Discussion Summary ...........................................................................................................16

Vote: Cholera Vaccine Recommendation............................................................................18

INFLUENZA VACCINE............................................................................................................19

Session Introduction ............................................................................................................19

Influenza Activity Update .....................................................................................................19

Discussion Summary ...........................................................................................................20

Recommending Enhanced Seasonal Influenza Vaccines in Adults ≥65 Years of Age: 

Potential Impacts on Influenza Burden ................................................................................20

Discussion Summary ...........................................................................................................23

Influenza Vaccines for Older Adults.....................................................................................24

Discussion Summary ...........................................................................................................28

HEPATITIS VACCINE .............................................................................................................29
ACIP Meeting Summary February 23-24, 2022 

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Session Introduction ............................................................................................................29

PreHevbrio for Adult HepB Vaccination: EtR and GRADE..................................................29

Discussion Summary ...........................................................................................................31

MEASLES, MUMPS, RUBELLA (MMR) VACCINE WORKGROUP........................................32

Session Introduction ............................................................................................................32

MMR Safety and Immunogenicity........................................................................................33

Discussion Summary ...........................................................................................................36

PUBLIC COMMENT ................................................................................................................38

Overview..............................................................................................................................38

Public Comment ..................................................................................................................39

THURSDAY: FEBRUARY 24, 2022............................................................................................................43

AGENCY UPDATES................................................................................................................43

Centers for Disease Control and Prevention .......................................................................43

Centers for Medicare and Medicaid.....................................................................................44

Food and Drug Administration .............................................................................................45

Health Resources and Services Administration...................................................................45

Indian Health Services.........................................................................................................45

National Institutes of Health................................................................................................. 46

Office of Infectious Disease and HIV/AIDS Policy ...............................................................47

PNEUMOCOCCAL VACCINES...............................................................................................47

Session Introduction ............................................................................................................47

Epidemiology of Pneumococcal Disease and Pneumococcal Vaccine Coverage in US 

Children ...............................................................................................................................49

Discussion Summary ...........................................................................................................52

PCV15 Phase 2/3 Study Results in Children.......................................................................53

Discussion Summary ...........................................................................................................56

GRADE and EtR for PCV15 Use in US Children................................................................. 58

Discussion Summary ...........................................................................................................62

Summary and Next Steps....................................................................................................63

Discussion Summary ...........................................................................................................64

CERTIFICATION.........................................................................................................................................66

ACIP MEMBERSHIP ROSTER...................................................................................................................67

ACRONYMS USED IN THIS DOCUMENT................................................................................................. 76
ACIP Meeting Summary February 23-24, 2022 

3 

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 February 23, 2022. The meeting took place remotely via 

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

which focused on tickborne encephalitis (TBE), cholera, influenza, hepatitis, and pneumococcal 

vaccines; establishment of a Measles, Mumps, Rubella (MMR) Vaccine Workgroup (WG); 

agency updates; and public comments. 

THURSDAY: FEBRUARY 23, 2022

WELCOME AND INTRODUCTIONS

Call to Order/Roll Call

Dr. Grace Lee (ACIP Chair) called to order and presided over the February 23-24, 2022 ACIP 

meeting. Dr. Lee 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 conflict of interest (COIs) was declared: 

 Dr. Chen reported that his employing institution, the University of Maryland, received a grant 

from Emergent BioSolutions that supported work he conducted to develop a Shigella 

vaccine. Given that this constituted a COI on decisions regarding the cholera vaccine

recommendations and discussions during this meeting, he indicated that he would not vote 

on the cholera vaccine.

Announcements

Dr. Melinda Wharton (ACIP Executive Secretary, CDC) 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 an 

oral public comment session prior to the vote at approximately 2:25 PM Eastern Time (ET) on 

February 23, 2022. Given that more individuals registered to make oral public comments than 

could be accommodated, selection was made randomly via a lottery. Those 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-2022-0022. 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 

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.
ACIP Meeting Summary February 23-24, 2022 

4 

Dr. Wharton 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 July 1, 2022, for the 4-year term beginning July 2023.

TICKBORNE ENEPHALITIS (TBE) VACCINE

Session Introduction

Dr. Katherine Poehling (ACIP WG Chair) introduced this session on behalf of the TBE 

Vaccine Workgroup (WG). She explained that in terms of background, the Food and Drug 

Administration (FDA) approved the TBE vaccine TicoVacTM manufactured by Pfizer in August 

2021. Given that no TBE vaccine has been previously licensed in the United States (US), there 

is no existing ACIP TBE vaccine recommendation. As a reminder, the TBE Vaccine WG was 

formed in September 2020 to discuss the use of TBE vaccines in US persons traveling abroad 

and laboratory workers. The TBE Vaccine WG presented to the ACIP in October 2020 on the 

background of TBE disease and vaccines and a summary of Pfizer’s TBE vaccine. In February 

2021, the WG presented TBE epidemiology in endemic areas and TBE among US travelers and 

laboratory workers. In September 2021, the WG presented the immunogenicity and safety of 

Pfizer’s TBE vaccine. In January 2022, the WG presented the Evidence to Recommendations 

(EtR) framework. The focus of the February 2022 session was on a brief review of TBE and 

TBE vaccines, review of considerations for use of TBE vaccines and proposed 

recommendations for laboratory workers, and review of considerations for use of TBE vaccines 

and proposed recommendations for persons who travel abroad.

Review of Considerations for Use of TBE Vaccine in Travelers and Laboratorians

Dr. Susan Hills (CDC/NCEZID) reminded everyone that following presentation of the Evidence 

to Recommendations (EtR) Frameworks for TBE vaccine during a recent ACIP meeting, the 

TBE Vaccine WG discussed its recommendations in light of ACIP members’ feedback. In 

particular, the WG focused on the categories of “Recommended” and “Shared Clinical DecisionMaking” in the context of travel vaccines and providing the best clarity regarding who might 

benefit from vaccination, given that this vaccine is more likely to be administered by general 

healthcare providers rather than specialist or travel medicine providers. During this session, she 

presented the WG’s revised recommendations for ACIP members’ consideration, pointing out 

that ACIP would be asked for separate votes on recommendations for the following: 1) 

Laboratory Workers; 2) Persons Who Travel Abroad (Recommended component); and 3) 

Persons Who Travel Abroad (Shared Clinical Decision-Making component).

After the previous meeting, members of the 2 ACIP WGs with proposed travel vaccine 

recommendations discussed categories with the ACIP Secretariat and received the following 

guidance about each component:

 Recommended:

− Vaccine should be recommended if there is any group of people who should receive 

the vaccine (i.e., the benefits of receiving the vaccine clearly outweigh the risks*)
ACIP Meeting Summary February 23-24, 2022 

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 Shared Clinical Decision-Making:

− No group for whom the vaccine should be recommended can be identified, but some 

individuals might reasonably choose vaccination and some providers might 

reasonably wish to recommend it for some travelers OR

− There are any groups of people where the benefits of receiving the vaccine might not 

outweigh the risks* or there is uncertainty

 Note on Shared Clinical Decision-Making

− Travel vaccines often require consultation with a healthcare provider (HCP) to 

identify which, if any, are indicated based on the traveler’s age; travel plans, 

including destinations, duration, and activities; and other risk factors. This is not 

shared clinical decision-making

*Risk-benefit consideration for vaccination should weigh factors such as the likelihood of exposure (based on location, season, time, 

and activities), risk of disease and its potential severity, vaccine efficacy (VE), and possibility of vaccine-associated serious adverse 

events (SAEs). 

Before presenting the considerations that went into developing the proposed TBE vaccine 

recommendations, Dr. Hills provided a brief review of TBE and TBE vaccine. TBE is a flavivirus 

related to Powassan virus. There are 3 main subtypes of TBE virus that differ in their 

geographic distribution and in the severity of the disease they cause. TBE virus is primarily 

transmitted by infected Ixodes species ticks. Infections are usually acquired in wooded

or surrounding areas during recreational activities (e.g., camping, hiking, fishing, or hunting) or 

by persons involved in outdoor occupations (e.g., forestry service, farming). TBE is focally 

endemic in parts of Europe and Asia. Approximately 5,000 to 10,000 TBE cases are reported 

annually from endemic areas. Incidence is variable from country-to-country, in areas within 

countries, and from year-to-year. The main risk period occurs in the warmer months from April

through November when ticks are most active. Among US persons, there have been very low 

numbers of TBE cases, with only 20 cases diagnosed in the 20-year period from 2001-2020. Of 

these, 11 were among civilian travelers and 9 among military personnel. However, when 

neruoinvasive disease occurs, it can have potentially high fatality and sequela rates.

The TBE vaccine manufactured by Pfizer as TicoVacTM was approved by the Food and Drug 

Administration (FDA) in 2021 for use in persons ≥1 year of age. Although only recently licensed 

in the US, the current formulation of the vaccine has been available internationally for more than 

20 years, and more than 75 million doses have been administered. It is currently marketed in 

about 30 countries, primarily in Europe. Based on the GRADE (Grading of Recommendation 

Assessment, Development and Evaluation) assessment conducted by the ACIP TBE Vaccine 

WG, immunogenicity results showed that seropositivity rates after the primary series were high 

at over 95% in most studies, and were also high after a booster dose. One limitation in this 

assessment was that the vaccine is based on a European subtype TBE virus, and there is likely 

but unconfirmed protection against non-European TBE virus subtypes. In terms of safety, 

vaccine-related SAEs were rarely reported.
ACIP Meeting Summary February 23-24, 2022 

6 

In terms of key considerations for development of recommendations for laboratory workers 

working with TBE virus, several key factors were considered by the WG. First, TBE virus 

transmission has been documented in the laboratory through virus aerosolization. Transmission 

through accidental percutaneous or mucosal exposures is possible. More than 46 laboratoryacquired TBE virus infections have been reported globally. Fewer than 10 laboratories

in the US currently work with TBE virus for diagnostic or research purposes, meaning that a 

limited number of staff would require vaccination. TBE vaccination will reduce laboratorians’ risk 

of potentially very severe disease. Vaccine implementation is feasible as it likely can be 

implemented through existing occupational health programs. When considering all the domains 

of the EtR Framework for laboratory workers, the WG determined that the desirable 

consequences of vaccination clearly outweigh the undesirable consequences

in most settings and proposed the following recommendation for ACIP consideration:

TBE vaccination is recommended for laboratory workers with a potential for exposure to 

TBE virus.

Regarding the WG’s key considerations and proposed recommendations for persons who travel 

abroad, the WG started by asking whether there is a group of people who should receive the 

vaccine, i.e., for whom the benefits of receiving the vaccine clearly outweigh the risks. Dr. Hills 

discussed each of the following key factors considered by the WG:

 Overall risk of disease

 Potential severity of disease

 Patterns of disease transmission

 Risk factors for disease among US travelers

 Tick-related factors

 Vaccination recommendations in endemic countries

 Vaccine-related factors

In regard to the overall risk of disease for US civilian travelers, TBE is clearly a very rare 

disease with only 11 cases diagnosed during the past 20 years, or about 1 TBE case diagnosed 

every 2 years. Based on numbers of US travelers, the risk for all US travelers to TBE-endemic 

countries is less than 1 TBE case per 30 million trips. To understand risk among a more select 

group of travelers, the WG considered just those travelers who might visit specific risk areas 

within endemic countries, who travel during the main transmission season, and undertake 

activities with risk of tick exposure. In this specific group, the risk estimate was approximately 1 

TBE case per 2 million trips. Because of potential inaccuracies in assumptions required for the 

calculation and possible under-diagnosis of TBE or other factors, the risk range could be from 

0.1-5 cases per million trips.

While TBE case numbers are low, potential severity of illness for patients with neuroinvasive 

disease must be considered. Most persons will require hospitalization and there are no specific 

antiviral treatments. Sequela have been reported in 10% to 50% of persons presenting with 

neurologic disease and can be severe, including permanent physical disabilities or cognitive 

impairment. Case fatality rates ranging from 1% to 20% have been reported. 

The WG considered factors related to the patterns and distribution of disease. There is a 

seasonal risk, with the main risk in the warmer months from April through November when ticks 

are most active. Because TBE is tickborne, large outbreaks do not occur. There is some 

uncertainty in defining risk in specific locations within endemic areas, given that transmission 
ACIP Meeting Summary February 23-24, 2022 

7 

can be variable from year-to-year. Risk areas can be very focal and accurate data often are

unavailable in real-time or, in some countries, at all. 

The risk factors were considered for infection among US civilian travelers, although with only 11 

cases there were limited data to define the epidemiology. The common factors in all cases in 

which itinerary information was available (8 travelers) was that they had had at least 1 

opportunity for exposure to ticks and all traveled during the main TBE virus transmission season 

in Spring or Summer. There was no apparent association with duration of travel, with infected 

persons reporting travel periods from 7 days to 2 months; specific activities, with travelers 

reporting a variety of activities (hiking, camping, fishing, trail running); basic demographics, with 

cases ranging in age from a young child to a male in his 70s; or specific travel locations, with 

cases infected in various places throughout the risk area, including Europe, Russia, and China. 

For particular tick-related factors, it was noted that humans must enter tick habitats and come in 

contact with ticks to have a risk of TBE because unlike mosquitoes, ticks will not search out 

humans. Travelers do not pose a risk for TBE virus establishment in the US and so vaccination 

does not have population-level benefits.

Review of national TBE vaccination recommendations in endemic countries indicates that many 

countries do have recommendations, but their extent varies substantially. One country has a 

universal TBE vaccination recommendation. Some countries have recommendations for 

populations living in specific highly endemic or endemic areas or only for persons at highest risk

such as those in certain outdoor occupations. Some countries have no TBE vaccination policy.

Regarding vaccine-related factors, the vaccine has a very good immunogenicity and safety 

profile, but like any vaccine has the possibility of SAEs. For 2 of the 3 main TBE virus subtypes, 

there is likely but unproven effectiveness of the vaccine. These are the Siberian and Far 

Eastern subtypes that occur in the Eastern part of the TBE-endemic area and that cause more 

severe disease. TBE vaccine will cost more than $250 per dose and will be paid for out of 

pocket by most travelers and there might be opportunity costs if a traveler has to consider 

buying TBE vaccine versus purchasing travel insurance or other vaccines with available 

financial resources.

Noting all these factors, the WG considered whether there was any group of people who should 

receive the vaccine i.e., for whom the benefits of receiving the vaccine clearly would outweigh 

the risks. There was some variability in opinion among the WG members on this question, but 

the following points summarize the WG’s conclusions. Firstly, even for the group of travelers to 

TBE-endemic areas who travel during the transmission season and undertake an outdoor 

activity with risk of tick exposure, the risk for TBE disease is very low with fewer than 1 TBE 

case diagnosed per 1 million travelers. It would be difficult to justify a TBE vaccination 

recommendation for all travelers in this group. However, there is likely to be a smaller group

who are at higher risk. All US traveler cases reported an itinerary in which their activities would 

have put them at risk of tick exposure. It follows that travelers who have the most extensive 

exposure to ticks will have the highest likelihood of TBE virus infection. Thirdly, although TBE is 

a rare disease, it can be very severe, and most travelers who get neurologic disease will require 

hospitalization and will have a risk of sequela and death. Finally, there is a safe and effective 

vaccine. Based on these considerations, the TBE Vaccine WG proposed the following 

recommendation for ACIP consideration: 
ACIP Meeting Summary February 23-24, 2022 

8 

TBE vaccine is recommended for persons who are moving abroad or traveling to a TBEendemic area and will have extensive exposure to ticks based on their planned outdoor 

activities and itinerary.

The WG then discussed the second component for the TBE vaccine recommendations,

considering whether there is an additional group for whom a shared clinical decision-making 

category of recommendation would be appropriate. They discussed whether there are data 

suggesting that there are any groups for whom there is uncertainty in the risk-benefit 

considerations, or circumstances in which some individuals might reasonably choose 

vaccination, or some providers might recommend it for some travelers. The WG discussed 

several important topics including the U.S. traveler TBE cases and their extent of exposure to 

ticks, that there is a higher risk of a poorer medical outcome among some persons, and that 

there is variability in the perception and tolerance of risk among travelers. 

Firstly, given the focus of the primary TBE vaccine recommendation, the WG considered 

whether all US traveler cases have had extensive exposure to ticks. While all US travelers 

reported some exposure, not all might have had what could be considered “extensive” 

exposure, although this was difficult to assess in all cases based on the amount of itinerary 

information available. Nonetheless, to protect all travelers going to TBE-endemic locations who 

might have tick exposure, a very large number of doses would need to be given to prevent 1 

TBE case. The WG estimated that more than 1 million travelers would need to be vaccinated to 

prevent 1 TBE case. Secondly, in regard to higher risk of a poorer medical outcome among 

some persons with TBE, older persons have consistently been shown to have poorer 

outcomes.1 Finally, the WG considered personal perception and tolerance of risk. For the EtR 

assessment, one of the surveys the WG reviewed was on decision-making on vaccination for a 

disease that is similar to TBE with a vaccine that is similar to TBE vaccine i.e., is safe and 

effective, has a similar low probability of SAEs, and costs over $250 per dose. The results 

indicated that 32% of respondents were somewhat or very likely to be vaccinated, 43% were 

somewhat or very unlikely to be vaccinated, and 25% were unsure.2 The risk of a 1 in 1 million 

possibility of a severe outcome was a key factor in decision-making on whether to be vaccinated 

for respondents in both groups, indicating very different personal perceptions and tolerance of 

risk.

Considering these factors, the WG conclusions on an additional share clinical decision-making 

component of the TBE vaccine recommendations were that some travelers might be exposed to 

ticks but will not have extensive exposure, and several factors might be considered in the riskbenefit assessment for TBE vaccination. These include that there is an extremely low risk of 

disease overall, with heterogeneity in risk based on activities and itinerary; some persons might 

have risk factors for a poorer medical outcome; and there are clear differences between 

individuals in their perception and tolerance of risk for a severe disease like encephalitis that 

can cause death or disability. Given that the overall risk-benefit assessment is ill-defined for this 

group of travelers, but that some individuals might reasonably choose vaccination and some 

providers might wish to recommend it, the WG thought that a second shared clinical-decision 

making component for the TBE vaccination recommendations would be appropriate. Based on 

these considerations, the TBE Vaccine WG proposed the following recommendation for ACIP 

consideration: 

1

 Schuler et al, Euro Surveill 2014; Lindquist, Lancet 2008 

2 Hills SL et al. Perceptions among the U.S. population of value of Japanese encephalitis (JE) vaccination for travel to JE-endemic 

countries; Vaccine 2020 
ACIP Meeting Summary February 23-24, 2022 

9 

TBE vaccine might be considered for persons traveling or moving to a TBE-endemic

area who might engage in outdoor activities in areas ticks are likely to be found. The 

decision to vaccinate should be based on an assessment of their planned activities and 

itinerary, risk factors for a poorer medical outcome, and personal perception and 

tolerance of risk.

Discussion Summary

Dr. Long noted that the “might be considered” recommendation was a “proposed 

recommendation” and sounded like it might be applied to the group for whom the vaccine is 

going to be “recommended.”

Dr. Hills clarified that the “proposed recommendation” heading was the second component of 

the overall recommendations and that this was the proposed shared clinical decision-making 

recommendation.

Dr. Sanchez commended the WG for this great follow-up to ACIP’s previous discussions, and 

he agreed with the recommendation and the shared clinical decision-making recommendation.

Dr. Kimberlin (AAP Redbook) observed that typically with a universal recommendation, the 

vaccine should be given. In his experience with shared clinical decision-making, it is “may be 

considered” rather than “ might be considered.” He wondered whether there was any nuance 

between the words “may” and “might” in this proposed recommendation. Other ACIP members 

indicated that they had the same question.

Dr. Hills said she believed CDC has tended to use “might” rather than “may” as “might” implies 

possibility and “may” suggests permission. She indicated that she would confer with the

Secretariat for guidance and to ensure that this was clarified before the vote.

Dr. Daley inquired as to how and where “extensive exposure” would be defined.

Dr. Hills indicated that the WG discussed this and intend to include some text with the 

recommendations. For shorter duration travel, it might mean frequent exposure such as daily 

activities in environments that might harbor infected ticks. For longer travel duration of a month 

or longer, it might mean regular exposure such as a few times a month.

Regarding the question of “may” or “might,” Dr. Goldman expressed concern because his 

understanding of the Affordable Care Act (ACA) was that recommended vaccines must be 

covered by insurers. It was not clear to him how “might consider” and shared clinical decisionmaking play into that as far as the concern for equity, access, and patients being able to afford 

the vaccines. The comment was made earlier that this vaccine probably will be administered in 

general medical offices as opposed to travel clinics. While he has access to certain travel 

vaccines in his practice, the volume of patients presenting for these is so low that it does not 

allow for storing the vaccines cost-effectively. This could lead to a difficulty in access

for patients to get the vaccines except at travel clinics as opposed to general medical offices. He 

asked whether the language could be clarified and how that might play into insurance coverage

under the ACA.

Dr. Hills clarified that the ACA relates to vaccines that are on the routine vaccine schedules. 

Travel vaccines are not included on the routine vaccine immunization schedules. 
ACIP Meeting Summary February 23-24, 2022 

10

Vote #1: TBE Vaccine for Laboratory Workers 

Dr. Susan Hills (CDC/NCEZID) presented proposed recommendation #1 for TBE vaccine as 

follows:

TBE vaccination is recommended for laboratory workers with a potential for exposure to 

TBE virus.

Motion/Vote #1: TBE Vaccine for Laboratory Workers

Dr. Talbot made a motion for ACIP to adopt the recommendation stating that, “TBE vaccination 

is recommended for laboratory workers with a potential for exposure to TBE virus.” 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

Vote #2: TBE Vaccine for Persons Moving Abroad or Traveling to a TBE-Endemic Area 

Dr. Susan Hills (CDC/NCEZID) presented proposed recommendation #2 for TBE vaccine as 

follows:

TBE vaccine is recommended for persons who are moving abroad or traveling to a TBEendemic area and will have extensive exposure to ticks based on their planned outdoor 

activities and itinerary.

Discussion Summary

Dr Long pointed out that “moving abroad” is a large place across an ocean and proposed 

deleting the word “abroad” and instead state, “people who are moving or traveling to an 

endemic area.” She also suggested that the asterisk be included in the recommendation about 

other considerations such as activities and outbreaks.

Dr. Hills shared the additional information that would be included in the Clinical Consideration, 

on the CDC website, and in a box to draw people’s attention to the information. If CDC becomes 

aware of a particular concern regarding an outbreak, the Division of Global Migration and 

Quarantine (DGMQ) would likely be responsible for posting a notice to alert travelers. 
ACIP Meeting Summary February 23-24, 2022 

11

Dr. Poehling reported that the WG engaged in extensive conversations about this in terms of 

figuring out how best to word the recommendation. Their assessment was they preferred the 

wording to focus on the planned activities and itinerary and highlight the main components, 

while providing the details in the Clinical Considerations and they liked the box to draw people’s 

attention to relevant information.

Dr. Lee expressed appreciation for Dr. Long’s editorial eye. She reminded everyone that ACIP 

tries in general to keep recommendations succinct and allow for the details to be provided in the 

Clinical Considerations as long as it does not change the intent of the recommendation.

Dr. Long said she was comfortable with the wording as stated, with the intent of the Clinical 

Considerations capturing the detailed information, considering Dr. Poehling’s additional 

comments, and the fact that no hands were raised by practitioners in the meeting.

With no objections to the clarification, Dr. Lee indicated that the motion would stand but with the 

suggestion to amend the wording slightly for clarity by removing the word “abroad.”

Motion/Vote #2: TBE Vaccine for Persons Moving 

Abroad or Traveling to a TBE-Endemic Area

Dr. Sanchez made a motion for ACIP to adopt the recommendation with the proposed 

amendment stating that, “TBE vaccine is recommended for persons who are moving or traveling 

to a TBE-endemic area and will have extensive exposure to ticks based on their planned 

outdoor activities and itinerary.” Dr. Ault 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 #3: TBE Vaccine for Persons without Extensive Tick Exposure Moving or Traveling 

to a TBE-Endemic Area Based on an Assessment of Additional Risk Factors

Dr. Susan Hills (CDC/NCEZID) presented proposed recommendation #3 for TBE vaccine as 

follows, with the amendment to change “might” to “may”:

TBE vaccine may be considered for persons traveling or moving to a TBE-endemic area 

who might engage in outdoor activities in areas ticks are likely to be found. The decision 

to vaccinate should be based on an assessment of their planned activities and itinerary, 

risk factors for a poorer medical outcome, and personal perception and tolerance of risk.
ACIP Meeting Summary February 23-24, 2022 

12

Motion/Vote #3: TBE Vaccine for Persons without Extensive Tick Exposure Moving or 

Traveling to a TBE-Endemic Area Based on an Assessment of Additional Risk Factors

Ms. Bahta made a motion for ACIP to adopt the recommendation stating that, “TBE vaccine 

may be considered for persons traveling or moving to a TBE-endemic area who might engage in

outdoor activities in areas ticks are likely to be found. The decision to vaccinate should be 

based on an assessment of their planned activities and itinerary, risk factors for a poorer 

medical outcome, and personal perception and tolerance of risk.” Dr. Daley 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:

Dr. Kotton commented that as someone who has practiced travel medicine for over 20 years,

she was very happy about this overall recommendation, the thoughtfulness that went into it, and 

the flexibility it would provide for clinicians practicing travel medicine. 

Dr. Lee commended Drs. Poehling and Hills for their leadership of this WG and recognized the 

effort of the WG that went into considering and addressing the complicated issues involved, and 

the importance of this recommendation. 

Dr. Chen noted that he had the pleasure of serving on the TBE Vaccine WG for more than a 

year during their many discussions. He congratulated and thanked Dr. Poehling for Chairing the 

WG, Dr. Hills for guiding the discussions, and her team for all of their hard work in helping to pull 

all of this together. He commented that even though the burden of TBE is not perceived to be 

large and it might be difficult to implement this vaccine due to the complexity of assessing where 

tick habitats are, tick and mosquito habitats continue to expand and flavivirus circulation 

continues to increase with the trends of global warning. This is a reminder that because 

flaviviruses, such as West Nile Virus (WNV) and Yellow Fever (YF), continue to scourge the

world, these types of vaccines will become increasingly important.
ACIP Meeting Summary February 23-24, 2022 

13

CHOLERA VACCINE

Session Introduction

Dr. Pablo Sanchez (ACIP WG Chair) introduced this session on behalf of the Cholera Vaccine 

WG, indicating that the policy topic under consideration by the WG for which there would be a 

vote was, “Should ACIP recommend CVD103-HgR for children and adolescents aged 2-17 

years traveling to an area with active cholera transmission?” In June 2016, ACIP recommended 

cholera vaccine for adult travelers 18-64 years of age traveling from the United States to an 

area with active choleric transmission. In December 2020, FDA extended the approved usage

to include children and adolescents 2-17 years of age. In February 2021, the WG presented 

background information and the manufacturer presented pediatric clinical trial data. In January 

2022, the WG presented the EtR Framework and the manufacturer presented data on pediatric 

dose development. This session focused on the presentation of evidence, recommendation 

summary, considerations for use, and proposed policy options for the cholera vaccine among 

children and adolescents 2-17 years of age.

Clinical Considerations for Use of Cholera Vaccine in Children and Adolescents 2–17 

Years of Age

Dr. Jennifer Collins (CDC/NCEZID) pointed out that the PICO (population, intervention, 

comparison, outcomes) components related to the policy question include the population of 

children and adolescents aged 2-17 years traveling to an area with active cholera transmission; 

an intervention of lyophilized CVD 103-HgR single-dose, oral, live-attenuated bacterial vaccine; 

a comparison of no cholera vaccine; and the outcomes of moderate or severe cholera diarrhea, 

any severity of cholera diarrhea, SAEs, and/or non-SAEs. To summarize the EtR Framework 

presented on January 12, 2022, the WG felt that cholera is probably a public health problem 

among children and adolescents aged 2-17 years traveling to an area with active cholera of 

transmission. The WG determined that desirable anticipated effects were moderate, the 

undesirable anticipated effects were small, and that the balance of benefits and harms favors 

CVD 103-HgR with low overall certainty for the critical outcomes. The WG determined that CVD 

103-HgR is acceptable to key stakeholders, that the effect on equity varies, and that it is 

probably feasible to implement among children and adolescents aged 2-17 years traveling to an 

area with active cholera transmission. The WG determinations for values and resource use 

were “do not know.” The WG consensus was that desirable consequences probably outweigh 

undesirable consequences in most settings, given that there were only indirect data upon which 

to assess the desirable consequences. The WG consensus was to recommend the intervention 

CVD 103-HgR for children and adolescents aged 2-17 years traveling to an area with active 

cholera transmission.

In terms of considerations for prevention of cholera and use of CVD 103-HgR, CDC’s Travelers 

Health Branch updates the list of countries with active cholera transmission on a monthly basis.3

The destination pages specify whether cholera transmission is localized to certain areas or 

widespread.4 As of January 2022, the following 15 countries were considered to have active 

cholera transmission:

3 https://wwwnc.cdc.gov/travel/diseases/cholera 4 https://wwwnc.cdc.gov/travel/destinations/list 
ACIP Meeting Summary February 23-24, 2022 

14

 Africa: Benin, Cameroon, Democratic Republic of the Congo, Ethiopia, Kenya, 

Mozambique, Niger, Nigeria, Somalia, Uganda

 Asia: Afghanistan, Bangladesh, India, Nepal, Yemen

 Americas: None

 Pacific: None

Regardless of cholera vaccination status, travelers to cholera-affected areas should use 

personal protective measures. That is, they should consume safe food and water, wash hands 

often with soap and safe water, and follow recommended sanitation practices (e.g., using 

latrines or burying stool). More detailed prevention information is available on two CDC 

websites.5 shown on the slide.

CVD 103-HgR is the only cholera vaccine licensed for use in the US. It is a single-dose, live, 

attenuated, oral vaccine derived from Vibrio cholerae O1. Production has been temporarily 

discontinued during the COVID-19 pandemic, but the manufacturer has specified that it will be

available again beginning May 1, 2022. Regarding Dr. Brooks’ question in January about the 

number of doses administered, the manufacturer provided data indicating that 62,179 doses of 

CVD 103-HgR were sold in the US during 2016-2019. The WG did not have data on how many 

of those doses were administered. Although production began in 2016, ACIP approval for adults 

did not occur until June 2016. The initial authorization also required that the vaccine be stored 

frozen. Regarding administration setting, the WG feels the CVD 103-HgR may be optimally 

administered in a travel clinic, given the relatively complicated dose preparation and 

administration. However, as ACIP members noted previously, many travel clinics have closed 

during the pandemic and whether they will reopen is uncertain. The WG agreed that 

administration in non-travel clinics is permissible. Regardless of setting, CVD 103-HgR should 

be prepared and consumed in a medical office to minimize potential dosing errors. Providers 

should carefully follow instructions in the package insert.

The buffer component and active component packets should be stored refrigerated at 36oF to 

46oF (2oC to 8oC). Packets should not be out of refrigeration for more than 12 hours before 

reconstitution, and they should not be exposed to temperatures exceeding 80oF. They also 

should be protected from light and moisture. In accordance with the package insert,6 recipients 

should avoid consuming food or drinks for 60 minutes before and after vaccine administration 

and only cold or room temperature, purified bottled or spring water should be used to 

reconstitute the buffer. Tap water contains chlorine that can affect the viability of orally ingested 

live attenuated bacterial vaccines. Detailed preparation and reconstitution instructions are 

available in the package insert. First, the buffer is mixed with 100 milliliters of cold or room 

temperature purified bottled or spring water. According to Step 5 in the insert, the buffer solution 

should be mixed with a disposable stirrer until it completely dissolves. For children aged less 

than 6 years, half of the reconstituted buffer solution should be discarded after the buffer sachet 

is mixed with water. The active component packet is then added and stirred until it disperses to 

form a slightly cloudy suspension that may contain light particles. If the packets are 

reconstituted in the improper order, the vaccine must be discarded. The prepared vaccine must 

be consumed within 15 minutes.

5 https://www.cdc.gov/cholera/preventionsteps.html; https://wwwnc.cdc.gov/travel/diseases/cholera#areas 6 https://www.fda.gov/media/128415/download 
ACIP Meeting Summary February 23-24, 2022 

15

Administration of CVD 103-HgR with sweeteners is not currently covered in the package insert. 

As noted on January 12, 2022, the manufacturer anticipates a supplemental filing with FDA 

early in 2022. Unpublished data presented by the manufacturer in January 2020 demonstrates 

CVD 103-HgR is not compatible when mixed with medicine flavorings that contain propylene 

glycol or when mixed with food and drinks (e.g., rice cereal, applesauce, juice, or milk). Data 

presented support that the vaccine is compatible when mixed with 1-4 grams of sucrose or table 

sugar or 1 gram of stevia sweetener. Of the vaccine recipients 2-17 years of age, 93% in the 

clinical trial consumed the vaccine with PureVia Stevia. Providers also should advise recipients 

about the most common side effects within 7 days of CVD 103-HgR, including fatigue, 

headache, abdominal pain, nausea or vomiting, lack of appetite, and/or diarrhea. These adverse 

reactions were most commonly rated as mild in the clinical trials. No clinical trials have 

evaluated the safety or efficacy of booster doses of CVD 103-HgR in preventing cholera. The 

duration of protection beyond the 3-month period evaluated in adults 18-45 years of age is 

unknown. The serum vibriocidal antibody assay used in the pediatric clinical trials is likely a 

surrogate for protection mediated by intestinal mucosa.

In terms of co-administration with other medicines or vaccines, antibiotics might have activity 

against the vaccine strain. Therefore, CVD 103-HgR should be administered at least 14 days

after completion of either oral or intravenous (IV) antibiotics. A shorter duration may be 

acceptable if travel cannot be avoided but may diminish the effectiveness of the vaccine. The 

optimal duration between completion of CVD 103-HgR and starting antibiotics is unknown. In 

certain circumstances, antibiotics may be clinically necessary after the vaccine, such as to treat 

an unrelated infection. Nearly all (93%) of vaccine recipients in the clinical trials had 

seroconversion by 10 days, suggesting that administration of antibiotics after this may not affect 

protection. Chloroquine may diminish the immune response to CVD 103-HgR. Therefore, CVD 

103-HgR should be administered at least 10 days before starting chloroquine, such as for 

malaria prophylaxis. No data are available on concomitant administration with other vaccines. 

Enteric-coated, live-attenuated typhoid vaccine, Ty21a,7 is another common oral travel vaccine.

Experts suggest taking the first dose of Ty21a at least 8 hours after CVD 103-HgR. This might 

decrease potential interference of the buffer of CVD 103-HgR with the Ty21a vaccine.

Moving to contraindications and precautions, CVD 103-HgR is not licensed for children less 

than 2 years of age or adults ≥65 years. No data exist about the safety and effectiveness of the 

vaccine in these populations. CVD 103-HgR should not be administered to persons with a 

history of severe allergic reaction, such as anaphylaxis, to any component of this vaccine or to a 

prior dose of any cholera vaccine. No data are available regarding the current formulation of 

CVD 103-HgR during pregnancy or breastfeeding. Pregnant women are at increased risk for 

poor outcomes from cholera infection. Pregnant women and their clinicians should consider the 

risks associated with traveling to areas with active cholera transmission. The vaccine is not 

absorbed systemically. Therefore, maternal exposure to the vaccine is not expected to result in 

exposure to the fetus or breastfed infant. However, the vaccine strain might be shed in stool for 

at least 7 days after vaccination, and theoretically, the vaccine strain could be transmitted

to an infant during vaginal delivery.

No data are available regarding the current formulation of CVD 103-HgR in persons with altered 

immunocompetence. Persons with altered immunocompetence and their clinicians should 

consider the risks associated with traveling to areas with active cholera transmission. 

Consultation with a specialist in infectious diseases or immunology should be considered if 

travel to an area with active cholera transmission is necessary. ACIP generally advises against 

7

 Trade Name: Vivotif 
ACIP Meeting Summary February 23-24, 2022 

administering live vaccines to persons with most forms of altered immunocompetence.8

16

CVD 

103-HgR may be shed in the stool of recipients for at least 7 days. Patients should be 

counseled that the vaccine strain can potentially be transmitted to non-vaccinated close 

contacts such as household contacts, and to wash their hands thoroughly after using the 

bathroom and before preparing or handling food for at least 14 days after vaccination.

Given all of these considerations, the WG proposed the following draft recommendation for 

ACIP consideration:

Lyophilized CVD 103-HgR is recommended for children and adolescents aged 2-17 

years traveling from the United States to an area with active cholera transmission. 

Discussion Summary

Dr Poehling noted that for many oral vaccines, consideration is given to withholding the vaccine 

if there are persons with serious immunocompromising conditions in the family. With that in 

mind, she asked whether this would be a consideration for the cholera vaccine. 

Dr. Collins indicated that the package insert notes that providers should consider whether to 

administer the vaccine if the recipient has an immunocompromised household or other close 

contact. The WG discussed this and felt that that language was somewhat strong. In a small 

study of the preliminary formulation of CVD 103-HgR, there was no household transmission.

This study included 66 healthy adults who were randomized 5:1 to vaccine or placebo. Stool 

shedding occurred in 11% of vaccine recipients. The study also enrolled 24 household contacts 

of vaccine recipients. None had the vaccine strain isolated from stool on a Day 7 specimen, and 

none had virucidal seroconversion on a Day 28 specimen. This may depend on the individual 

and providers may want to counsel people who they do not think have access to adequate 

hygiene and sanitation measures. Most people in the US do have adequate access. With 

adequate hand washing and sanitation, the WG did not feel like the risk posed to household 

contacts acquiring it was substantial enough to recommend withholding vaccine. The WG also 

noted that the vaccine has been attenuated.

While mention was made that the duration of protection is unknown, Dr. Loehr pointed out that 

the background information provided to ACIP members in preparation for this meeting included 

a study of long-term immunogenicity that was published in 2021 that showed that 65% of people 

have seroprotection at 2 years. He asked Dr. Collins to comment on that, whether they should 

trust the seroprotection data, and if she was just saying that there are no randomized controlled

trial (RCT) data with actual disease. 

Dr. Collins indicated that essentially, there are no long-term efficacy data in which an oral

challenge study has been conducted. That would be the gold standard to determine whether the 

vaccine is still effective that far out. The data to which Dr. Loehr referred were data the

manufacturer shared during the February 2021 presentation. Based on those data,

seroconversion rates and geometric mean titer (GMT) levels remain somewhat high up to 2 

years out. The issue is that it is unknown how good of a marker of long-term protection serum 

vibriocidal antibody antibodies are. Her understanding is they may not be the best marker of 

long-term protection. This is the best available and best accepted measure to use in clinical 

trials in which efficacy is not being directly assessed. While serum vibriocidal antibody 

8 https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html 
ACIP Meeting Summary February 23-24, 2022 

17

antibodies are the best immunologic parameter available, they are mostly a surrogate and are 

not likely mechanistic. Instead, they are a marker of complement-mediated bactericidal activity

that does not really account for why they would explain the protection that is thought to be

mediated by an immune response at the intestinal mucosa. While these data are encouraging in 

some ways, the experts in the field would not necessarily trust them to say that the vaccine is 

protective that far out without an oral challenge study.

Dr. Long observed that the statement to “wash hands thoroughly after using the bathroom and 

before preparing or handling food for at least 14 days after vaccination” suggested that hand 

washing was not recommended any other time after these activities. She suggested stating that 

hand washing is always recommended after using the toilet and adding after diaper changes 

since some 2-year-olds are still in diapers. It should state that hand washing always should be 

done in these cases, but should be done with special attentiveness during the period of 

shedding vaccine bacteria.

Regarding pregnancy and the potential for exposure of the infant during vaginal delivery, Dr. 

Kimberlin (AAP Redbook) asked whether there was any consideration by the WG of interfacing 

with the American College of Obstetricians and Gynecologists (ACOG) to determine whether a 

limitation should be made during which the vaccine should not be administered to pregnancy 

women, such as after 36 or 38 weeks to minimize vaginal transmission.

Dr. Collins indicated that the WG did not directly discuss that. The WG was focused primarily on 

children and adolescents 2-17 years of age. Of course, adolescents can become pregnant. This 

language came from the previous adult Morbidity and Mortality Weekly Report (MMWR), but 

ACOG’s input would be welcomed.

Dr. Ault recalled that this was discussed previously when the focus was on adults. The best 

advice would be not to go to the area with cholera. This issue arose when CDC workers were 

going to Haiti a few years ago. He did not have any problems with the way the recommendation

was worded and pointed out that experience with these vaccines would be gained as they get 

used more often, including during pregnancy. 

Dr. Sanchez indicated that the WG did not specifically comment about not giving the vaccine in 

the 14 days before planned delivery. It would be important to ascertain the risks versus benefits. 

It may be better for a woman who may be exposed during that time to receive the vaccine. 

Consideration also should be given to the fact that it is an attenuated strain. 

Dr. Collins pointed out that the ACOG statement discusses travel in general during pregnancy.

Their statement says most commercial airlines allow pregnant women to fly up to 36 weeks of 

gestation, some restrict pregnant women from international travel or from international flights 

earlier in gestation, and some require documentation of gestational age.

Dr. Long said she was expecting to see the vaccine recommended for children with no 

contraindicating underlying immune deficiencies versus recommending it for all children.

Dr. Collins indicated that the WG discussed that there is a lack of data in immunocompromised 

children and adolescents upon which to make a decision. The WG members shared Dr. Long’s 

concern about providing the vaccine to children who are immunocompromised, particularly with 

severe immunocompromising conditions. Some of the rationale behind the proposed language 

was for clarity to harmonize it with the language for adults. The recommendation for adults 18-

64 years of age is straightforward, with the stipulation about persons with immunocompromising 
ACIP Meeting Summary February 23-24, 2022 

18

conditions included in the guidance. She stressed that the WG certainly would welcome further 

discussion about whether that is the correct approach.

Dr. Sanchez indicated that the WG did discuss this and were of the opinion that it 

immunocompromising conditions should be taken up in clinical considerations in terms of 

potential precautions against the use of the vaccine in such children and adolescents.

Dr. Wharton added that for many vaccines, contraindications and precautions are not 

necessarily included in the recommendation statement. Those are typically included as 

additional clinical information that accompanies the recommendation statement.

Dr. Poehling made a minor editorial suggestion to remove “from the United States” because it 

did not add anything and some people may be traveling through the US on a circuitous route to 

an active cholera transmission area, with which other ACIP members agreed.

Vote: Cholera Vaccine Recommendation 

Dr. Jennifer Collins (CDC/NCEZID) presented the proposed recommendation, including the 

revised language based on the editorial suggestion to remove “from the United States,” as 

follows:

Lyophilized CVD 103-HgR is recommended for children and adolescents aged 2-17 

years traveling to an area with active cholera transmission. 

Motion/Vote: Cholera Vaccine

Dr. Poehling made a motion for ACIP to adopt the recommendation stating that, “Lyophilized 

CVD 103-HgR is recommended for children and adolescents aged 2-17 years traveling to an 

area with active cholera transmission.” Dr. Daley seconded the motion. Dr. Chen declared that 

his employing institution, University of Maryland, received a grant from Emergent BioSolutions 

that supported the work he conducted to develop a Shigella vaccine, which constitutes a conflict

and resulted in his abstention from this vote. The motion carried with 14 affirmative votes, 0 

negative votes, and 1 abstention. The disposition of the vote was as follows:

14 Favored: Ault, Bahta, Bell, Brooks, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, 

Poehling, Sanchez, Talbot

 0 Opposed: N/A

 1 Abstained: Chen 

 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:

Dr. Chen emphasized that while having a cholera vaccine is terrific, there are many other 

diarrheal disease agents throughout the world that afflict and create major inequities in 

vulnerable populations such as very young children; low- and middle-income countries; and 

countries that do not have intact clean water, sanitation, and hygiene. His career focuses on 
ACIP Meeting Summary February 23-24, 2022 

19

trying to develop other diarrheal vaccines and he aspires to seeing that these types of vaccines

are available in the countries in which these diseases are endemic.

INFLUENZA VACCINE

Session Introduction

Dr. Keipp Talbott (ACIP, WG Chair) introduced this session, indicating the presentations 

would include a review of vaccines for older adults in terms of literature retrieved, meta-analysis 

results, GRADE, and the discussion of a modeling assessment that was done to determine the 

potential impacts of preferential recommendations for influenza vaccines in this population.

Influenza vaccines have been recommended for adults over 65 years of age and those at high 

risk for many years now. That recommendation preceded the ACIP and was issued by the 

Surgeon General. Influenza is unique in that while there is a new vaccine every year with 4 virus 

strains, it tends to be thought of as one vaccine. This variation coincides with the variation in the 

vaccine strains and the circulating virus strains. The data reviewed for older adults has included 

RCTs, which are typically considered to be the gold standard. Unfortunately, 1 or 2 years of 

data in an influenza year is equal to 1 or 2 years of data in influenza. It is extremely important

for the WG and WG leads to review all of the observational data associated with enhanced 

vaccines and older adults. These data are incredibly relevant because they will span seasons

and provide more information about head-to-head vaccines. She emphasized that the data to be 

presented represented an incredible amount of work for which the WG could not thank their 

CDC colleagues enough. As they reviewed all of these data in a very condensed and dense 

format, she expressed her hope that the rest of the ACIP voting members would ask questions.

Influenza Activity Update

Dr. Lisa Grohskopf (CDC/NCIRD) provided a brief update on domestic influenza activity. The 

percent of assessments that were positive peaked in December 2021 at about 6% and 

subsequently declined to about 2% by mid-January 2022. However, 3% of specimens submitted 

to the clinical laboratories were positive for the most recent reporting week of February 12, 2022 

(Week 6). Most positive specimens were influenza A, with most subtyped specimens being 

H3N2. These viruses thus far have been genetically closely related to the vaccine virus, but 

there are some antigenic differences that have developed as H3 viruses have continued to 

evolve. Influenza like illness (ILI) activity peaked in mid- to late-December and declined to below 

the epidemic threshold since then. Sporadic influenza activity continues throughout the country 

and is increasing in some parts of the country. This season, cumulative hospitalizations are 

tracking higher than the 2021 season, but are still substantially lower than the previous four 

seasons 2016-2017 through 2019-2020. The cumulative hospitalization rate thus far this season 

is 4.7/100,000. For the current week, 22.6% of deaths were attributed to pneumonia, influenza, 

or COVID-19. Only 1 pediatric death was reported for the 2020-2021 season, while a total of 5 

pediatrics deaths have been reported thus far for the 2021-2022 season.

In terms of preliminary interim VE for influenza vaccines, the US Flu VE Network is comprised of 

7 sites and provides estimates of laboratory-confirmed medically-attended influenza

illness each season. The US Flu VE Network enrolled outpatients ≥6 months of age with acute 

respiratory illness (ARI) and cough of less than or equal to 7 days duration. Through January 

22nd, 2,758 persons have been enrolled at the 7 sites. Of these, 147 (5%) were positive for 

influenza, which is fairly low. For the influenza A viruses isolated, all subtyped viruses have 

been H3N2 and all sequenced viruses of H3N2 belong to a single genetic group 3C.2a1b, 
ACIP Meeting Summary February 23-24, 2022 

20

Subclade 2a.2. To summarize early preliminary interim VE against influenza A and H3N2 

among patients ≥6 months of age thus far this season, for influenza A for all ages, adjusted VE 

was 8% with a 95% confidence interval of -31% to 36%. VE for H3N2 was 14% with a 95% 

confidence interval of -28% to 43%.

To note some limitations that are important to consider when thinking through these data, this is 

the lowest influenza positivity rate (5%) observed over the past 10 seasons among US Flu VE 

network participants with respiratory illness. Numbers of influenza-positive participants were 

insufficient to estimate age groups specific VE or to compare effectiveness of different influenza 

vaccine products against the predominant A(H3N2) virus. Moreover, healthcare seeking 

behavior has changed during the COVID-19 pandemic in ways that might affect influenza VE. 

VE estimates are limited to mild illness and evaluation of VE against influenza hospitalizations is

ongoing this season. Again, it is important to note that these are preliminary interim data that 

are expected to change over time.

Discussion Summary

Dr. Brooks requested clarity about which VE estimate mentioned for A(H3N2), 33% versus 14%, 

was more indicative of the true VE. 

Dr. Grohskopf clarified that because these are observational data and adjustment for 

confounders would be important, it would be the adjusted estimate of 14% for all A(H3N2). 

Dr. Long emphasized that it was becoming trickier to talk about percent positive specimens. The 

problem is when dealing with percent positives in the middle of a pandemic, and especially with 

the Omicron surge, numbers for influenza in the middle of December would have been about 

this 6%. But if the aberration of the pandemic and all of the specimens that were COVID-19 

specimens, it seems that about 25% to 30% would have been influenza positive. It seemed 

misleading to her, especially for the public, to be talking about percent when the denominator 

was unknown and it is unclear what percent were related to a surge of COVID-19. She 

expressed her hope that they could find a better way to describe the activity of a virus rather 

than percent of positive specimens.

Dr. Fry responded that CDC focused on symptomatic people, not asymptomatic people. That is 

where a lot of the confusion with Coronavirus occurs. In this particular case in the CDC 

surveillance systems, these estimates were among people who presented for testing with an 

ARI who tested positive for influenza. There also is a percent who tested positive for COVID-19, 

which is the differential diagnosis. COVID-19 makes things very complicated in terms of who is 

being tested, local circulation, et cetera. This makes it difficult sometimes to tease everything 

out completely.

Recommending Enhanced Seasonal Influenza Vaccines in Adults ≥65 Years of Age: 

Potential Impacts on Influenza Burden

Dr. Sinead Morris (CDC/NCIRD) reported that the primary goal for this effort was to use 

mathematical modeling to explore how a new preferential recommendation for enhanced 

vaccines (e.g., high-dose, adjuvanted, recombinant) over standard vaccines (SVs) in adults ≥65 

years of age could impact influenza burden over the course of the season. The approach to the 

model included 2 elements, which were to: 1) create a baseline model to capture influenza 

dynamics under current guidelines when there is no preferential recommendation in place; and 
ACIP Meeting Summary February 23-24, 2022 

21

2) model what might happen following a preferential recommendation for enhanced vaccines 

(EVs). 

The baseline model was created in order to have something with which to compare everything 

else. Because influenza burden can differ from season-to-season, consideration was given to a 

high severity season and a low severity season. While this does not represent any particular 

season, it can be thought of as the high severity season representing a season dominated by 

H3N2 and the low severity season being more similar to a season dominated by H1N1. The 

model used was an age-structured Susceptible Exposed Infectious Removed (SEIR) model in 

which individuals were stratified based on age and disease status. People start out susceptible 

and then upon infection, they progress through a series of states where they are first exposed 

but not yet infectious. Then they become infectious and potentially symptomatic. Finally, they 

recover and are assumed to be immune for the remainder of the season. Vaccination also was 

incorporated into the model, with adults under 65 years of age receiving SV and adults ≥65 

years of age receiving either SV or EV that offers greater protection. The model is first 

calibrated by using published parameter estimates from the literature and verifying that it can 

capture the dynamics that would be expected in typical high and low severity seasons.

One example is the efficacy produced by the model for the number of symptomatic cases per 

100,000 people. The model was recalibrated so that the high severity season had a higher and 

an earlier peak than the low severity season, as is often the case for H3 versus H1 dominated 

seasons. The peak for seasons over the last 10 years was used to verify that the timing of the 

peak produced by the model agreed with what was seen in product data quality (PDQ). Other 

calibration checks were performed as well. Once the modelers were satisfied that the model 

was producing reasonable dynamics, they moved on to the second step.

The second step of the model explores what might happen following a preferential 

recommendation for EVs. First, it was assumed that there would be benefits to new 

recommendations. For example, if given the choice, more people would choose an EV over an 

SV standard vaccine, meaning that the percentage of adults ≥65 years of age getting an EV 

would increase. But the model also explored the potential tradeoffs that could occur. For 

example, there could be a delay in people receiving those additional EVs if there was higher 

demand or it took longer to find a provider who offers that vaccine. There also could also be a 

reduction in overall coverage in the ≥65 years of age group if individuals only offered SVs did 

not take them. Monetary or individual costs like safety were not considered in the model. 

Instead, the model focused on the opportunity costs from a society perspective.

To model the impact of a new recommendation, values had to be assigned to the benefits and 

opportunity costs. For the benefits, the percentage of vaccinated adults ≥65 years of age to 

receive an EV can increase by up to 20% compared with the baseline value with no 

recommendation. For example, if the percentage receiving an EV at baseline is 75% and an 

increase of 10% is assumed, 85% would receive an EV with the new recommendation. For 

opportunity costs, 3 levels of possible delays and reduction in overall coverage were 

considered. The best case was when delays and reduction in overall coverage were 0, or all the 

benefits without any additional cost. For the intermediate values, a 3-week delay and a 10% 

reduction in overall coverage were used. For the worst-case options, a 6-week delay and a 20% 

reduction in coverage were used. It is important to note that no assumptions were made about 

how likely any of these different opportunity costs were to occur. They were just used to explore 

a range of possible outcomes.
ACIP Meeting Summary February 23-24, 2022 

22

In addition, 2 other important parameters were varied in this analysis. First, it was assumed that 

EVs were between 5% and 50% more effective than SVs, which translates to an effectiveness 

of 26% to 60% in absolute terms. This wide range reflects the large variation and uncertainty in 

estimates from the literature, one of which was a 2014 paper used to calibrate this frame.9

Second, it was assumed that at baseline with no recommendation in place, between 60% and 

80% of vaccinees ≥65 years of age received EV and the remaining fraction received SV. This 

range was based on a number of recent studies with some additional uncertainty included.10 To 

incorporate all of these components into the model, the benefits and those 2 important EV 

parameters were varied between the ranges outlined earlier (parameters varied 1000 times, 

benefits increased EV uptake by 0%-20%, EV effectiveness of 5%-50% greater than SV, and 

EV uptake at baseline of 60%-80% of vaccinees 65+). Uncertainty was directly incorporated in 

these values in the analysis. For each combination of the opportunity cost parameters, the 

model was simulated with and without a preferential recommendation in place. The change in 

hospitalizations and deaths that occurred also were calculated.

In terms of the number of hospitalizations that were averted with a new recommendation in 

place, the delay in receiving additional EV was increased from 0 to 3 to 6 weeks. The reduction 

in overall coverage was increased across the columns from 0 to 10% to 20%. The first important 

takeaway is that, as might be expected, when both parameters were at their best-case values of 

0, a positive change was always seen or was better with the recommendation in place. That 

makes sense because this assumes all of the benefits without any of the opportunity costs. 

Increasing the delay while keeping a 0% reduction in overall coverage introduced some 

potential for negative impacts in the high severity season, while the impact remained mainly 

positive in the low severity season, so the benefits could still outweigh the opportunity costs. 

However, if instead the reduction in overall coverage was increased to 10, there was always a 

negative impact that increased as the reduction increased to 20%. For the parameter values 

explored here, the opportunity costs also could outweigh the benefits quite substantially. 

Importantly, the magnitude of this effect was more sensitive to the reduction in overall vaccine 

coverage.

To note some of the limitations to the approach and important points to keep in mind when 

interpreting these results, first, it was assumed that vaccines only protect against symptoms

(i.e., no additional effect on infection or onward transmission). Thus, the results focus on the 

direct effects of vaccination without consideration for how indirect effects may change these 

results. Second, high and low severity seasons were used to explore a range of possible 

outcomes that could be expected. They do not represent any one particular season and are not 

exact predictions. Third, EVs were not stratified by type (high-dose, adjuvanted, recombinant). 

However, a wide range of parameter values were explored that should account for variations in 

uptake and effectiveness between the different vaccine types. Fourth, the tradeoff scenarios 

made necessary assumptions about how individual vaccine-seeking behavior might change. 

These were used to provide examples of the range of possible outcomes, but the model did not 

assess how likely they are to occur.

To summarize the main findings, in the best-case scenario with no delays or reductions

in overall coverage, a new recommendation always has a positive impact. However, switching 

to the intermediate- or worst-case values can introduce negative impacts that can range from 

relatively small to more substantial. Overall, the outcomes are more sensitive to the reduction in 

overall vaccine coverage. In terms of what could be done to maximize the chance of having a 

9

 Diaz Granados et al. (2014) NEJM 

10 Izurieta et al. (2019, 2020, 2020) JID, CID
ACIP Meeting Summary February 23-24, 2022 

23

positive impact, the results so that it is necessary to get as close to the best-case scenario as 

possible and to avoid delays in vaccine uptake. For instance, this can be achieved by ensuring 

timely access to EVs and minimizing reductions in overall coverage by stressing the importance 

of still getting SV if EV is not available.

Discussion Summary

Based on current distribution numbers, Dr. Lee inquired about the likelihood of an adult ≥65 

years of age going to a vaccination site that did not have an EV available, whether there is 

regional or local variability in availability that could impact some communities more adversely

than others, and if there has been an assessment of potential gaps that need to be closed from 

an implementation standpoint.

Dr. Talbot indicated that approximately 80% of adults currently get an EV. One of the reasons 

the WG greatly appreciated this presentation was that if ACIP recommends only 1 vaccine as 

EV and only 1 vaccine as preferential and there was a delay in that vaccine, there may be an 

issue in the timing of immunization of older adults. If more than 1 vaccine is recommended, this 

would provide more options and reduce the likelihood of a manufacturing or contamination 

issue, which would then lead to a delay in immunization in older adults.

Dr. Drees (SHEA) asked when a decision about a preferential recommendation would be made. 

While ACIP was not going to vote on this during this meeting, everyone is ordering their 

influenza vaccines now for the next season. If a vote is planned for June or October, that would 

be problematic in terms of most places not having ordered a sufficient supply for an increase in 

demand and would impact uptake as well.

Dr. Talbot noted that this is always an issue with influenza vaccine, given that there is a new 

vaccine every year. One issue is that the full data analyses and information from GRADE took 

slightly longer than anticipated because of the 2-year pandemic in which everyone has been 

participating and continues to participate. The GRADE assessment was finally completed and 

the WG reviewed it and was excited to share it with the rest of the ACIP voting members later in 

this session. The next step would be the EtR framework, after which a vote could be taken, 

which may conflict with influenza purchasing times.

Dr. Daley asked whether vaccine supply posed any major issues, what is known about the 20% 

of older adults who received SV, whether that was because EV was not available, and/or if 

logistics played a role.

Dr. Talbot responded that there are not currently any supply issues. There have been issues in 

the past, the most memorable of which occurred in 2005. Among the 20% of older adults who 

do get vaccinated each year but not with EV, it is likely due to the location to which they have 

presented no having EV. Although currently there is not a preferential recommendation, many 

but not all hospitals and healthcare systems purchase EV for adults over 65 years of age. The 

question of who over 65 years of age is not getting vaccinated is one that needs further 

exploration and improvement.

In terms of the best-case scenarios that were highlighted, Dr. Bell wondered whether there is a 

way to look at the Y axis to explain in more detail exactly how much incremental benefit the 

preferential recommendation might provide.
ACIP Meeting Summary February 23-24, 2022 

24

Dr. Morris replied that this would be possible. While she did not have the exact numbers, the 

mean is about 1,000 and the bar probably goes up to about 3,000. It is important to remember 

that the seasons are modeled on what would be expected in a typical influenza and are not fit to 

any one season in particular. Therefore, these are not exact predictions of what would happen.

Influenza Vaccines for Older Adults 

Dr. Lisa Grohskopf (CDC/NCIRD) reminded everyone that as described in previous meetings, 

older adults are defined as adults ≥65 years of age. This group is at high risk for influenzaassociated morbidity and mortality, but also is a group for whom influenza vaccines are often 

less effective than is the case for younger persons. Influenza vaccines licensed for this 

population include high-dose influenza vaccine (HD-IV), adjuvanted influenza vaccine (aIIV), 

and recombinant influenza vaccine (RIV) licensed for adults ≥18 years of age and have been 

studied against standard dose IIV (SD-IIV), unadjuvanted, and inactivated influenza vaccines in 

this population. For this presentation, these 3 vaccines were referred to collectively as EIVs. 

This review sought to answer the following question. “Do the relative benefits and harms of HDIIV, aIIV, and RIV (referred to collectively as enhanced influenza vaccines or EIVs) as compared 

with one another and with standard-dose unadjuvanted influenza vaccines (SD-IIV) favor the 

use of any one or more of these vaccines over other age-appropriate influenza vaccines for 

persons ≥65 years of age?”

In terms of the PICO, the population of interest is adults ≥65 years of age. Interventions of 

interest included EIVs (HD-IIV, aIIV, and RIV)—quadrivalent and trivalent formulations. EIVs 

were compared with SD-IIVs, as well as with one another. Critical benefits include influenza 

illness, influenza-associated outpatient/ED visits, influenza-associated hospitalizations, and 

influenza-associated deaths. Important harms outcomes included occurrence of any SAE and 

any solicited injection site reactions Grade 3 or higher. Critical harms included occurrence of 

any solicited adverse reaction Grade 3 or higher and Guillain-Barré Syndrome (GBS). There 

were 6 total of vaccine comparisons as shown in this table:

EIVs vs SD-IIVs EIVs vs One Another

HD-IIV vs SD-IIV HD-IIV vs aIIV

aIIV vs SD-IIV HD-IIV vs RIV

RIV vs SD-IIV aIIV vs RIV 

The analyses considered influenza seasons separately where possible because the VE of these 

vaccines and relative VE of vaccines to one another vary from season-to-season. Comparisons 

of trivalent and quadrivalent vaccines are combined, given data indicating that quadrivalent 

formulations have been roughly equivalent in terms of safety and immunogenicity to their 

trivalent counterparts. In cases where a study recorded separate estimates for different IIV 

comparator vaccines, the SD-IV was generally selected and was specified as egg- or cellbased. The egg-based comparator was included since that is probably the most likely scenario 

given the currently availability of vaccines. Estimates for composite outcomes (e.g., combined 

inpatient/outpatient visits; hospitalizations/ER visits) were not included in the main analyses or 

GRADE and were described separately.

For Comparison 1 (HD-IIV vs SD-IIV), there was a high certainty of evidence (Level 1) for the 

outcome of influenza illnesses favoring HD-IIV3 over SD-IIV. This is based on a single large 

RCT that included roughly 32,000 persons ≥65 years of age covering 2 influenza seasons and 

that used a laboratory-confirmed influenza outcome. There was moderate quality evidence 

favoring HD-IIV for influenza-associated outpatient and ER visits from retrospective cohort 
ACIP Meeting Summary February 23-24, 2022 

25

studies. This result was downgraded because of risk of bias given the cohort design of the study 

and use of the non-laboratory confirmed influenza outcomes. For hospitalizations, there was not 

an RCT that directly evaluated influenza-specific hospitalizations as a primary outcome. 

However, 2 RCTs examined hospitalizations and other severe events as a secondary post-hoc 

analysis, and 1 case review of diagnostic codes associated with SAEs that occurred in a 

previous trial and in the other 2 chart reviews. Neither of these outcome definitions involved 

influenza testing performed within the context of the study. There was no significant difference 

with moderate certainty evidence (Level 2). However, for hospitalization, there also was 

moderate certainty evidence (Level 2) favoring HD-IIV3 against pneumonia and influenza-coded 

hospitalizations from a cluster randomized trial, as well as from a number of observational 

studies primarily of a retrospective cohort design. These were downgraded to moderate 

certainty (Level 2) on the basis of using diagnostic code-defined outcomes rather than 

laboratory-confirmed outcomes. Finally, there was moderate certainty (Level 2) evidence 

favoring HD-IIV3 against influenza-associated death, which was downgraded primarily because 

of potential risk of bias from using a code-based definition for the outcomes.

Moving on to harms, there was high certainty (Level 1) evidence favoring HD-IIVs for SAEs. In 

the 2 pathogenicity outcomes, the point estimate for solicited injection site reactions Grade 3 or 

greater was approximately 4.9 (0.85, 28.36). However, it did not meet statistical significance due 

to a wide confidence interval. There was overall low-quality (Level 3) evidence for a similar risk

of Grade 3 or higher local or systemic reactogenicity events and it was downgraded due to 

imprecision. It is not easy to study GBS in an RCT. However, 1 RCT reported on GBS as an 

adverse event of special interest (AESI) as specified in the protocol. No cases were recorded in 

either group in that paper.

For Comparison 2 (aIIV vs SD-IIV), there were no RCTs examining laboratory-confirmed 

influenza outcomes. The 1 RCT was primarily an immunogenicity and safety study that 

examined clinical effectiveness against ILI using a symptomatic definition as an exploratory 

outcome with no laboratory confirmation. It was not powered to attest to efficacy. No compatible 

studies of other types were found that could be pooled with these data. The study noted no 

significant difference in ILI, and it was downgraded due to risk of bias concerns given the nonlaboratory-confirmed outcomes. However, there was some mixed evidence with regard to 

influenza-associated outpatient visits from a mix of study types. These results could not be 

pooled into one result because of differences in the statistical analyses and denominator 

techniques, so there were 2 separate estimates—one showing a significant difference favoring 

adjuvanted vaccines and the other showing no significant difference. Overall quality for this 

group of studies was moderate (Level 2) and was downgraded because most of the data came 

from studies using code-based rather than laboratory-confirmed outcomes. There was 

somewhat stronger and more uniform evidence for influenza-associated hospitalizations. This 

was somewhat more consistent across study designs, similar to what was see in the last 

comparison of HD-IIV3 versus SD-IIV. The pooled estimates favored IIV versus SD-IIV, with 

moderate certainty (Level 2).

With regard to harm, there was no significant difference for safety outcomes in the pooled 

estimate for any SAE with moderate certainty (Level 2) due to imprecision. There was low 

certainty evidence (Level 3) favoring SD-IIV for injection site reactogenicity events. This was 

downgraded for imprecision of the confidence interval. This result was driven largely from 1 

study which noted that there were no severe pain events in either vaccine group. There was no 

significant difference in systemic reactogenicity events, with downgrading for uncertainty due to 

imprecision. One of the general themes here is that for many of the safety outcomes, the main 

source of downgrading is the precision of the confidence interval. For the last outcome of GBS, 
ACIP Meeting Summary February 23-24, 2022 

26

there was 1 RCT of adjuvanted versus standard dose that noted 1 instance of GBS in the SDIIV3 group. There also was 1 retrospective cohort study of 3 seasons from Italy that noted zero 

cases of Definite, Probable, or Possible GBS in either arm during a 42-day window.

Regarding Comparison 3 (RIV vs SD-IIV), 2 RCTs were retrieved that addressed influenza 

illnesses with a pooled estimate showing no significant differences and moderate certainty 

(Level 2) due to imprecision. For influenza-associated hospitalizations, there was 1 

retrospective cohort study of CMS data. This estimate favored RIV with moderate certainty 

(Level 2). In terms of harms, with any SAE and both reactogenicity outcomes, the pooled 

estimates also were RCTs that indicated no significant differences. For all cases, outcomes 

were low (Level 3) largely due to imprecision. For GBS, there was one retrospective cohort 

study of trivalent recombinant versus inactivated standard dose vaccine that had this as an 

outcome. There were 4 cases that all occurred among SD-IIV3 recipients and none among RIV 

recipients that occurred within a 41-day post-vaccination window. Certainty was very low (Level 

4) because of the diagnostic code-based outcomes and imprecision.

Turning to Comparison 4 (HD-IIV3 vs aIIV3), there was one small RCT for the illness outcome

(used for all 3 EIV versus aIIV3 outcomes). This RCT included a total of about 90 people and all 

3 intervention vaccines (HD-IIV3, aIIV3, and RIV4). It was primarily an immunogenicity and 

safety study that included polymerase chain reaction (PCR)-confirmed ILI only as an exploratory 

outcome. This study was not powered for efficacy. No additional data were found with which to 

pool these data. It was included here for completeness. For the first outcome, there was no 

significant difference between the HD-IIV and aIIV groups. They were downgraded for risk of 

bias as this is an open label study and has imprecision. For influenza-associated outpatient ER 

visits, there were 3 retrospective cohort studies with no significant difference in the pooled 

estimates. Certainty was downgraded due to the use of non-laboratory confirmed outcomes and 

inconsistency of the estimates that were observed in this study. For influenza hospitalizations, 

there were 4 retrospective cohort studies. There was no significant difference between group 

estimates. Certainty was downgraded due to the use again of non-laboratory confirmed 

outcomes and imprecision. In terms of harms, there was low certainty (Level 3) evidence of a 

similar risk of SAE Grade 3 or higher for injection site or systemic reactogenicity events, which 

were roughly equivalent between the 2 groups. For GBS, there was 1 RCT that included GBS 

as an AESI for this comparison. No cases were reported in the paper for either group.

For Comparison 5 (HD-IIV3 vs RIV4), the data became sparser because there is not as much 

literature on RIV as on the other vaccines. For influenza illnesses, there was the same small 

RCT mentioned in the last comparison that examined PCR-confirmed ILI and exploratory 

outcomes, with no significant difference in ILI between groups. This was downgraded again 

because of the imprecision due to the small sample size and being an open label study. For 

hospitalizations, there was one retrospective cohort study, which was a fairly large CMS study. 

However, it was for one season and had an effect estimate favoring RIV4. Certainty was 

downgraded because of the use of diagnosis code-based outcome data rather than laboratoryconfirmed data and for imprecision in the study. For safety outcomes for this comparison, there 

were 2 RCTs that each addressed the any SAE and both reactogenicity outcomes. There were 

no significant differences between the vaccine groups for any outcomes. Certainty was 

downgraded for imprecision.
ACIP Meeting Summary February 23-24, 2022 

27

With regard to Comparison 6 (aIIV3 vs RIV4), there was the same small RCT mentioned earlier. 

There were no significant differences between the 2 conditions. This was downgraded for 

imprecision and having been an open label study. For hospitalizations, there was 1 

retrospective cohort study with an effect estimate favoring RIV4. Certainty was downgraded to 

moderate (Level 2) because of the use of diagnostic code-based outcome definitions rather

than laboratory confirmation. With regard to harms and safety outcomes for this comparison, 

there was 1 RCT that addressed each of the SAEs in both reactogenicity outcomes. This study 

observed no significant differences between the 2 vaccines groups for any outcomes and 

certainty was downgraded for imprecision. The following 2 tables assemble all of the evidence 

across outcomes:

For HD-IIV3 and SD-IIV, there was high certainty evidence favoring HD-IIV3 for influenza 

illnesses and moderate certainty evidence for outpatient visits, hospitalizations, and deaths.

For safety outcomes, there was high certainty evidence favoring HD-IIV3 for SAEs, with the 

remaining safety outcomes favoring neither vaccine and having low certainty, mainly due to 

imprecision of estimates. For adjuvanted influenza vaccines, there was moderate certainty 

evidence favoring neither vaccine for illnesses and outpatient visits, but there was moderate 

certainty evidence favoring aIIV for hospitalizations. For safety outcomes, there was moderate 

certainty evidence of similar risk of SAEs and low certainty evidence favoring SD-IIV for local 

reactogenicity. For RIV, there was moderate certainty evidence favoring neither vaccine for 

illnesses and moderate certainty evidence favoring RIV4 for hospitalizations. For SAEs and 
ACIP Meeting Summary February 23-24, 2022 

28

reactogenicity outcomes, there was low certainty evidence of similar risks of these events. 

Overall, there was relatively little data on GBS, with low to very low-quality evidence

across the 3 comparisons.

For comparisons of EIVs versus one another, there were no significant differences except 

moderate certainty evidence favoring RIV4 over both HD-IIV3 and aIIV3 for hospitalization

among the 4 efficacy outcomes. This was on the basis of 1 observational study conducted over 

1 season. This was a study of a retrospective cohort of CMS data totaling roughly 13 million 

people. For safety outcomes, the evidence review was overall low mainly due to imprecision of 

estimates, and there were no significant differences for any outcomes.

In conclusion for EIVs vs SD-IIVs, there was limited RCT data. There were mainly 2 studies that 

examined laboratory-confirmed influence outcomes, 1 for high-dose and 1 for recombinant. 

These represent relatively few influenza seasons overall. With influenza, examining seasons is 

important because of the variability of both VE and relative VE. There was high quality evidence 

favoring HD-IIV3 over SD-IIV3 from 1 RCT specifically for the illness outcome. Evidence for the 

other outcomes fell more into moderate certainty evidence. From observational data, there was 

overall moderate certainty evidence favoring each EIV over SD-IIV against influenza-related 

hospitalization, which is an important outcome in this population. The limitations of these data 

include that they were mostly from large retrospective cohort studies for which outcomes were 

defined by diagnostic codes rather than laboratory-confirmed influenza. However, they did have 

a very large sample size and in some cases were conducted over multiple seasons. Moreover, 

many of them used relatively specific influenza codes rather than pneumonia and influenza 

codes. Although there were some of the latter as well. The largest quantity of data were 

available overall for HD-IIV3, somewhat less for aIIV3, and the least with regard to RIV. Overall, 

there were a few differences in safety outcomes and none for critical outcomes.

With regard to EIVs versus one another, there were more limited data. In general, there was 

only very low certainty RCT data from 1 study that was not intended to examine efficacy as a 

primary outcome. From observational data, there was moderate quality evidence favoring RIV 

over both HD-IIV3 and aIIV3 against hospitalization. However, this was from 1 retrospective 

cohort study conducted over a single season. No safety differences were observed among the

three EIV comparisons, and overall evidence providing direct comparisons of EIVs with one 

another did not seem to indicate superiority of any 1 of these 3 vaccines over the others. 

Overall, there was evidence of benefits favoring HD-IIV over SD-IIVs. The most evidence was 

available for high-dose vaccine. There were fewer studies and no RCTs including laboratoryconfirmed influenza for adjuvanted vaccines. There were the fewest studies for RIV overall. 

There was no strong evidence favoring one EIV over others among studies providing direct 

comparisons of these vaccines to one another. Limitations include overall few RCT data 

representing few influenza seasons, and no data reflecting the currently available formulations 

of HD-IIV and aIIV. All of the data reviewed regarding those 2 vaccines by this measurement 

reflect the trivalent formulation of the vaccine. Both of those vaccines are now available in 

quadrivalent formulations only. However, pre-licensure studies generally have indicated similar

immunogenicity and safety of quadrivalent vaccines and their trivalent counterparts.

Discussion Summary

Dr. Loehr called everyone’s attention to the amount of work that went into this GRADE review 

over the last 2 years in terms of the approximately 3,500 full text reports assessed and the 

number of studies that actually were included in the analysis of 49. With no disrespect to other 

WGs, in a later study they would hear that the full text assessed were 60 to 100 and 7 were
ACIP Meeting Summary February 23-24, 2022 

29

included in the analysis. The amount of work by Dr. Grohskopf over the last several weeks to 

develop it into a presentable fashion for the ACIP has been outstanding.

Dr. Lee agreed and added that if they all were in a room together, they would give Dr.

Grohskopf a round of applause.

HEPATITIS VACCINE

Session Introduction

Dr. Kevin Ault (ACIP, WG Chair) introduced the hepatitis vaccine session, reminding everyone 

that universal adult hepatitis B (HepB) vaccination was approved in 2021; FDA approved 

PreHevbrio, a 3-antigen HepB vaccine, in 2021;11 and ACIP heard a presentation by the 

manufacturer on the safety and immunogenicity of PreHevbrio on January 12, 2022. The focus 

of this session was PreHevbrio for adults, including EtR and GRADE. Subsequent WG terms of 

reference will include exploration of preferential use of HepB vaccines among specific risk

groups. 

PreHevbrio for Adult HepB Vaccination: EtR and GRADE

LCDR Mark K. Weng, MD MSc (CDC/NCHHSTP) discussed PreHevbrio for adult HepB 

vaccination and presented the WG’s modified EtR and GRADE. The policy question was, 

“Should PreHevbrio be recommended as an option for adults recommended for hepatitis B

(HepB) vaccination?” In terms of the PICO, the population is adults ≥18 years of age. The

intervention is 3 doses of PreHevbrio over 6 months. The comparison is existing HepB vaccines 

licensed for adults in the US (TWINRIX, Engerix-B, Recombivax-HB, HEPLISAV-B).12 The

outcomes considered included HepB virus infection (Critical), SAEs (Critical), and mild AEs 

(Important but not critical). Persons on hemodialysis, pregnant persons, or persons who were 

breastfeeding were not discussed in this EtR Framework. The safety and effectiveness of

PreHevbrio have not been established in adults on hemodialysis. In addition, there are no 

adequate and well-controlled studies of PreHevbrio in pregnant women. Available human data 

on PreHevbrio administered to pregnant women are insufficient to inform vaccine-associated

risks in pregnancy. Data are not available to assess the effects of PreHevbrio on the breastfed 

infant or on milk production or excretion.

In terms of background, PreHevbrio is a mammalian cell-derived, alum adjuvanted, 3-dose 

HepB vaccine. The previously approved Engerix-B and Recombivax-HB are 3-dose vaccines as 

well. Heplisav-B approved in 2018 is adjuvanted with CpG 1018 and is a 2-dose single antigen 

vaccine. In 2021, ACIP approved universal HepB vaccine recommendations for adults 19-59 

years of age as reflected in the 2022 Adult Immunization Schedule published the previous 

Friday, February 18, 2022. An additional HepB vaccine that is safe and non-inferior to existing 

ACIP-approved HepB vaccines could be a beneficial adjunct in achieving the HHS goals of 

eliminating HepB as a public health threat in the US by 2030.

The literature search identified 4,148 initial records of which 1,660 were duplicates. After title 

and abstract review, 64 records remained for full text review. Of these, 57 records were 

excluded due to a variety of reasons (e.g., duplicate studies with different titles, studies on 

non/hypo responders, single arm studies, studies with different schedules/doses of vaccine, 

11 https://www.fda.gov/vaccines-blood-biologics/prehevbrio 12 Studies that were ultimately included used only Engerix-B out of this list of possible comparators.
ACIP Meeting Summary February 23-24, 2022 

30

review articles, clinical trial registries with no results, studies with vaccine that was not of 

interest, dose response studies, lot-to-lot consistency studies, vertical transmission studies, 

therapeutic vaccination, patients with end stage renal disease). In total, 7 RCT studies were 

ultimately included in the GRADE assessment. Despite the PICO question specifying all US 

licensed HepB vaccines as comparator vaccines, the 7 included studies that were found to meet

the criteria had only Engerix-B as a comparator vaccine out of all possible comparator adult 

HepB vaccines licensed in the US.

In terms of the GRADE summary of findings based on those 7 studies presented during this 

session, it is important to note that the GRADE process requires pooling across all available 

studies and uses an intention-to-treat (ITT) approach rather than per-protocol analysis; the data

were not stratified by age group; and all studies considered seroprotection as anti-HB antibody 

≥10 mIU/mL, which is a widely used surrogate marker for prevention of HepB infection. This 

table summarizes the GRADE assessment for all 3 outcomes of interest: 

For HepB infection assessed via seroprotection, 7 RCTs were included. In the pooled analysis 

of these studies, 83.7% of participants achieved seroprotection in the PreHevbrio group as 

compared to 76.7% in the comparison group of single antigen vaccine, which ended up being 

Engerix-b for all included studies. The relative risk was 1.07. However, the risk of bias was

serious as 3 of the 7 studies contributing 60% of the weight to the analysis had high risk of bias 

due to unclear randomization methods or lack of allocation concealment and blinding.

Inconsistency was rated as serious. I2 being 89% suggests substantial heterogeneity. The 

indirectness was not serious for the use of seroprotection with antibody level ≥10 mIU/mL as a 

standard measure of the outcome of HepB infection. This brought the certainty of evidence to 

low (Level 3). For SAEs, 7 studies were included of which 4 reported no SAEs in either 

PreHevbrio or the comparator arm. The pooled analysis showed a relative risk of 1.62 with 

broad interval of 0.50-5.22. The 95% confidence interval cannot exclude the possibility of no 

meaningful difference, which brought serious imprecision into account. The SAEs in the

PreHevbrio group were higher at 2.2% compared to the Engarix0-B group at 1.3%. The risk of 

bias was serious for unknown randomization method or lack of allocation concealment and 
ACIP Meeting Summary February 23-24, 2022 

31

blinding. This brought the certainty of evidence to low (Level 3). Data for mild AEs was 

abstracted from 4 studies, with and overall risk ratio of 1.09 with the PreHevbrio group showing

a higher proportion of participants reporting mild AEs, as compared to the single antigen 

comparator group with imprecision. With I2 equal to 89%, the inclusion of studies at risk

of bias may contribute to the heterogeneity observed and serious inconsistency. This made 

overall certainty low (Level 3) for the outcome of mild AEs. 

In terms of the benefits and harms conclusions from GRADE, the evidence suggests that the 

seroprotection conferred by PreHevbrio is non-inferior (little or no difference) compared with 

seroprotection conferred by Engerix-B. That evidence was established through ITT analysis. 

PreHevbrio may result in little to no difference in SAEs when compared with those resulting from 

Engerix-B. PreHevbrio may result in little to no difference in mild AEs when compared with

those resulting from Engerix-B. 

The WG concluded that the prevention of HepB is a problem of public health importance. The 

WG concluded that for prevention of HepB infection as measured by seroprotection, the

difference in desirable anticipated effects of PreHevbrio compared with those of Engerix B are 

minimal. The WG judged the differences in undesirable anticipated effects between PreHevbrio 

and Engerix B to be minimal for the outcomes of SAEs and mild AEs. The WG judged the 

balance between desirable effects and undesirable effects to favor both PreHevbrio or EngerixB. The WG deemed the overall certainty of evidence for the critical outcomes to be probably not 

important. The WG judged the impact of PreHevbrio compared to Engerix-B on health equity to 

probably have no impact. Based on similarities to the dosage schedule, adjuvant, and vaccine 

mechanism, the WG perceived the domains of values, acceptability, resource use, and 

feasibility for PreHevbrio to be comparable with the values, acceptability, resource use, and 

feasibility of previously approved 3-dose comparator vaccines, which included Engerix-B. 

Based on EtR considerations, the balance between PreHevbrio and currently used HepB

vaccines is closely balanced. Therefore, the WG judgment on adding PreHevbrio as an option 

for HepB vaccination of adults was that the desirable consequences clearly outweigh 

undesirable consequences in most settings. The ACIP Policy Statement for PreHevbrio is:

Discussion Summary

Dr. Long observed that for the EtR Framework, the first question pertained to whether the 

burden of disease is significant, to which the WG answered “yes.” She inquired as to whether 

this could be interpreted to mean if there were no other vaccines available. If there are 4 or 5 

HepB vaccines available, there does not seem to be an unmet clinical need at the moment for 

more HepB vaccines.
ACIP Meeting Summary February 23-24, 2022 

32

Dr. Wharton responded that in this circumstance in which PreHevbrio is an additional vaccine 

for indications upon which ACIP already voted, the public health problem domain of the EtR was

not necessary to address because the ACIP already weighed in on HepB as a public health 

problem, as reflected in the recent vote by the committee to recommend HepB vaccination for 

all adults.

Dr. Ault added that there are 20,000 new HepB cases every year, with $1 billion spent on HepB

and about 2 million Americans living with HepB. 

Dr. Poehling requested clarification on whether ACIP was intended to vote on this new vaccine, 

recognizing that it would be included in the same recommendation as the other HepB vaccines.

Dr. Wharton clarified that given the existing ACIP recommendations for vaccination of adults to 

prevent HepB, the similarity of this product in usage to other licensed products, and the fact that 

it would not be added to the Vaccines For Children (VFC) program, no vote would be 

necessary. However, they did want to have public discussion and as documents are updated,

this vaccine will be included as an available/acceptable vaccine to use for prevention of HepB in 

the US.

Dr. Fryhofer (AMA), speaking as an individual practicing physician, recalled that Slide 21 from 

the December 21, 2021 ACIP presentation from the manufacturer was titled, “Improved 

immunogenicity in key high-risk groups and investigator-initiated studies" and it specifically 

mentioned end-stage renal disease (ESRD), human immunodeficiency virus (HIV), and non- or 

low-responders. She inquired as to whether that type of nuance would be included in guidance 

regarding this vaccine. 

LCDR Weng responded that the WG assessment of the EtR and GRADE question he presented 

included generally healthy populations. Special populations were excluded from this study. The 

next term of reference the WG will examine will include some of the populations Dr. Fryhofer 

mentioned.

MEASLES, MUMPS, RUBELLA (MMR) VACCINE WORKGROUP

Session Introduction

Ms. Lynn Bahta (ACIP WG Chair) introduced this session with a brief background of measles, 

mumps, rubella (MMR) vaccination in the US. High MMR vaccination coverage has been the 

major contributor in the US in the elimination of measles in 2000 and rubella in 2004, and a 

more than 99% reduction in mumps cases. Measles and rubella remain endemic in many parts 

of the world and mumps is still endemic worldwide. These viruses continue to cause locally

acquired and importation-related cases and outbreaks. Between 2016-2021 in the US, data 

have shown that there have been between 13 to 1,282 cases of measles, between 154 to 6,366

cases of mumps per year (primarily locally acquired), and less than 10 cases of rubella per year

(all imported). Currently, there is only 1 licensed MMR vaccine in the US, M-M-R II®

manufactured by Merck.
ACIP Meeting Summary February 23-24, 2022 

33

The ACIP MMR Vaccine WG was established to evaluate the safety and immunogenicity of a 

new candidate MMR vaccine PriorixTM manufactured by GlaxoSmithKline (GSK). The MMR 

Vaccine WG first met in in January 2022. This WG includes 17 members comprised of ACIP 

voting members, liaisons, ex officios, and CDC experts who represent a broad range of 

expertise (e.g., epidemiology, vaccine safety, infectious diseases, general medicine, pediatrics, 

vaccine administration/delivery, public health/surveillance, communications). The WG’s Terms 

of Reference (TOR) are to consider the policy topic of the equivalency and usage of the new 

MMR vaccine (PriorixTM, GSK) compared to the currently licensed MMR (M-M-R II®, Merck). 

Planned WG activities are to:

 Review the safety and immunogenicity data for the new and currently licensed MMR 

vaccines

 Adjudicate non-inferiority of the vaccine candidate compared to the currently licensed MMR 

vaccine

 Consider the new vaccine’s use for licensed indications and existing ACIP 

recommendations for the prevention of measles, mumps, and rubella

 Consider concomitant use with other childhood vaccines

 Consider interchangeability of use in the MMR vaccine series

 Develop MMR vaccine policy options that ACIP may consider for recommendation

This session included a presentation of the data by GSK on the safety and immunogenicity of 

PriorixTM compared to M-M-R II®. Between now and the June 2022 ACIP meeting, the WG will 

convene monthly meetings and additional meetings as needed to use the EtR Framework to 

assess the available evidence. During the June 22-23, 2022 ACIP meeting, the WG will present 

policy options for consideration by the full ACIP. During that meeting, there will be a possible 

vote if determined to be necessary and if this candidate MMR vaccine is licensed by FDA. ACIP 

members were requested to consider the following questions during this session:

 Do the data presented today support the equivalency of these two vaccines?

 What additional data would you like to see to consider equivalency and interchangeability?

MMR Safety and Immunogenicity

Dr. Remon Abu-Elyazeed (GSK) presented an overview of GSK’s MMR vaccine. The GSK 

MMR vaccine was first licensed in Germany in 1997 under the trade name PriorixTM. It is 

currently licensed in more than 100 countries worldwide, including all European countries, 

Canada, and Australia. Over 400 million doses have been distributed worldwide. GSK submitted 

a Biologics License Application (BLA) to FDA in June 2021. The FDA Action Date is June 2022. 

For FDA registration, the GSK Clinical Development Program demonstrated that PriorixTM is

well-aligned with the ACIP recommendations for M-M-R II® in that it had a non-inferior immune 

response, comparable safety, and can be used interchangeably in individuals who previously 

reviewed M-M-R II® or ProQuad®. 

The proposed indication for PriorixTM under FDA review is active immunization for the 

prevention of measles, mumps, and rubella in individuals aged 12 months and older. The 

proposed dose is 0.5-mL by subcutaneous injection. The first dose is administered at 12 to 15 

months of age and the second dose at 4 to 6 years of age. The second dose may be

administered before age 4 provided that there is a minimum interval of 4 weeks. For catch-up, 

the second dose may be administered at 7 years of age and older.
ACIP Meeting Summary February 23-24, 2022 

34

The development plan in support of the BLA consisted of 1 Phase II and 5 Phase III studies.

The Phase III studies enrolled over 16,000 subjects, approximately 50% of whom were enrolled 

in the US. The 5 Phase 3 studies included subjects aged 12-15 months (Studies 160, 161, 162), 

subjects aged 4-6 years (Study 158), and subjects aged ≥7 years (Study 159). Studies 158, 

159, and 160 assessed the immunogenicity, safety, and non-inferiority of PriorixTM at the least 

potency for the US compared to M-M-R II®. Study 160 also demonstrated manufacturing lot-tolot consistency. The immune response at the end of shelf-life potency was demonstrated in 

Study 161, and the maximum potency was assessed in Study 162. In terms of the demographic 

characteristics for all aggregated studies for the total vaccinated cohort, the demographic profile 

of the study participants is representative of the ethnically diverse US population and was 

similar between those who received PriorixTM and M-M-R II®. 

Dr. Abu-Elyazeed presented the safety evaluation of PriorixTM post-Dose 1 children aged 12-15 

months; post-Dose 2 in children aged 12-15 months who received a second dose 6 weeks after 

the first dose; post-Dose 2 in children aged 4-6 years; and post-Dose 2 in individuals aged 7 

years or older who received PriorixTM. All trials assessed the safety endpoints shown in the 

following table among children and adults receiving 1 or 2 doses of PriorixTM:

Study 160 was an observer-blinded, non-inferiority, control study in which subjects aged 12-15 

months received a first dose PriorixTM or M-M-R II® administered concurrently with US licensed 

vaccines. The frequency of reported solicited, local, and general AEs was similar in both groups.

The most frequently reported solicited local AE in both groups was injection site pain at 26% in 

PriorixTM and 28% in M-M-R II®. Irritability was the most frequently reported general AE at 63% 

in PriorixTM and 66% in M-M-R II®. In Study 161, an observer-blind controlled clinical study

clinical study, subjects aged 12-15 months received a first dose of PriorixTM or M-M-R II® 

followed by a second dose of the same vaccine 6 weeks later. Post-Dose 2, the frequencies of 

reported solicited local and general AEs were similar in both groups and were slightly lower

than those reported after the Phase II study. 

A subset of subjects was evaluated for local and general AEs in Study 158, an observer-blinded

controlled study. In this study, subjects aged 4 to 6 years received PriorixTM or M-M-R II® as a 

second dose. These children had received an initial dose of M-M-R II® or ProQuad® in the 

second year of life. In this sub-cohort, the reactogenicity was similar between the PriorixTM and 

M-M-R II® groups. The most common solicited local AE was pain at the injection site of 41% in 

both groups. The most common solicited general AE between Day 0 and Day 42 was fever at 

24% in the PriorixTM group and 25% in the M-M-R II® group. In study 159, subjects aged 7 years 

and older received PriorixTM or M-M-R II® as a second dose following pre-administration of a 
ACIP Meeting Summary February 23-24, 2022 

35

combined MMR-containing vaccine. The reactogenicity profile was similar between the 2 

vaccine groups.

Turning to the immune response data, in agreement with FDA pre-defined endpoints, PriorixTM 

would infer immunity based on the comparative immunogenicity data with M-M-R II®. In study 

160, children aged 12-15 months received a first dose of PriorixTM or M-M-R II® concurrently 

with hepatitis A (HepA) vaccine and varicella vaccine. Children enrolled in the US also received 

PCV13 vaccine. The predefined non-inferiority success criteria of the first dose of PriorixTM 

compared with M-M-R II® were demonstrated in terms of seroresponse rates and antibody 

geometric mean concentrations (GMCs) to MMR antigen. In study 161, subjects aged 12-15 

months received a first dose of PriorixTM or M-M-R II® followed by a second dose of the same 

vaccine 6 weeks later. In a descriptive analysis in a subset of subjects, the immune response 

after the second dose was similar between the 2 groups in terms of seroresponse rate, 

antibodies, and GMC for all antigens. 

In study 158, subjects 4-6 years of age received PriorixTM or M-M-R II® as a second dose after 

an initial dose of M-M-R II® or ProQuad® in the second year of life. PriorixTM and M-M-R II® were 

given concurrently with DTaP-IPV (diphtheria, tetanus toxoids and acellular pertussis and 

inactivated poliovirus vaccine) and varicella vaccines in a subset of subjects. The pre-defined 

non-inferiority criteria were met for seroresponse rate and antibody GMC for all antigens. 

In study 159, subjects aged 7 years and older received PriorixTM or M-M-R II® as a second dose 

after previous administration of a combined MMR vaccine. The pre-defined non-inferiority 

criteria were met for all comparisons.

Interchangeability with other MMR-containing vaccines is an important clinical consideration. In 

the development plan, GSK studied the use of PriorixTM after a previous dose of other MMR 

vaccines. Based on the comparable immunogenicity data in primed subjects who received 

either MMR vaccine in Studies 158 and 159, PriorixTM can be administered interchangeably with 

other MMR vaccines received as the first dose. Concomitant use of PriorixTM was evaluated with 

other routinely administered vaccines including HAVRIX, varicella vaccine, and PCV13 in Study 

160 in children aged 12-15 months and KINRIX and varicella vaccine in Study 158 in children 

aged 4 to 6 years. There was no evidence that PriorixTM interfered with the antibody responses

to the antigens in the previously mentioned vaccines compared with immune the responses of 

M-M-R II® co-administered with these same vaccines.

ACIP recommends MMR vaccination of children as young as 6 months of age in an outbreak

setting or prior to international travel. With that in mind, Dr. Abu-Elyazeed shared the results of 2 

open-labeled, randomized, controlled Phase III studies conducted in Singapore and India.13

These studies evaluated the immunogenicity and safety of 2 doses of PriorixTM co-administered 

with 1 or 2 doses of the GSK varicella vaccine, Varilrix® in healthy infants beginning at 9 months 

of age. The seroconvergence rate after 1 dose for measles was in the range of 88% to 94% for

measles, 83% to 92% for mumps, and 100% for rubella. Nearly all children (> 99%) 

seroconverted for all antigens after completing the 2-dose vaccination schedule in both studies.

The 2 studies concluded that PriorixTM was well-tolerated and immunogenic when administered

to children as young as 9 months and 12-15 months of age.

13 Goh P, Lim FS, Han HH, et al. Infection. 2007;35(5):326-333. http://dx.doi.org/10.1007/s15010-007-6337-z; and Lalwani S, 

Chatterjee S, Balasubramanian S, et al. BMJ Open. 2015;5(9):e007202. http://dx.doi.org/10.1136/bmjopen-2014-007202. 
ACIP Meeting Summary February 23-24, 2022 

36

To summarize the GSK conclusions regarding the safety of PriorixTM, the overall safety data 

collected during PriorixTM development have not identified a safety concern and are comparable 

to the safety profile of M-M-R II®. PriorixTM is generally well-tolerated in subjects 12-15 months 

of age, 4-6 years of age, and ≥7 years of age given as a first or a second dose. The safety 

provides of PriorixTM co-administered through the range of routine childhood vaccinations is 

comparable to that of the M-M-R II® co-administered with the same vaccine. The safety profile of 

PriorixTM, including at the maximum release potency, is acceptable and comparable to the 

safety profile of M-M-R II®. 

In addition, safety surveillance of PriorixTM outside of the US showed no significant safety 

concerns and confirmed an acceptable safety profile consistent with the US registration studies.

In summary of the GSK conclusions in regard to the immunogenicity of PriorixTM, the clinical trial 

data demonstrated non-inferiority of the immune responses of PriorixTM compared to M-M-R II®

in terms of seroresponse rate and GMCs in children 12-15 months of age after a single dose

and in children 4-6 years and individuals ≥7 years of older when PriorixTM is given as a second 

dose of MMR vaccine. The data supports the dosing schedule recommended by ACIP for MMR 

vaccination. PriorixTM can be administered interchangeably to individuals who received a

previous vaccination with M-M-R II® or ProQuad®. PriorixTM can be co-administered with routine 

US pediatric vaccines.

In conclusion, the GSK MMR vaccine program has met the development objectives to bring 

PriorixTM to the US market. From a public health perspective, the availability of a second MMR 

vaccine would be efficient. 

Discussion Summary

Dr. Lee expressed gratitude to GSK for enrolling people at-risk in the clinical trials.

Dr. Daley requested additional information about the term “meningism including 

febrile seizure” that appeared on several slides in this presentation. In addition, he noted that 

there were several fibral seizures and wondered whether those were characteristic of what is 

typically observed following M-M-R II® at 7-10 after vaccination. 

Dr. Abu-Elyazeed explained that this refers to meningeal irritation and could include headache, 

stiff neck, blurring of vision, and/or convulsion. None of the children were diagnosed with 

meningitis. Fibral seizures were reported as part of meninge irritation within 43 days following 

each vaccination and there were very few. Among children 12-15 months of age, 16 cases were 

identified out of 6,441 (0.25%) in the PriorixTM cohort and 7 cases out of 3,361 (0.2%) in the MM-R II® cohort. Only 5 of the 16 cases (0.08%) were related in the PriorixTM cohort and 5 of the 

7 cases (0.14%) were related in the M-M-R II® cohort.

Dr. Daley asked whether there are any estimates of the rate of vaccine-associated fibral 

seizures following PriorixTM from post-authorization studies elsewhere in the world, and related 

to that whether there are any estimates of the rate of thrombocytopenia following PriorixTM given 

post-authorization elsewhere in the world. 

Dr. Abu-Elyazeed replied that while he did not have any febrile seizure information in hand, 

there were no cases of thrombocytopenia following PriorixTM and only 1 case out of 3,395 in the 

M-M-R II® cohort, representing 3/10,000.
ACIP Meeting Summary February 23-24, 2022 

37

Ms. McNally asked whether there was any difference in reactogenicity when PriorixTM is coadministered or used interchangeably, and how this vaccine might be examined in a younger 

age group for co-administration with COVID-19 vaccine. 

Dr. Abu-Elyazeed indicated that this program started in 2008 and all clinical trials were 

completed in 2014 before COVID-19, but GSK would consider a study on the co-administration

of PriorixTM with COVID-19 vaccine if ACIP wishes them to do so. In terms of reactogenicity 

when PriorixTM is co-administered or used interchangeably, there was no difference in AEs 

between the groups who received PriorixTM or M-M-R II® (Slide 8). For interchangeability, the 

safety profiles in subjects who received either PriorixTM or M-M-R II® following a previous dose

showed no difference.

Dr. Kotton observed that there has been limited research over the years in transplant and other 

immunocompromised pediatric patients to show that it is safe for them, when on very low dose 

immunosuppression, to receive the current MMR vaccine. She asked whether GSK is studying 

this and if there is any way of knowing whether this would be similar with PriorixTM. 

Dr. Abu-Elyazeed responded that PriorixTM has a comparable safety profile to M-M-R II® and 

can be used in the same way. However, GSK does not have specific data on

immunocompromised pediatric patients. 

Regarding the Singapore study, Dr. Sanchez asked whether the mothers had received previous 

vaccination with MMR vaccine or if they had natural infection previously. For the post-Dose 1 

and post-Dose 2 data, he inquired as to whether there were data for baseline MMR titers. The 

role of maternal antibody was somewhat confusing as presented in terms of the effects of these 

titers.

Dr. Abu-Elyazeed said he would have to review the data again for the studies in Singapore and

India to determine whether data were collected from the mothers. The definition used for the 

“seropositive response rate” was the percentage of initially seronegative subjects with 

concentration above the seroresponse threshold for each antigen. The seroresponse threshold 

for measles was 200 mIU/mL, for mumps 10 enzyme-linked immunosorbent assay units 

(EU)/mL, and for rubella is 10 international units (IU). Those with positive MMR titers were 

excluded from the analysis.

Dr. Cineas asked whether there are any studies of the use of PriorixTM in adults who are not 

immune to 1 of the 3 components for adults in other countries. 

Dr. Abu-Elyazeed noted that the indication GSK is seeking from FDA, which is under approval, 

is among individuals aged 12 months and older and for catch-up in older populations. Study 159 

included individuals ≥7 years of age. About 36% of the subjects were aged 7-17 years 64 of the 

subjects were about 18 years of age and older. 

Dr. Long recalled seeing the maximum potency in parentheses and asked whether she 

understood that the same dose was used in all of the studies, and Dr. Daley asked whether it 

was that potency varies lot-to-lot or that they tried a higher dose. 

Dr. Abu-Elyazeed indicated that in terms of the maximum dose, licensure the US requires the 

minimum and maximum potency required to be immunogenic to be defined. The maximum dose 

must be safe. Only Study 162 assessed maximum potency and had safety as a primary 

objective. It is not that potency varies lot-to-lot. They tried higher doses to ascertain the 

maximum potency necessary to ensure that the dose is sufficient at the end of shelf-life. There 
ACIP Meeting Summary February 23-24, 2022 

38

was a wide range from the minimum to maximum potency in this development program. The 

minimum is defined as end of shelf-life and the maximum is the least potency necessary to 

ensure that at the end of shelf-life, the potency of the antigen is sufficient. Through this 

development program, for measles the minimum potency was 3.4 log10 CCID50 and the 

maximum was 4.5 log10 CCID50. For mumps, the minimum was 4.2 log10 CCID50

and the maximum was 5.7 log10 CCID 50. For rubella, the minimum was 3.3 log10 CCID50

and the maximum was 4.4 log10 CCID50.

Dr. Long observed that only about 1,000 children received the maximum potency. Febrile 

seizures are not reported spontaneously following receipt of MMR vaccine because they do not 

occur within a week of vaccination. The recipient has to grow the virus and get the febrile illness 

that results in the febrile seizure, which occurs in the second week. Parents and doctors do not 

always associate this with vaccination. The incidence is about 1/1,800 and vaccine-associated 

febrile seizures are often not identified until studying this prospectively. The numbers Dr. AbuElyazeed reported of 1/500 and 1/300 were very high. It did not appear that there was a single 

study with just MMR vaccine. All were with concurrent administration with 2 or 3 other vaccines 

that could cause fever and seizures at completely different times. She would like to know the 

difference in the incidence of seizures depending on what was received concurrently. With only 

a couple of thousand children in the febrile seizure age range, combined with meningism and 

febrile seizures that are not the same kinds of events, it was surprising that febrile seizures

associated with MMR were not expected to occur at nearly the same frequency with the second 

dose because the second dose is usually only picking up the 5% or 6% percent who were 

missed from the first dose. There is robust virus replication in 7% of the population, so it is 

important to understand what is the same and different.

Dr. Abu-Elyazeed referred to Slide 9, the second dose in children aged 12-15 months. Fever 

was 32.5% and grade three is 3.5% among PriorixTM recipients and 34.3% among M-M-R II®

recipients, or basically no difference. Meningism, including febrile convulsions increased up to 

43 days post-vaccination. He can present to ACIP the AEs related to meningism, fever, and 

fibral convulsion in each of the studies.

Dr. Long said she would like to see febrile convulsions in the second week following 

immunization and in the first 48 and 72 hours separately since a lot could be going on early on 

that would wash out any potential differences that might be occurring in the second week.

PUBLIC COMMENT

Overview

The floor was opened for public comment on February 23, 2022 at 2:25 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 issuefocused 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-2022-0022. 

Visit http://www.regulations.gov for access to the docket or to submit comments or read 

background documents and comments received.
ACIP Meeting Summary February 23-24, 2022 

39

Public Comment 

Ms. Leah Russin

Co-Founder/Executive Director

Vaccinate California

Thank you for your time. I know COVID isn’t on the agenda for today, but as the parents of a 21-

month-old child in the vaccine trial, I want to take a moment and acknowledge the confusion and 

frustration that we parents are feeling. I have 2 main points, both related to messaging and both 

of which actually relate to your MMR discussion today. First, when explaining the vaccine 

approval process, “because that’s how we’ve always done it” isn’t good enough. Explain what 

was considered, why it was rejected, and what’s next. Please think as creatively as a scared

parent in considering options that need explanation. For example, back in December, Pfizer’s 

first press release indicated that data was strong for 2 doses of 3 microliters for toddlers but not 

for ages 2 to 5. Why couldn’t we have considered authorizing the 2-dose series for toddlers

before preschoolers back in December allowing us to have protected at least some of our 

children through Omicron? “Because that’s not the way we do things” isn’t a good enough

answer. Also, why couldn’t Pfizer have trialed a 5 microliter 2-dose series in addition to adding a 

third dose of 3 microliters? Two vaccines is already asking a lot for families. Again, “because 

that’s not how we do things” isn’t good enough. Explain to us why. Don’t leave us fumbling

around in Facebook groups and WhatsApp chats with hundreds of other parents trying to figure 

out why what seems obvious to us isn’t happening. Second, many physicians and other medical 

practitioners report that there’re uncomfortable and lack confidence discussing vaccines with 

their patients. You are the experts. You have uniquely delved deep into the data and carefully 

assessed and weighed the risks of the diseases against the vaccine. I encourage you when you 

do recommend a vaccine for approval have staff take the time to prepare materials for public

dissemination reflecting your collective comments explaining why you personally recommend 

the vaccine. Your comments during and after voting are often eloquent and compelling, but

they’re inaccessible to medical professionals that ultimately might benefit from your experience 

when discussing vaccines with their patients. In honor of Paul Farmer, please continue to push 

for equitable and easy access for healthcare for all. Thank you again for your time and your 

service to public health.

Ms. Sarah Barry 

Independent Pro-Vaccine Advocate

Hello and thank you ACIP. My name is Sarah Berry and I’m an independent pro-vaccine 

advocate. Because these meetings are well-attended and listened in by anti-vaccine activists, I 

think it’s very relevant to talk about attitudes towards vaccines in general and I’m going to read 

off a comment that an anti-vaccine activist made about me in regard to past public comments I 

have made to ACIP. “Sara is insane. Every chance she gets she goes on about how parents

abuse their autistics by trying to help them in any ways possible. We should just accept them 

and their suffering as normal. It’s absolutely disgusting.” I mention this comment because it is 

clear evidence that anti-vaxxers are incapable of adequately defending themselves from my 

specific form of criticism. And I need not just ACIP, but every pro-vaccine person in the world, to 

know this. I have indeed given public comments to ACIP about the dangerous and yes abusive

cures for autism that anti-vaxxers have created. Since the person who called me insane clearly 

did not listen to the facts that I have shared in previous public comments, I will go over some of 

them again because again, this is something the anti-vaxxers are scared of and that’s important 

when we talk about vaccines. First, Kerri Rivera. She sold a book called “Healing the Symptoms 

Known as Autism.” A careful review of her book shows it is a manual that teaches parents how
ACIP Meeting Summary February 23-24, 2022 

40

to force their children to drink bleach. Other methods in the book detail how to give bleach baths 

and even bleach enemas. Second Mark Geier. He lost his medical license for experimenting on 

autistic children by giving them dangerously high doses of a drug called Lupron. To get approval 

for his experiment, he created and oversaw an Institutional Review Board along with his son,

his wife, and other associates. It’s an obvious breach of basic medical ethics and if any vaccine 

manufacturer attempted such a thing, anti-vaxxers would rightly use it as an example of

corruption. When it’s one of their own, however, they look away. Lastly, Andrew Wakefield.

Whenever anybody says his name, I want the next sentence to be about what happened to Jack 

Piper. If you don’t know about Jack Piper, I will tell you. As per Wakefield’s experimental

protocol, Jack Piper was subjected to a colonoscopy that ended up piercing his bowel 12 times.

He was 5 years old and had to stay in intensive care for 2 weeks. He also suffered multiple

organ failures and even developed epilepsy. Even so, Andrew Wakefield is still a hero to the

anti-vaccine community. Two of the biggest anti-vaccine voices are Robert F. Kennedy, Jr. and 

Del Bigtree. When it comes to people like Kerri Rivera and Mark Geier, I challenge Kennedy 

and Bigtree to think about how they have personally failed to call out the unethical and

dangerous actions I have described today. If my comments calling out this failure are disgusting 

to anti-vaxxers, then so be it. I will not back down because I know that my method of talking

about this situation is the way to solve the anti-vaccine misinformation crisis. Thank you again 

ACIP. 

Dr. Grace Lee

ACIP Chair

Thank you for your comments. I just want to interject for a moment that we are very much 

interested in hearing public comments about the votes. I want to recognize that there are many 

challenges out there with communication and what not. Our preference is to use public 

comments to focus in on the issues at hand and, again, not to focus on individuals as opposed 

to the issues. Thank you very much.

Mrs. Barbara Loeppke

Loeppke Professional Services

Good afternoon, Chairwoman Lee and the Committee. My name is Barbara Loeppke. I’m a 

mother, grandmother, and advocate. Something good has occurred with the COVID vaccine 

and that is that more of the American public has started attending the FDA and CDC meetings 

online and taking an interest in what you do. This also means though that they’re asking more 

questions. I’ve been asked to present a few of those today and perhaps you can address these 

now or in the future. One concern I’ve been told is that adverse events seem to be diluted by the 

listing of redness at the injection site and pain at the injection site as the most common

complaint. This makes other more concerning adverse events get bumped down the list and not 

mentioned. This is something the public expects from the manufacturer, but the public believes

the CDC is working for them and they’d like to know more about the adverse events than just 

the redness caused by the puncture of a needle. As the committee continues to give their

COVID vaccine recommendations in the future, can you tell the public when Comirnaty will 

actually be used in the US? Some were under the impression that they’re getting the actual

licensed product when they’re still getting the emergency authorized version. Is Comirnaty not 

used in the US yet due to the VIPP process? And if it isn’t, when will it be? Have you detected a 

signal on new suicidal ideations from the COVID vaccine? A quick search of VAERS showed

over 900 entries in the report and so far, I don’t believe this has been mentioned in any of the

meetings. Can you tell us how many reports of death from the COVID vaccines are currently 

being held back for review? Could you go through the process in one of the meetings of how a 
ACIP Meeting Summary February 23-24, 2022 

41

vaccine comes before the committee? I think there’s a lot of people that would like to know that 

answer. And finally, just as we can’t give you legal advice about the meetings and shutting down 

a public comment, neither can anyone else who is not a licensed attorney in the US. With more 

of the public attending online each time, it would likely further diminish the image of the CDC, 

and currently in the last couple of days, that’s been diminished with reports that there’s been

data held back. Thank you so much for your time. We appreciate the work you put in and we 

await your responses to a few of the questions the public has.

Marla Dalton, PE, CAE

Executive Director/Chief Executive Officer

National Foundation for Infectious Diseases

Good afternoon. I am Marla Dalton, Executive Director and CEO of the National Foundation for 

Infectious Diseases, or NFID. On behalf of NFID, as a longstanding partner CDC, we appreciate 

the valuable work of ACIP in guiding US immunization policy and protecting public health

through the ongoing review and analysis of vaccine safety and efficacy data. Recommended 

vaccines help protect individuals of all ages from serious diseases including flu, pneumococcal 

disease, hepatitis B, and measles among others. And although annual flu vaccination is 

important for everyone age 6 months and older, adults aged 65 and older are at greater risk of 

flu-related complications, including hospitalization and death. Yet, despite the availability of safe 

and effective vaccines to help prevent disease, immunization rates remain suboptimal across 

populations for nearly all recommended vaccines in the US. This problem has only been 

exacerbated by the COVID-19 pandemic, with routine vaccinations declining significantly across 

all age groups. These declines are dangerous to public health. We can no longer delay lifesaving vaccines and we must address the concerning decline in vaccination rates. Low

immunization rates contribute to poor health outcomes and they carry a high price tag for 

society as a whole. The US spends an estimated $26.5 billion annually treating adults

with flu, pneumococcal disease, shingles, and pertussis. NFID urges additional action to ensure

that all populations are vaccinated as recommended. We must work together to help protect 

individuals and society as a whole. It is not enough to have safe and effective vaccines. We 

must ensure these vaccines are used as intended. Thank you all for the important work you do 

to protect public health and for your tireless and dedicated service.

Ms. Clarissa Garcia

Executive Portfolio Lead

Patient Education Programs

American Heart Association

I’m Clarissa Garcia, our Executive Portfolio Lead for Patient Education Programs. On behalf of 

the American Heart Association (AHA), I welcome this opportunity to publicly share comments 

with the ACIP. The COVID-19 pandemic has affirmed that chronic diseases and infectious 

diseases are inextricably linked. We offer these comments about recommendations to 

strengthen influenza vaccination guidance as essential for protecting health and preventing 

adverse outcomes equitably. In El Paso Texas, we observed lower than average influenzarelated hospitalization rates, in part due to our CDC funded outreach efforts over the past 2 

seasons. We believe decreased rates were a direct result of a mix of the following: Consumer 

and healthcare professional education and mobilization, community access, the distribution of 

high-dose influenza vaccine, and COVID-19 mitigating measures such as mask wearing and 

social distancing. The AHA supports operationalizing the Vaccine for Adults program that is a 

federally funded, nationwide, evidence-based adult vaccination program in the United States. 

The program focuses on vaccinating under-served racial and ethnic communities, Medicaid 
ACIP Meeting Summary February 23-24, 2022 

42

beneficiaries, and adults aged 65 years or older. Specifically, the AHA supports the availability 

of the high- dose influenza vaccine for seniors during influenza season in hospitals, clinical care 

settings, community pharmacies, and other locations that get vaccines to people. The AHA

endorses rapid ACIP reviews of all relevant science related to influenza vaccines—standard and 

high dose. Enhanced availability of high-dose and standard-dose influenza vaccines creates a 

unique opportunity to explore disparities in standard-dose influenza uptake against racial and 

ethnic groups in addition to analyzing the structural and systemic factors affecting access to 

high quality vaccination services. The AHA aligns its recommendations regarding influenza 

vaccine with ACIP recommendations and revises recommendations to align with updates from 

ACIP. The American Heart Association will do its part to improve equitable influenza vaccine 

access and uptake with an emphasis on educating both the consumer and healthcare

professionals. Our message is to administer the most effective influenza vaccine based on age 

and underlying medical condition. We will be submitting more comprehensive written documents

for consideration. I thank you for your time today.

Dorit Reiss, JD 

Professor of Law

University of California

Hastings College of the Law

Thank you. My name is Dorit Reiss. I’m a Professor of Law at the University of Hastings College 

of the Law. Thank you again for the opportunity to comment. You’ve heard a lot about issues 

and messaging, so I want to start by saying that one of the good things about this committee is 

the high-level transparency where the data good or bad is presented in such transparent ways. 

To give just one example of the many wonderful presentations we’ve seen today, the careful 

examination of the studies and the comparative assessment of vaccines involve not just the 

clear discussion of the data, but also the limitations of it. And that’s been true throughout. So, I 

know your committee and its staff work really hard to make data accessible and transparent, 

and I know you came up with some creative great ideas, for example your previous illustration 

of the benefits of influenza vaccine. And I wanted to thank you for your efforts with

transparency. I appreciate them and I know a lot of people do. I also want to remind the 

committee that generally, the people who are subject to your recommendations are lay people 

and won’t come in with a preference between vaccine or an opinion and depend on doctors to 

join you. I want to echo Ms. Russin’s recommendation that some handout or some information 

summary of the wonderful comments made by the committee might be helpful to doctors in 

giving points to people in why they should get this vaccine. I know you have a lot to do. I know 

you’ve done a lot. I would consider whether there’s a way for you to also put out summaries of 

the important points that the committee made in support of a recommended vaccine. I also want 

to echo Dr. Dalton’s points about the importance of emphasizing routine vaccines. And I was 

glad that this meeting gave attention to them, because we know we have a problem. We know 

that COVID that has interrupted our life in so many ways and also interrupted immunization 

rates across the board. And it’s time to put an emphasis on that. And finally, I want to encourage 

you to respond to public comment. As I said in the past, I think you can legally and legitimately 

move through these comments but understand where you’d you hesitate to do this. But if you 

want to preserve oral comments, I want to encourage the committee to post [unclear] advantage

at least for routine meetings. I know that before you’ve made an effort to increase transparency 

by, for example, making sure people are notified about public commenting beforehand and 

putting the agenda up. I appreciate your efforts. I know it’s been a rough 2 years. But putting the 

slides up in advance will help people make the public comments more meaningful. In this case, 

the MMR slides were still not up this morning, so I hope that improves. Thank you again for all 

your work.
ACIP Meeting Summary February 23-24, 2022 

43

THURSDAY: FEBRUARY 24, 2022

AGENCY UPDATES

Centers for Disease Control and Prevention

Dr. Posner presented an update on behalf of CDC. Beginning with staffing announcements, he 

reported that Dr. Rima Khabbaz would be retiring from CDC following 38 years of service. She 

has been the Director of the National Center for Emerging and Zoonotic Infectious Diseases

(NCEZID) for the last 5 years. Upon her retirement at the end of March 2022, Deputy Director, 

Dr. Christopher Braden, will take over as Acting Director for NCEZID. Dr. Althea Grant-Lenzy is 

currently serving as the Acting Deputy Director for Science within NCIRD. In this role, she leads 

special cross-cutting projects that connect and improve the Center’s surveillance, epidemiology,

laboratory, and data science programs and is very involved in the transition activities with the 

response.

In terms of COVID vaccine implementation updates, CDC provides daily updates on COVID-19 

vaccine distribution and administration on the CDC COVID Data Tracker website.14 As of 

February 22, 2022, more than 686 million doses have been delivered, more than 549 doses 

have been administered, and more than 214 million individuals have been fully vaccinated. 

Subsequent to the recommendation for the Pfizer BioNTech COVID-19 vaccine for children 

aged 5-11 years, more than 9.2 million individuals in that age group have received at least 1 

dose of the COVID vaccine. Updated guidance has been posted for the extended intervals to 

the mRNA COVID-19 vaccine primary series. The interim Clinical Considerations are in the 

process of being updated and other CDC web pages and materials reflect this and should be 

updated shortly. 

Moving to current efforts on maintaining childhood vaccination coverage, provider ordering of

publicly purchased vaccine for FY22 has decreased 70% compared to FY19 orders in FY2020. 

Non-influenza vaccine orders decreased by 15% overall, with a significant drop in vaccines 

administered to children and adolescents. Influenza vaccine coverage as of January 8, 2002 for 

children aged 6 months to 17 years is approximately 50%, which is almost 3 percentage points 

lower than the previous season. CDC has developed information for parents and providers, 

such as the Well Child Visit and Recommended Vaccination Communications Campaign15 that 

encourages parents to prioritize the need to catch-up their children on routine childhood 

vaccinations. CDC issued a number of Calls to Action in August 2020, October 2020, and March 

2021 to address decreases in routine childhood immunization to numerous partners, 

immunization programs, and providers.

Seasonal influenza activity resumed in the 2021-2022 season. Influenza activity increased over 

the fall and through the week ending December 25, 2021, but then began to decline. In the last 

week or so, there was a slight increase in influenza activity. Influenza activity is difficult to 

predict, such that influenza may continue to circulate for a number of weeks. The majority of 

influenza virus this season is expected to be A(H3N2). Preliminary data suggest that VE against 

currently circulating A(H3N2) viruses may be reduced this season. However, vaccination still 

likely offers protection—including against serious influenza illness and death. Influenza 

14 https://covid.cdc.gov/covid-data-tracker/#datatracker-home 15 https://www.cdc.gov/vaccines/parents/visit/vaccination-during-COVID-19.html 
ACIP Meeting Summary February 23-24, 2022 

44

vaccination coverage is lower this season compared to last season, especially among certain

higher risk groups such as pregnant people and children. Racial and ethnic disparities persist, 

with lower vaccination rates among non-Hispanic Black adults and Latino adults compared to 

non- Hispanic White adults. Getting an annual influenza vaccine is the best way for people to 

protect themselves, their loved ones, and their communities against influenza. CDC continues to 

recommend influenza vaccination as long as school activities continue. In terms of seasonal 

influenza vaccine distribution for the 2020-2022 season, vaccine manufacturers have projected

that they will provide as many as 188 to 200 million doses of influenza vaccine for the US 

market. As of February 11th, approximately 175 million doses of influenza vaccine have been 

distributed.

Regarding measles and rubella elimination reverification, the Pan American Health Organization

(PHAO) annual meeting of Measles, Rubella, and Congenital Rubella Syndrome Elimination 

Regional Monitoring and Verification Commission took place in November-December 2021. 

Noted declines in surveillance were reported in nearly every country in the region. The decline

in measles and rubella in suspected cases in 2020 was reported as likely being due to 

decreased importations and social distancing, which may lead to a false sense of security in the 

region. The US was verified as sustaining elimination. All countries in the region (including 

Brazil, which lost status in 2019 and Venezuela, which was added to 2018) were certified as 

having maintained measles and rubella elimination. In response to measles among Afghan 

evacuees, the US Government (USG) implemented a rapid response to quickly interrupt 

measles virus transmission among Afghan evacuees in 2021 during Operation Allies Welcome 

(OAW) in which CDC provided immediate guidance for OAW-implementing partners to prevent 

measles transmission among evacuees on a domestic and international basis due to an 

ongoing outbreak and low vaccine coverage in Afghanistan, as well as close living quarters 

during the process of evacuating people into the US. After measles cases were confirmed, a 

CDC directive on September 14, 2021 called for mass vaccination for measles, mumps, rubella, 

and varicella that reached approximately 100% of coverage, followed by a 21-day quarantine 

period. Also called for was a pause in evacuation flights and administration of vaccine for polio 

and COVID-19. This effort limited measles cases to just 47 among the 70,000-plus Afghan 

evacuees without any deaths or community infection. According to preliminary data, a total 49 

measles cases were reported in the 5 jurisdictions in 2014.

Dr. Lee thanked CDC for continuing to manage the unbelievable range of activities and 

responsibilities the agency has. It is important to remember how much CDC is doing to protect 

the health of the population in addition to addressing the pandemic. She highlighted and 

thanked CDC for continually updating the guidance on COVID-19 vaccines, particularly the 

updates on the interval issue. In addition, she expressed congratulations to Dr. Khabbaz and 

extended well wishes to her on behalf of the entire committee. 

Centers for Medicare and Medicaid

Ms. Hance presented the CMS update from the Medicaid perspective. Building on Dr. Posner’s 

comments, she emphasized that CMS also is committed to working to increase immunization 

rates for COVID-19 and influenza vaccines, and appreciates that CDC has made themselves 

available to speak to different groups within CMS. For example, CDC spoke during CMS’s 

recent monthly call with state Medicaid Directors during which they highlighted changes 

pertaining to COVID-19 vaccinations. In January, CDC gave a presentation to the Children’s 

Health Insurance Program (CHIP) State Plan Directors that highlighted COVID-19 vaccines and 

the important need to continue to promote catch-up of pediatric immunizations. CMS will 
ACIP Meeting Summary February 23-24, 2022 

45

continue to look for opportunities to amplify those messages, and greatly appreciate CDC’s 

support and willingness to speak regularly to the Medicaid and CHIP state staff.

On February 11, 2022, CMS issued an updated Medicaid COVID-19 Toolkit that addresses 

Medicaid policy for coverage and reimbursement of COVID-19 vaccines. That is available

on the Medicaid.gov website. On December 2, 2021, CMS announced that state Medicaid 

agencies are now required to cover vaccine counseling visits when a vaccine is not 

administered for most children enrolled in Medicaid up to age 21 under the Early and Periodic 

Screening, Diagnostic and Treatment (EPSDT) program. Because of this change, CMS will now 

consider certain COVID-19 vaccine counseling visits for children and youth to be COVID-19 

vaccine administration. For those visits, state expenditures can be federally matched at 100% 

during the coverage period under the ARP.

 

Food and Drug Administration 

Dr. Fink presented the FDA update, reporting that there were no new EUAs or vaccine 

approvals since ACIP last met. FDA continues its active and ongoing review of several

submissions for EUAs for COVID-19 vaccines, as well as reviews of BLA and supplemental BLA 

(sBLA) applications for various COVID and non-COVID vaccines. FDA expects to be able to 

provide updates on regulatory actions related to some of these ongoing reviews the next time

ACIP convenes. In the meantime, FDA also continues to be actively engaged with public health 

authorities and international regulatory authorities to work out considerations and policies to

address emerging data related to the COVID-19 pandemic, as well as the needs for further 

development and authorization of COVID-19 vaccines to address the pandemic.

Health Resources and Services Administration

Dr. Rubin presented the update for HRSA from the Division of Injury Compensation Programs. 

The National Vaccine Injury Compensation Program (VICP) continues to process an increased 

number of claims. In FY21, petitioners filed 2057 claims with the VICP. Nearly $208.3 million 

was awarded to petitioners. Approximately $36.5 million was awarded for attorneys’ fees and 

costs, which includes compensated and dismissed cases. In FY22, petitioners filed 327 claims 

with the VICP as of February 1, 2022. Nearly $82 million was awarded to petitioners, including 

attorneys’ fees and costs. As of February 22, 2022, the VICP had a backlog of 1462 claims 

alleging vaccine injury that are awaiting review. As of February 1, 2022, the Countermeasures 

Injury Compensation Program (CICP) has received 6540 claims alleging injuries and deaths 

from COVID-19 countermeasures have been filed. This included 3700 claims alleging injuries 

from COVID-19 vaccines. More information about the CICP can be found on the HRSA website. 

Indian Health Services

Dr. Clark presented the IHS update. Like other healthcare delivery systems, the IHS continues

to confront the challenges of the current pandemic and its impact on both routine and SARSCoV-2-specific immunization efforts. As it has done since September 2020, the IHS COVID-19 

Vaccine Task Force coordinates the distribution and administration of COVID-19 vaccines 

agency-wide, including at federal direct care facilities, tribal health programs, and urban Indian 

organizations that have elected to receive vaccines through the IHS jurisdiction. In collaboration 

with federal, tribal, and urban Indian organization partners, the IHS Vaccine Task Force efforts 

support an efficient system of distribution, prioritization, communication, administration,
ACIP Meeting Summary February 23-24, 2022 

46

data management, and safety monitoring for approved and authorized COVID vaccines across 

356 federal, tribal, and urban facilities. The IHS has prioritized equitable access to COVID 

vaccines throughout Indian country. As of February 21, 2022 within the IHS jurisdiction, over 2.7 

million COVID-19 vaccines were distributed and over 2.1 million vaccines were administered by 

participating federal, tribal, and urban facilities. According to current CDC tracking data, among 

the estimated 2.1 million people served at IHS facilities, 41% are fully vaccinated and 28%

of those fully vaccinated have received a booster dose. IHS will continue its efforts to maximize 

COVID vaccine coverage rates, especially among the most vulnerable members of the Tribal 

communities it serves. 

Across its 3 surveillance systems to date, IHS COVID vaccine safety monitoring has 

demonstrated a reassuring safety profile consistent with other national vaccine safety 

surveillance systems. The IHS routinely collaborates with the CDC and engages with Tribal 

leaders in support of vaccine confidence among the American Indian/Alaskan Native (AI/AN) 

service population. Routine tracking of IHS pediatric immunization coverage indicates the 

decline in vaccine coverage for children and adolescents, which has been amplified by the 

COVID-19 pandemic. Beginning in Spring 2021, the IHS initiated a pediatric immunization 

initiative called “Safeguard our Future: Protect Tomorrow, Vaccinate Today.”16 Communication 

strategies have included blog posts, a parent toolkit, and educational webinars to highlight the 

topic and to share best practices. Meanwhile, information technology tools and training sessions 

have helped users to identify and reach out to patients missing recommended vaccines. In 

addition, IHS facilities have been invited to participate in a quality improvement project targeting 

changes in immunization workflow to support improved and sustained pediatric vaccination 

coverage. During the 2021-2022 influenza season, the IHS immunization program continues to 

organize educational webinars, disseminate ACIP influenza vaccine recommendations, 

coordinate supply chain logistics, and distribute facility resources in support of the Influenza 

Immunization Action Plan. The IHS immunization program is planning to leverage COVID-19 

vaccination strategies for the efficient implementation in its service population of new and 

expanded adult pneumococcal, zoster, and HepB vaccine eligibility recommendations by the 

ACIP. 

National Institutes of Health 

Dr. Beigel from National Institute of Allergy and Infectious Disease (NIAID) presented the NIH 

update, reporting that the COVID-19 work over the last few months has been very interesting in 

terms of defining immune correlates of protection for COVID-19. NIAID researchers and 

collaborators found that levels of binding and neutralizing antibodies to the spike protein 

correlated with the degree of VE in the Phase III mRNA-1273 COVID-19 vaccine trial, which 

was published about a month ago. The results of the heterologous COVID-19 booster vaccine 

trial also were published. The antibody responses have been previously presented

to ACIP and formed the basis of heterologous booster vaccines. The publication provides

additional details, additional time points, and a description of T cell-mediated responses to the 

heterologous booster vaccines—a critical part of evaluating these vaccines. As part of that trial, 

neutralizing antibodies to the Omicron variant were assessed and it was found that most 

homologous and heterologous combinations increased humoral immunity to Omicron. Additional 

work has been done to improve COVID-19 vaccine immunogenicity in immunocompromised 

populations. A new trial has begun to assess the antibody response to additional doses of an 

mRNA vaccine in kidney and liver transplant recipients. This study is unique because it is 

16 https://www.ihs.gov/sites/newsroom/themes/responsive2017/display_objects/documents/SafeguardOurFutureVaccine 

ToolkitforParentsandFamilies.pdf 
ACIP Meeting Summary February 23-24, 2022 

47

testing whether an additional dose of mRNA alone or with concurrent reduction of 

immunosuppressive medication will improve antibody response. An NIH-funded study found that 

vaccinating women against SARS-CoV-2 in mid- to late-pregnancy could provide infants with 

some degree of protection against COVID-19 through 6 months of age. There continues to be 

work on pandemic preparedness, including a workshop on pandemic preparedness in

November 2021. The NIAID Pandemic Preparedness Plan17 was issued in December 2021 for 

future public health emergencies caused by infectious diseases. There also continues to be 

work toward universal coronavirus vaccines. Details of these and several additional updates 

were provided in a written summary.

Office of Infectious Disease and HIV/AIDS Policy 

Dr. Kim presented the OIDP update on behalf of the National Vaccine Program Office (NVPO), 

OIDP, and the Office of the Assistant Secretary for Health (OASH). Along with contributors from 

a number of federal agencies, OIDP prepared a draft Vaccine Schedule Implementation Plan as 

a companion document to the National Strategic Plan for the United States | 2021–202518

released in 2021. The implementation plan outlines federal actions in support of national 

vaccination goals. Soon there will be a Federal Register Notice (FRN) for a 30-day public 

comment period, for which Dr. Kim invited feedback. Work is underway to strengthen the case

with transitioning 3 developmental objectives and immunizations to core objectives in Healthy 

People 2030. These developmental objectives are to: 1) increase the proportion of women who 

get the Tdap vaccine during pregnancy; 2) increase the proportion of information systems that 

track immunizations across the lifespan; and 3) increase the proportion of adults aged ≥19 

years who get recommended vaccines. OIDP particularly welcomes information exchange from 

its partners who work on composite adult vaccination data. With the new ACIP universal HepB 

vaccine recommendation for adults aged 19-59 years that is pending publication in the MMWR, 

OIDP is working with CDC and other partners that are interested in promoting HepB vaccination 

in routine preventive adult care and will be assisting with promotional activities. The National 

Vaccine Advisory Committee (NVAC) turned 35 this year. The February 11-12, 2022 NVAC 

meeting covered several timely topics on vaccines, including prohibiting discrimination in 

COVID-19 vaccination programs, COVID-19 VE, expanding Immunization Information Systems 

(IISs), and vaccine safety. The next NVAC meeting will be June 15-16, 2022.

PNEUMOCOCCAL VACCINES

Session Introduction

Dr. Katherine Poehling (ACIP WG Chair) introduced the pneumococcal vaccines session, 

beginning with a review of current pneumococcal recommendations in children. PCV13 is 

routinely recommended as a 4-dose series at 2, 4, 6, and 12-15 months—sometimes known as 

a 3+1 schedule. PCV13 catch-up options are for healthy children through 59 months of age and 

children with underlying conditions through 71 months. In terms of PCV13 and PPSV23 for 

children 24-71 months of age with underlying conditions, the recommendation is to complete the 

PCV13 series followed by PPSV23 ≥8 weeks after the last PCV13. Children who are

immunocompromised or with sickle cell disease or asplenia can receive a second dose of 

PPSV23, which is recommended 5 years after the first dose of PPSV23. To put this into context,

this table shows the underlying conditions in immunocompetent, functional or anatomic 

asplenia, and immunocompromised risk groups:

17 https://www.niaid.nih.gov/sites/default/files/pandemic-preparedness-plan.pdf 18 https://www.hhs.gov/sites/default/files/HHS-Vaccines-Report.pdf 
ACIP Meeting Summary February 23-24, 2022 

48

PCV13 and/or PPSV23 is recommended for children 6-18 years of age with underlying 

conditions. For these children, 1 dose of PPSV23 is recommended for children with chronic 

heart/lung disease, or diabetes. If never received, 1 dose of PCV13 is recommended followed 

by PPSV23 ≥8 weeks for children with immunocompromising conditions, cerebrospinal fluid

(CSF) leak, or cochlear implants. For children with immunocompromising conditions,

a second dose of PPSV23 is recommended ≥5 years after the first PPSV23 dose. The following 

table illustrates recommendations for children aged 6-18 years with underlying medical 

conditions: 
ACIP Meeting Summary February 23-24, 2022 

49

The reason the Pneumococcal Vaccine WG is working on this now is due to anticipated PCV15 

licensure in the first quarter of 2022 and anticipated PCV20 licensure in the second quarter of 

2023. Given this, the policy questions proposed by the WG are:

 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 with underlying medical conditions 2-18 

years of age as an option for pneumococcal conjugate vaccination according to currently 

recommended dosing and schedules?

It is important to note that the WG is not currently considering any change in the recommended 

pneumococcal vaccine dosing or schedule. This session included presentations on the 

epidemiology of pneumococcal disease and pneumococcal vaccine coverage in US children; 

PCV15 Phase 3 study results in children; GRADE and EtR for PCV15 use in US children; and a 

summary of next steps. 

Epidemiology of Pneumococcal Disease and Pneumococcal Vaccine Coverage in US 

Children

Mr. Ryan Gierke (CDC/NCIRD) began with a brief background on the spectrum of 

pneumococcal disease. Pneumococcus is transmitted through airborne droplets from person-toperson. It can be colonized or carried in the nasopharynx and then spread locally to the ears to 

cause otitis media or sinusitis. It also can be aspirated and cause pneumonia. Pneumococcus 

can also infect the blood and cause septicemia. These different infections can be characterized 

into noninvasive and invasive disease. Invasive pneumococcal disease (IPD) is a less frequent, 

less severe form of illness. Noninvasive disease is more frequent. In children, otitis media is one 

of the most common forms of pneumococcal disease.

Mr. Gierke then reviewed current pneumococcal vaccine coverage in children, recent IPD data 

assessing the impact of PCV13 on IPD burden and serotype distribution, IPD burden caused by 

serotypes covered in the new conjugate vaccines (PCV15 and PCV20), what is known to date 

regarding the impact of PCV13 on all-cause pneumococcal pneumonia among children, recent 

estimates of pneumococcal pneumonia incidence, the impact of PCV13 incidence estimates 

and serotype distribution among acute otitis media (AOM), and serotype distribution of 

pneumococcal carriage among children.

As a reminder of the current pneumococcal vaccines in use and the serotypes covered by each, 

PCV13 pneumococcal conjugate vaccine covers 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 

18C, 19A, 19F, 23F) and is routinely recommended for all children aged less than 2 years. A 

dose is given at 2, 4, and 6 months of age with an additional dose at between 12-15 months of 

age. A catch-up option is recommended through age 4 in healthy children or age 5 among 

children with certain medical conditions. PCV13 also is recommended for children aged 6-18 

years with certain medical conditions. Additionally, PPSV23 polysaccharide vaccine has 23 

serotypes (the 13 from PCV13 plus 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, 33F) and is 

recommended for children aged 2 years and older with certain medical conditions. Coverage of 

pneumococcal conjugate vaccine among children has remained consistent in recent years, with 

over 90% of children receiving 3 doses and over 80% receiving 4 doses by 24 months of age. 
ACIP Meeting Summary February 23-24, 2022 

50

No declines were observed in birth years 2017-2018 compared to 2015-2016.19 Although data 

for birth year 2018 are considered preliminary, CDC will continue to monitor this.

In terms of the impact of PCV13 on pediatric IPD incidence and serotype distribution, data on 

IPD are obtained from the Active Bacterial Core surveillance (ABCs). ABCs provides populationbased surveillance at 10 sites across the US. Cases are defined as “pneumococcus isolated

from a normally sterile site.” Isolates are serotyped at reference laboratories using whole 

genome sequencing, Quellung, or PCR. For this analysis, serotypes were grouped by vaccinetype and serotype 6C was grouped with PCV13 types due to the cross-protection provided by 

the 6A antigen. Regarding IPD incidence rates in children and adult age groups, incidence is 

highest among older adults and also is high among children under 5 years of age. Incidence is 

low for children aged 5-17 years, with approximately 25% of cases in this age group having a 

medical condition that is an indication for PCV13.

Looking at the incidence rates of IPD among children under 5 years of age from 2007-2019,20

rates of PCV13-type IPD in children declined sharply after the introduction of PCV13 in 2010. 

Comparing 2007-2008 rates to the 2018-2019 rates, there was an almost 90% reduction in 

PCV13-type IPD. This resulted in a 67% reduction in overall IPD over the same time period. 

However, declines and PCV13-type IPD rates plateaued after 2013 at around less than 2 cases 

per 100,000. This trend continued on through 2019. Rates of non-PCV13 serotypes remained 

relatively stable over this time period. No replacement disease has been observed by nonvaccine serotypes in children at this time. Examining IPD rates for individual serotypes and 

PCV13 plus 6C among children less than 5 years of age from 2011-2019, rates of IPD declined

for many PCV13 serotypes after PCV13 introduction in children. However, reductions were not 

seen in serotypes 3 or 19F. Together, these 2 serotypes accounted for almost 80% of the 

remaining PCV13-type disease in 2018-2019. Serotype 9A has declined substantially, but still 

accounts for about 14% of remaining disease. For older children aged 5-18 years, serotypes 3 

and 19F make up most of the remaining PCV13-type disease in this age group, accounting for 

around 65% of remaining disease. Rates of 19A still accounted for 21% of remaining disease in 

2018-2019.

To review the current pediatric IPD burden among PCV15 and PCV20 serotypes, the serotypes 

covered by new conjugate vaccine PCV15 include those in PCV13 plus 22F and 33F. PCV20 

includes the serotypes in PCV13 and PCV15 plus serotypes 8, 10A, 11A, 12F, and 15B. For 

analysis purposes, PCV15 non-PCV13 included serotypes 22F and 33F; PCV20 non-PCV15 

included serotypes 8, 10A, 11A, 12F, and 15B; and PPSV23 non-PCV20 included serotypes 2, 

9N, 17F, and 20. Looking at incidence of IPD among children less than 5 years of age grouped 

by conjugate vaccine-type from 2011-2019, PCV13-type IPD decreased after PCV13 

introduction in children. In 2018-2019, incidence was about 1.5 cases per 100,000 population. 

PCV15 non-PCV13 serotypes and PCV20 non-PCV15 serotypes have remained relatively 

stable. In 2018-2019, incidence due to these serotypes was 1.2 and 1.6 cases per 100,000 

respectively. For children aged 5-18 years, incidence of PCV13-type IPD also decreased since 

PCV13 introduction in younger children. However, there was more variability in the older ages 

that is likely due to the smaller rate of disease. In 2018-2019, PCV13-type IPD incidence was 

0.5 per 100,000 population . PCV15 non-PCV13 serotypes and PCV20 non-PCV15 serotypes 

have remained relatively stable. In 2018-2019, incidence due to these serotypes was 0.2 and 

0.3 per 100,000 population respectively. From 2018-2019, PCV13 serotypes still account for 

around 20% to 35% of IPD in children. PCV15 non-PCV13-type disease accounted for an 

19 https://www.cdc.gov/mmwr/volumes/70/wr/mm7041a1.htm 20 Active Bacterial Core Surveillance (ABCs) Report Emerging Infections Program Network Streptococcus pneumoniae, 2019. 

Available: SPN_Surveillance_Report_2019.pdf (cdc.gov) 
ACIP Meeting Summary February 23-24, 2022 

51

additional 16% to 17% of IPD. PCV20 non-PCV15 type disease accounted for 13% to 15% of 

IPD, while PPSV23 non-PCV20 accounted for 1 to 5% of IPD. Nonvaccine-types accounted for 

32% to 46% of disease in children.

To review data on the impact of PCV13 on all-cause and pneumococcal pneumonia and 

estimated incidence of pneumonia in children, Mr. Gierke first reviewed the findings from recent 

studies examining the impact of PCV13 on pneumonia in children. An analysis of US insurance 

claims data comparing years 2008-2009 versus 2014 found a 17% to 35% reduction in rates

of all-cause pneumonia among children depending on age group, with the largest reductions 

among children less than 2 years of age.21 A study analyzing US healthcare claims data for 

2007-2009 compared to 2011-2012 found a reduction of 17% to 21% in all-cause inpatient 

pneumonia depending on age group. However, no reductions were observed in older children 

aged 5-17 years. The same study assessed changes in pneumococcal pneumonia, finding 40% 

and 51% reductions among ages <1 and 5-17 years respectively. However, there were no 

significant reductions among children aged 2-4 years.22

Estimates of pneumonia among children can have a wide range for several reasons, including 

the data sources used, the time period examined, the definition of pneumonia used, and the age 

of the populations. A recent publication of 2014 US insurance claims data estimated the rate of 

all-cause pneumonia among children to be around 1300 to almost 4000 episodes per 100,000 

person years, depending on the age group.23 The lowest rates were among children aged 5-17. 

Based on recent national inpatient sample data,24 estimates of inpatient pneumonia among 

children ranged from around 87 to 680 cases per 100,000 population based on age group, with 

the lowest rates among children 5-17 and higher rates among the younger ages. Studies 

examining pneumococcal pneumonia incidence among hospitalized children under 5 years of 

age using data from years 2011-2012 found a range of 6-18 cases per 100,000 population.

A recent study examining the impact of PCV13 on AOM in children that analyzed US insurance 

claims data from years 2008-2014 found a 14% reduction in AOM among children ≤1 year of 

age. Older age groups did not have significant reductions in AOM over the same time period.25

Estimates of AOM-like pneumonia can have a wide range for several reasons (e.g., data 

sources used, time period, definition used, and age of population). A recent publication of 2014 

US insurance claims data estimated the incidence of AOM among children <5 years of age to 

be approximately 30,000 to almost 50,000 episodes per 100,000 person years, depending on 

age group.26 In a prospective cohort study of children at Rochester, New York, Streptococcus 

pneumoniae (S. pneumoniae) was isolated from 24% of children aged 6-36 months with 

clinically diagnosed AOM.27 The same study from Rochester reported serotype distribution 

among children with pneumococcal AOM from 2015-2019. Based on specimens collected by 

either nasopharyngeal swab (NP) or middle ear fluid sample by tympanocentesis, serotype 

distribution among AOM cases were similar, with PCV15 non-PCV13 serotypes accounting for 

between 6% to 8% of AOM in this population.28

21 Tong BMC 2018 

22 Simonsen Lancet 2014 

23 Simonsen et. al. lowest, Jain et. al. highest 

24 National Inpatient Sample, 2018-2019

25 Tong et al, BMC 2018 

26 Adapted from Tong BCM 2018 

27 Kaur EJCMID 2022 

28 Adapted from Kaur BCM 2022 
ACIP Meeting Summary February 23-24, 2022 

52

Comparing the serotype distribution of pneumococcal AOM cases found in the Rochester area 

to the serotype distribution among IPD cases in the New York State ABC surveillance area, 

which includes Rochester, a greater proportion of non-vaccine serotypes were observed to be 

causing AOM compared to IPD. PCV15 non-PCV13 serotypes contribute to around 6% to 8%

of AOM compared to 18% of IPD in the New York ABC surveillance area.29 The Rochester 

prospective study of children with AOM also examined NP carriage of pneumococcus among 

healthy children in 2015-2019. Children in the Rochester area aged 6-9 months were enrolled 

and followed through 36 months of age having NP swabs taken during routine well-child visits. 

Serotype distribution for pneumococcal carriage in the New York study and additional 

unpublished carriage data was available courtesy of a study conducted by the Georgia 

Emerging Infections Program (EIP).30 The EIP study was among children aged 6-59 months 

presenting to a children’s hospital emergency department (ED) in the Atlanta area for any 

reason. Consenting children had an NP swab taken at the time of visit. The serotype distribution 

of pneumococcal carriage in children was similar in these 2 distinct geographic areas. In both 

study populations, there was a greater proportion of non-vaccine serotypes compared to 

serotypes causing AOM and IPD. PCV15 non-PCV13 serotypes contributed to 3% to 4% 

pneumococcal carriage in children in these populations compared to around 6% to 8% of AOM 

and 16% to 17% of IPD.

In conclusion, overall IPD and PCV13-type IPD incidence has plateaued among children <5 

years of age since 2013-2014. Incidence of IPD caused by PCV15 serotypes also has remained 

stable. In older children 5-18 years of age, overall IPD rates are small and even a few cases can 

impact trends. Among cases in this age group, 25% had a medical condition

that was indicated for PCV13. After pediatric PCV13 introduction, all-cause and pneumococcal 

pneumonia showed modest declines among children and the impact varied by age group. 

Burden estimates of all-cause and pneumococcal pneumonia varied across studies. Serotype 

distribution among pneumococcal pneumonia is unknown in children. AOM after pediatric 

PCV13 introduction saw modest declines among children, with less impact among older 

children. The burden of AOM in children remains high, with pneumococcus contributing to a 

quarter of clinically-diagnosed disease. AOM and IPD data show that 2 additional serotypes 

included in PCV15 cause 8% to 17% of remaining pneumococcal disease in children <5 years 

of age.

Discussion Summary

Dr. Hahn (CSTE) noted that the definitions for “noninvasive” versus “invasive disease” were 

somewhat counterintuitive. COVID-19 and other respiratory diseases are usually defined by 

severity. Therefore, it would be worth a more in-depth discussion about why pneumonia would 

not be considered invasive disease.

Mr. Gierke explained that colonization of the nasopharynx generally precedes disease. That can 

lead to aspiration, which can cause pneumonia. Pneumonia can be invasive or noninvasive, 

because after causing pneumonia, it also can go on to cause septicemia. For the purpose of this 

analysis, invasive and noninvasive pneumonia were grouped together. However, there is a 

much higher proportion of noninvasive pneumonia than invasive.

Dr. Daley asked what serotypes were responsible for the largest proportion of AOM in the 85% 

not caused by identified serotypes in the Rochester study.

29 Adapted from Kaur BCM 2022; IPD from ABCs 2015–2019 

30 Adapted from Kaur BCM 2022; Data curtesy of GA EIP, unpublished
ACIP Meeting Summary February 23-24, 2022 

53

Mr. Gierke indicated that based on that study, an uptick was noticed in 35B, 15B/C, and 23B

after PCV13 introduction. For children <5 years of age, 15C is one of the top non-vaccine-types. 

If grouped together 15B and 15C would be the top serotypes. In addition, 23B is also seen in a 

lot of AOM cases, and 23B and 35B are both ranking as the highest non-vaccine types among 

children for both IPD and AOM.

PCV15 Phase 2/3 Study Results in Children

Dr. Natalie Banniettis (Merck Research Laboratories, Merck & Co.) presented a high-level 

clinical overview of pneumococcal polysaccharide 15-valent conjugate vaccine (V114, 

VAXNEUVANCE) that included an overview of the rationale for development of V114, the 

Phase 3 pediatric clinical development program, immunogenicity results, safety results, 

supportive studies, and brief conclusions from the supportive studies and the integrated analysis

of preterm infants. Since the advent of PCVs, the incidence of IPD among children has 

decreased considerably, mainly due to reductions in vaccine-type disease.31 However, serotype 

3, which is included in PCV13, persists and is one of the top serotypes causing IPD in US

children <5 years of age in the post-PCV era.32 One can also appreciate the relative increase of 

non-vaccine types, such as 22F and 33F included among the leading serotypes causing IPD. As 

such, new PCVs targeting additional serotypes have the potential to further reduce IPD burden 

among children.

V114 was developed to expand vaccine coverage to 2 serotypes not targeted by currently

licensed pediatric PCVs, 22F and 33F, while maintaining or improving upon immune responses 

to current vaccine serotypes shared with PCV13 to help sustain the progress achieved to date

and ensure the safety profiles comparable to licensed PCVs. In 2019, Breakthrough Therapy 

Designation was granted by the US FDA for the V114 pediatric indication, with priority review by 

both US FDA and Health Canada underscoring the public health value of V114. Importantly, the 

availability of V114 would introduce a second supplier to the US market, which will increase the 

availability of PCVs for the US population and globally. Of note, V114 was licensed in adults in 

July 2021. The anticipated date for the pediatric submission is April 1, 2022. 

The V114 pediatric clinical 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 through 17 years of age. The Phase 3 program includes 9 Phase-3 studies comprised

of approximately 8500 participants of whom about 5300 received V114. These 9 Phase-3 

studies include 3 pivotal studies in infants evaluating 3+1 dosing in protocol V114-029 and 2+1 

dosing in protocols V114-025 and V114-026, the latter of which is still ongoing. There are 3 

supportive studies evaluating PCV in infants and catch-up vaccinations through 17 years

of age, as well as a large safety study in infants. There are 3 studies in special populations at 

increased risk for IPV, including children with sickle cell disease, children who live with HIV, and 

hematopoietic stem cell transplant (HSCT) recipients—a study that is ongoing. Another ongoing

study in the program is protocol V114-032, the AOM efficacy study.

Safety and tolerability evaluation in the program was based on solicited, non-solicited, and 

SAEs. Immunogenicity was evaluated using validated pneumococcal electrochemiluminescence

(ECL) and multiplex opsonophagocytic activity (OPA) assays. The ECL was bridged to the 

WHO reference enzyme-linked immunosorbent assay (ELISA). Evaluation was based on 

31 US CDC ABC Surveillance Network, 1998-2017 

32 Epidemiology of IPD following 18 years of PCV use in the US; Pilishvili et al, CDC
ACIP Meeting Summary February 23-24, 2022 

54

serotype-specific antibody responses including IgG response rate ≥0.35 μg/mL, IgG GMC, and

serotype-specific OPA GMTs. In infants, immunogenicity was measured 30 days post-primary 

series immediately prior to the toddler dose and 30 days following the toddler dose. In children 

aged 2 years and up, immunogenicity was assessed immediately before and 30 days following 

vaccination with a single dose of PCV. Of note, the higher burden of disease in infants

under 1 year of age in comparison to older children underscores the need for strong vaccineinduced immune responses in this age group. As such, the demonstration of non-inferior 

immune responses to the standard of care licensed vaccine after the infant series

at post-does 3 is a regulatory requirement for the pediatric indication when licensing new PCVs 

in the US.

Transitioning now to the features of Phase 3 Pivotal Study Protocol V114-029. Protocol 029 was 

designed to evaluate the safety and immunogenicity of V114 PCV schedule administered at 2, 

4, 6, and 12-15 months of age (3+1 dosing regimen) among 1720 healthy infant participants

who were randomly assigned in a 1:1 ratio to receive V114 or PCV13. The study also evaluated 

the co-administration with licensed pediatric vaccines. Vaccination report cards were reviewed 

at study visits and via telephone contacts at Day 15 after each vaccination, and at 6 months 

after the last PCV dose. The primary safety objective was the evaluation of safety and 

tolerability of V114 with respect to AEs. The primary immunogenicity objectives were the noninferiority evaluation of IgG response rates and GMC ratios. The secondary immunogenicity 

objectives included a descriptive evaluation of OPA GMT and non-inferiority evaluation of 

antigen-specific response rates to the co-administered vaccines. Additionally, a superiority 

evaluation was conducted for responses to the unique serotypes 22F and 33F and the shared 

serotype 3. 

In regard to the primary objective of IgG response rates after the third dose, a conclusion of 

non-inferiority of V114 to PCV13 was based on the difference in the proportion of responders 

between the arms being less than 10 percentage points. V114 met non-inferiority for all 13 

shared serotypes. As per regulatory requirements, responses for the unique serotypes in the 

V114 group were compared with the lowest observed response rate in the PCV13 group, 

excluding serotype 3. Serotype 23F was 92%, so V114 met non-inferiority for the 2 unique 

serotypes. In regard to the primary objective of IgG GMC post-dose 3, a conclusion of noninferiority of V114 to PCV13 was based on the lower bound of the 95% confidence interval for 

the GMC ratio being greater than 0.5. V114 met non-inferiority for 12 out of the 13 shared 

serotypes, narrowly missing the pre-defined criterion for serotype 6A with a 95% confidence 

interval lower bounds of 0.48. For the unique serotypes, for regulatory requirements IgG GMCs 

for the V114 groups were compared with the lowest observed IgG GMC in the PCV13 group 

excluding serotype 3, which in this case was serotype 4 at 1.4 μg/mL, so V114 met noninferiority in this case as well. In terms of the toddler dose, V114 met non-inferiority criteria for 

all 13 shared serotypes based on IgG GMC at post-dose 4 with all lower bounds greater than 

0.5. Similarly for the unique serotypes, V114 met non-inferiority based on IgG GMC at postdose 4. 

Transitioning from the primary non-inferiority objectives to the secondary superiority objectives 

starting with the post-dose 3 response rates for the unique serotypes, a conclusion of superiority 

of V114 to PCV13 was based on the difference in the proportion of responders between the 

arms being greater than 10 percentage points. Comparing responses of V114 directly to 

responses of PCV13, V114 met superiority criteria for both unique serotypes. For IgG GMC for 

the unique serotypes, a conclusion of superiority was based on the lower bound of the GMC 

ratio being >2 or at least double. V114 met superiority criteria at both post-dose 3 and post-dose 

4. Regarding the shared serotype 3 and response rates at post-dose 3, the superiority criterion 
ACIP Meeting Summary February 23-24, 2022 

55

was based on the difference in response rates being greater than zero. With a lower bound of 

12.1, V114 met the superiority criterion for serotype 3. When looking at serotype 3’s IgG GMCs 

for post-dose 3 and post-dose 4 time points, superiority was based on the lower bound of the 

ratio being greater than 1.2. V114 met superiority here as well.

In terms of co-administered vaccines, all lower bounds met non-inferiority criteria. Additionally, 

for the IgG GMC to pertussis, V114 met non-inferiority with lower bounds of the ratios being 

greater than 0.67 for each evaluated pertussis antigen. When considering each of the 15 

serotypes in V114 and all the concomitant antigens assessed, V114 met 73 out of 74 individual 

immunogenicity hypotheses in Protocol 029. Furthermore, a descriptive evaluation of functional 

activity at post-dose 3 and post-dose 4 demonstrated generally comparable OPA GMTs

for the shared serotypes and higher GMTs for the unique serotypes in V114 recipients as 

compared with PCV13. 

The pediatric V114 program was designed to generate a robust safety database to characterize 

the safety profile of V114 in the pediatric population. This presentation focused on the 7 studies 

included in the initial US filing with one Phase-2 and 6 Phase-3 studies. These 7 studies

encompass approximately 7200 children aged 6 weeks to 17 years, of whom approximately 

4800 received V114. About 6100 were infants enrolled at 6-12 weeks of age, of whom about 

4300 receive V114. Older children through 17 years of age receiving a single dose

of PCV were enrolled in 3 studies.

Regarding the integrated Phase 3 safety results pooled across Protocol 31, the safety study, 

Protocol 029, 2 pivotal studies, and Protocol 027, the interchangeability study, the baseline 

characteristics and demographics of participants included in the integrated safety analysis are 

comparable between the groups. Notably, the population was diverse with regard to race and 

ethnicity. In terms of the integrated safety summary with about 3000 in the V114 group and 

nearly 1500 in the PCV13 group, V114’s safety profile was generally comparable to that of

PCV13. The proportion of participants with AEs (e.g., injection sites, systemic and vaccinerelated AEs, and SAEs) were generally comparable between the groups. Solicited events 

accounted for the majority of all AEs and vaccine-related AEs in both groups. In both groups, 

the majority of AEs were mild or moderate in intensity with a duration of 3 days or less. There 

were no discontinuations due to vaccine-related AEs in the integrated analysis. Vaccine-related 

SAEs of pyrexia were reported for 2 participants in the V114 group. The events were considered 

mild and moderate in intensity, and both resolved in 3 days. A total of 4 deaths were reported, 2 

in each group and none of which were deemed to be vaccine-related by the investigators. The 

distribution of maximum body temperatures for the integrated analysis also was generally 

comparable between intervention groups, with the majority being afebrile 7 days postvaccination. Of those with temperatures greater ≥104.40F, the majority were less than 101.30F 

in both groups.

To briefly summarize the key conclusions for the supportive studies that were evaluated 

descriptively, Protocol 027 is a study of interchangeability, otherwise known as switch or mixed 

dosing, when the series is initiated with PCV13. Protocol 024 is a study of catch-up vaccination

through 17 years of age, with age-appropriate regimens of 3, 2, or a single dose of PCV.

Protocol 023 is a study in children with sickle cell disease aged 5-17 years receiving a single 

dose of PCV. Protocol 030 is a study in children living with HIV aged 6-17 years receiving a 

single dose of PCV followed sequentially by PPSV23. Infants born prior to 37 weeks gestational 

age were integrated for descriptive analysis. The integrated preterm population presented are

comprised of approximately 290 preterm infants. The youngest gestational age enrolled
ACIP Meeting Summary February 23-24, 2022 

56

in the V114 group was 27 weeks and the distribution of gestational ages between groups was 

comparable, with a median gestational age of approximately 36 weeks.

The overall safety conclusions from the supportive studies and the integrated preterm infant 

analysis were that V114 is well-tolerated and safe in these populations. The overall

immunogenicity conclusions were that V114 is immunogenic to all 15 serotypes, both 

quantitatively and qualitatively, with comparable responses for the shared serotypes and higher 

responses for the 2 unique serotypes as compared with PCV13. The key conclusions of the 

V114 pediatric clinical program are that in children with an unmet medical need in 

pneumococcal disease prevention, V114 is well-tolerated, with a safety profile that is consistent 

with licensed PCV. V114 induces robust immune responses to the 13 serotypes shared with 

PCV13 without significant loss of immunogenicity. V114 is superior to PCV13 for the shared 

serotype 3 and the unique serotypes 22F and 33F, which are of high public health importance. 

Therefore, V114 has the potential to significantly address the burden of remaining 

pneumococcal disease due to vaccine-types and leading non-vaccine-types in children.

Discussion Summary

Dr. Haupt, Head of Vaccines and Infectious Diseases and Medical Affairs for Merck, thanked 

the ACIP Pneumococcal Vaccines WG for all of the efforts that were undertaken to ensure a 

comprehensive review of all the evidence supporting the recommendation for PCV15 in 

children. Additionally, Merck recognizes that there have been major efforts by the ACIP and 

CDC to consider the PCV15 pediatric conditions so quickly following all of the work that was just 

done and is still ongoing for the adult pneumococcal vaccine recommendations. That all has 

been done in the context of the additional work related to the COVID-19 pandemic. Based on 

timeline presented during this session and assuming licensure, a vote for the PCV15 vaccine in 

children could occur during the June 2022 ACIP meeting. As noted, Merck submitted the data 

file to the FDA in the third quarter of 2021. The FDA granted Merck a priority review and 

established a date of April 1, 2022. Therefore, Merck expects licensure by April 2022. That is 

important as the critical criterion for priority review is that a medicine or vaccine addresses an 

unmet medical need. Including serotypes 22 and 33F in the PCV15 vaccine that are not 

included in PCV13 offers opportunity to address diseases caused by these serotypes and with a 

superior immunological response in serotype 3, may provide some protection against serotype 3 

as well. Merck will continue to support the WG as they review all the data that are needed to 

inform the vote that is upcoming.

Referring to Slide 20, Dr. Poehling requested additional information about the interpretation of 

the differences between the post-dose 3 and post-dose 4 responses.

Dr. Banniettis responded that the interpretation was that there was no significant difference

after the third dose with Haemophilus influenzae (Hib), but V114 met non-inferiority for Hib-PRP 

at post-dose 4. Thus, the responses were comparable between the 2 arms. The plot shows the 

ratio between V114 and PCV13.

Dr. Fink further explained from a regulatory approach to this non-inferiority testing. There are 

statistical criteria for non-inferiority testing and then each statistical criterion is associated with a 

clinical understanding or assessment. In a non-inferiority analysis, what FDA would consider to 

be a clinically meaningful non-inferiority finding could, in a separate statistical analysis, be a 

statistically significant difference that FDA does not find to be clinically meaningful. FDA 

considers meeting the non-prespecified non-inferiority criterion to be clinically meaningful and 

would not consider what might be said to be a statistically significant difference. With the caveat 
ACIP Meeting Summary February 23-24, 2022 

57

of multiplicity control, FDA would not consider the apparent statistically significant difference to 

be clinically meaningful from a regulatory perspective.

Regarding Slide 25, Dr. Poehling requested additional clarification about the 2 pyrexia SAEs 

and the 4 deaths that were not considered to be vaccine-related.

Dr. Banniettis clarified that the 2 pyrexia events for the first the onset occurred the same day as 

Dose 1. Maximum body temperature was reported as 100.40F and concomitant vaccines 

included rotavirus vaccines, Hib, and combination vaccines with DTaP, IPV, and HepB. The 

second serious events of fever in the V114 group had onset on the same day as Dose 3. 

Maximum body temperature was reported as 102.90F. Concomitant vaccines were OPV and a 

combination vaccine with DTaP, Hib, and HebB. Among the 4 deaths that were deemed 

unrelated, 2 deaths occurred in the V114 group, 1 occurred on Day 2 relative to Dose 3 due

to congenital heart disease, and 1 death occurred on day 110 relative to Dose 4 due to cranial 

cerebral injury after a car accident. Of the 2 deaths in the PCV13 group, the first was on Day 25 

relative to Dose 1 from cardio-respiratory arrest due to sudden unexplained infant death, and 

the second death occurred on day 185 relative to Dose 2 from complications of head injury and 

septic shock.

Dr. Daley asked what caused the fevers to be designated as vaccine-related SAEs and whether 

a fever of 1050F was reported among vaccine recipients and V114.

Dr. Banniettis indicated that the SAE designation was based on specific criteria, one of which is 

hospitalization. The 2 pyrexia events were admitted to the hospital and therefore they 

constituted SAEs. Regarding the temperatures, the proportion of participants reporting a 

maximum body temperature greater than 1040F were low in both groups. Temperatures greater 

than or equal to 105.80F were reported in 0.2% in each intervention group.

Dr. Lee commented that fever distribution for Doses 1, 2, and 3 looked fairly comparable. 

However, the height of the fever for Dose 4 seemed somewhat different in the V114 group 

compared to PCV13. That time period tends to be the height of background rates for febrile 

seizures, which has been observed before with concomitant PCV13 and influenza vaccines. 

With that in mind, she wondered whether those with a temperature greater than 1040F seemed 

qualitatively different, whether there have been any associated febrile seizures, and whether 

any of these children received concomitant influenza vaccine.

Dr. Banniettis responded that apart from post-Dose 4 fevers greater than 105.80F, the 

temperature distribution was relatively comparable between the groups. It is important to 

remember what the concomitant vaccinations that are given with Dose 4 included MMR

and varicella vaccines. In regard to the difference between the arms, it just a difference of 0.2% 

and there is not anything specific to explain that in this particular situation. It also is important to 

point out that the sample size for V114 was approximately 2800 and the sample size for PCV13 

was around 1300, which may explain the discrepancy. The rate of febrile convulsions in the 

pediatric program was 0.3% in the V114 arm and 0.2% in the PCV13 arm. These particular 

events were not associated with febrile seizures. Influenza vaccine was not administered 

concomitantly during the pediatric program. 
ACIP Meeting Summary February 23-24, 2022 

58

GRADE and EtR for PCV15 Use in US Children

Ms. Jennifer Farrar (CDC/NCIRD) presented the WG’s interpretation on the use of 15-valent 

pneumococcal conjugate vaccine in children using the EtR Framework. After discussion with the 

Pneumococcal Vaccine WG, 2 PICO questions were decided for PCV recommendations:

 Should PCV15 be recommended as an option for pneumococcal conjugate vaccination 

according to currently recommended dosing and schedules for US children younger than 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 aged 2-18 years 

with underlying medical conditions?

Both policy questions compare PCV15 to the current vaccine recommendations and review the 

outcomes of vaccine-type IPD ,vaccine-type pneumonia, vaccine-type AOM, deaths due to 

vaccine-type pneumococcal disease, and SAEs following immunization. As a reminder, the EtR 

Framework consists of 7 domains: Public Health Problem, Benefits and Harms, Values, 

Acceptability, Feasibility, Resource Use, and Equity. This presentation focused on the domains 

Public Health Problem, Benefits and Harms, Values, and Equity. Available evidence is usually 

assessed for each policy question. However, given the overlap in available evidence for the 2 

questions being considered, the WG reviewed the 2 questions in parallel for each EtR domain.

Regarding whether pneumococcal disease is of public health importance in children, AOM is 

one of the most common reasons for outpatient care in children33,34 and S. pneumoniae is one

of the most common bacterial causes of AOM. However, administrative data have shown AOM

and pneumonia rates in children have decreased over time. IPD rates decreased after PCV 

introduction in children, but young children are at increased risk of pneumococcal disease. 

Among children less than 5 years of age, overall PCV13-type IPD incidence has plateaued 

since 2013-2014. The incidence of IPD caused by the unique PCV15 serotypes also has 

remained stable during this time. The 2 additional PCV serotypes caused 17% of IPD in 2018-

2019. Overall IPD rates in children aged ≥5 years have remained small and 25% of IPD in 

children aged 6-18 years was in children with immunocompromising conditions. The WG 

determined that pneumococcal disease is of public health importance in children.

For the benefits and harms domain, the WG reviewed each policy question and covered several 

questions:

 How substantial are the desirable anticipated effects for vaccine-type IPD, vaccine-type 

nonbacteremic pneumococcal pneumonia, vaccine-type acute otitis media, and deaths from 

vaccine-type disease.

 How substantial is the undesirable anticipated effect for SAEs?

 Do the desirable effects outweigh the undesirable effects?

 What is the overall certainty of this evidence for the critical outcomes in terms of 

effectiveness and safety of the intervention?

The search strategy included reviewing evidence for PCV15 from clinicaltrials.gov, PubMed, 

and additional resources provided by vaccine manufacturers and subject matter experts 

(SMEs). An initial 71 studies were identified. After deduplication and exclusion, 7 were included 

33Tong BMC Health Services Research 2018 

34 Lewnard CID 2021 
ACIP Meeting Summary February 23-24, 2022 

59

for GRADE. No PCV15 studies directly assessed VE against the critical outcomes. There were 

5 RCTs identified that evaluated PCV15 efficacy and/or safety in healthy children. All 5 studies 

were compared to those who received PCV13. The study by Platt in 2020 (V114-008) was a 

Phase 2 RCT that compared 2 different lots of PCV15 with PCV13 using a 3+1 schedule. Study 

V114-029 by Merck was a Phase 3 RCT in the pivotal study for PCV15, which was presented 

in-depth earlier in this session. As a reminder, this study evaluated PCV15 compared to PCV13 

using a 3+1 schedule, as well as concomitant vaccine administration with other routine 

immunizations. Study V114-027 by Merck evaluated product interchangeability with using 

PCV13 and PCV15. Study V114-024 by Merck evaluated catch-up schedules at different ages 

using PCV15. The fifth study, V114-031 by Merck was an RCT focused on safety and tolerability 

in healthy infants that was stratified between full-term and pre-term infants. Infants were given 

either PCV15 or PCV13 at 2, 4, 6, and 12-15 months of age. 

Regarding routine use in healthy children, PCV15 was non-inferior to PCV13 for all 13 shared 

serotypes post-dose 4. Post-dose 3 PCV15 was non-inferior to PCV13 for 12 of 13 shared 

serotypes, with serotype 6A missing the non-inferiority criteria. PCV15 had statistically 

significant higher immune responses for serotypes 3 and 22F and 33F—the 2 serotypes unique 

to PCV15. Immune responses for PCV15 were higher compared to PCV13 for serotype 3 and 

the unique PCV15 serotypes. The certainty assessment was not serious for all criteria except 

indirectness, which was downgraded to serious due to the absence of data on correlates of 

protection for some of the critical outcomes considered. The overall certainty of evidence was 

therefore 2 or Moderate. 

The WG determined that the desirable anticipated effects of routine PCV15 use are moderate. 

Considerations discussed by the WG include that no PCV15 studies directly assessed clinical 

outcomes. Additionally, there are knowns such as the clinical implications of improved 

immunogenicity against serotype 3. However, PCV15 provides additional coverage for 2 

additional serotypes compared with PCV13 if the improved immune response against these 2 

serotypes translates to clinical effectiveness. There were 5 RCTs that evaluated safety 

regarding PCV15 use in healthy children compared with PCV13 use. There were 5 SAEs 

reported following immunization in the intervention group across all 5 studies. A pooled estimate 

observed a higher risk for SAEs among the PCV15 group compared to the PCV13 group. 

However, this was not significant. Regarding the certainty assessment, all criteria were deemed 

not serious except precision, which was downgraded to serious due to few events of the 

outcome being reported. The overall certainty of evidence was 2 or Moderate. Therefore, the 

undesirable anticipated effects of routinely using PCV15 were determined to be minimal.

Balancing the desirable and undesirable effects, the WG determined that routine use of PCV15 

was favorable compared with the current recommendation. It should be noted that the vote was 

split between “favors intervention” and “favors both.” Some WG members thought the option 

“favors intervention” gave the impression that the WG was proposing a preferential 

recommendation when the intention was to assess whether PCV15 could be used as an option 

in addition to PCV13. Based on the certainty assessment during GRADE, routine use of PCV15 

was 2, moderate, for both effectiveness and safety of the intervention.

The WG identified 2 RCTs evaluating PCV15 use in children with underlying medical conditions 

compared with PCV13 use. The first study, V114-023, evaluated 1 dose of PCV15 in children 

with sickle cell disease. The second study, V114-030, evaluated PCV15 in series with PPSV23 

in children living with HIV. Regarding PCV15 use in children with underlying medical conditions, 

post-PCV dose, PCV15 had higher immune responses versus PCV13 for 6 to 7 PCV13 shared 

serotypes and unique serotypes 22F and 33F across both studies. In one study that assessed 
ACIP Meeting Summary February 23-24, 2022 

60

PCV use in series with PPSV23, post-PPSV23 dose, PCV15 plus PPSV23 had numerically 

higher immune responses versus PCV13 plus PPSV23 for 3 of 13 shared PCV13 serotypes, but 

not for unique serotypes 22F and 33F. When assessed for certainty of evidence, 2 of the criteria 

were downgraded. Indirectness was downgraded to serious due to the absence of data on 

correlates of protection for some critical outcomes considered, and imprecision was 

downgraded due to small sample size. Therefore, the overall certainty of evidence was 3, or 

Low. The WG determined that the desirable anticipated effects of PCV15 use in children

with underlying medical conditions is moderate.

WG discussions regarding this question were similar for both routine use in children less than 2 

years of age and use among children with underlying medical conditions. As a reminder, no 

PCV15 studies directly assessed clinical outcomes. The WG was split between “moderate” and 

“large,” with some uncertainty around the added benefit from PCV15 use, not just from 

additional serotypes, but also improved immune response against serotype 3. Additionally, there 

are unknowns such as the clinical implications of improved immunogenicity against serotype 3. 

However, as mentioned previously, PCV15 provides additional coverage for 2 additional 

serotypes compared with PCV13 if the improved immune response against these 2 serotypes 

translates to clinical effectiveness. In PCV15 use among children with underlying medical 

conditions, no SAEs following immunization were reported in either study. Regarding the 

certainty assessment, all criteria were deemed not serious except imprecision, which was 

downgraded twice to very serious, once due to no events of the outcome being recorded and 

again for very small sample sizes. Therefore, the overall certainty of evidence was 3, or Low.

The undesirable anticipated effects of using PCV15 in children with underlying medical 

conditions was determined to be “minimal.” Balancing the desirable and undesirable effects,

the WG determined that using PCV15 in children with underlying medical conditions was 

favorable compared with the current recommendation. As was discussed for routine use, it 

should be noted that the vote was split between “favors intervention” and “favors both.” Some 

WG members thought the option “favors intervention” gave the impression that the WG was 

proposing a preferential recommendation when the intention was to assess whether PCV15 can 

be used as an additional option to PCV13. Based on the certainty assessment during GRADE,

routine use of PCV15 in children with underlying medical conditions was 3, or Low, for 

effectiveness and 3, or Low, for safety of the intervention.

In terms of the domain of values and preferences, the WG considered the following questions:

 Does the target population feel that the desirable effects are large relative to undesirable 

effects?

 Is there important uncertainty about or variability in how much people value the main 

outcomes?

Data on values and preferences of PCV5 use in children were not identified. However, the WG 

looked at vaccination coverage for 3 or more doses of PCV by 24 months of age and found high 

vaccination coverage of 92.4%, demonstrating that the target population probably feels that the 

desirable effects of PCV vaccination outweigh the undesirable effects. The WG interpretation 

was split evenly between “probably yes” and “yes.” For PCV15 use, the WG agreed that the 

target population probably feels that the desirable effects from vaccination are large relative

to undesirable effects. The WG split in responses likely was due to the small potential added 

impact of PCV15 use over PCV13 use and not over the uncertainty about whether the vaccine 

is able to prevent serious pneumococcal disease. For the second question, the WG determined 
ACIP Meeting Summary February 23-24, 2022 

61

that there is “probably not important uncertainty or variability” in how people value the main 

outcomes.

For the last domain of equity, the WG considered what the impact would be on health equity. To 

answer this question, the WG looked at unadjusted IPD rates using ABCs data from 2008-2019 

in 2-year increments for children less than 5 years of age, those 5-18 years of age, and for 

different serotype groupings. For all serotypes, rates decreased during and after 2010 in both 

age groups and were sustained over time except in Black children 5-18 years of age. However, 

it is important to note the small IPD rates in children aged 5-18 years. Rate ratios comparing 

Black and White children decreased from the start to the end of the study period in children less 

than 5 years of age but not in children 5-18 years of age, although both sets of rates went down. 

Decreases in overall rates were driven by decreases in PCV13 serotypes. Overall decreases in 

PCV13-type IPD in all groups were observed from the start to the end of the study period. Rate 

ratios in children less than 5 years of age decreased over the study period, but in children 5-18, 

ratios did not, although rates went down in both groups. Non-PCV13 rates remained fairly stable 

over time in White children but decreased from 14 per 100,000 to 8 per 100,000 in Black 

children less than 5 years of age, causing the rate ratio to decrease. Rates went up in Black 

children 5-18 years of age, although the rates were much smaller compared to younger 

children. There were not big differences by race in the PCV15 non-PCV13 serotypes at any 

point over the study period.

In conclusion, racial differences in PCV15 non-PCV13-types were quite small. PCV13 resulted 

in large reductions in IPD in both age groups across races. Regarding equity in Native American

and Alaska Native children, IPD rates among Native American children less than 5 years of age 

decreased after PCV13 use, but rates remained approximately 4-fold higher than in children of 

all races.35 Data on Alaska Native children showed that Alaska Native infants had a 1.6-fold 

higher rate of otitis media-associated outpatient visits compared to all infants36 and Native 

American and Alaska Natives experienced cyclical outbreaks due to serotype 12F,37 which is 

not included in PCV13, but is included in PPSV23. Regarding equity in vaccination coverage, 

foreign-born children aged 19-35 months of age had significantly lower coverage rates 

compared to US-born children.38 Comparing PCV coverage rates for 4 or more doses, fewer 

Native American children aged 19-35 months were up to date when compared to White children 

in a study in North Dakota.39 Looking at National Immunization Survey (NIS) data from 2020, 

PCV coverage of 4 or more doses by 24 months of age is low among children who are 

uninsured, Black, non-Hispanic, living in a non-metropolitan statistical area (MSA), or living in 

the lowest federal poverty level. The WG determined that recommended PCV15 probably would 

increase equity. It should be noted that the WG was split in responses, with some voting for 

“probably no impact,” which is likely due to uncertainty regarding whether PCV15 use will 

improve health equity compared to PCV13 use.

In summary, the WG determined that pneumococcal disease is of public health importance in 

children. Regarding benefits and harms, the WG determined that desirable anticipated effects 

are moderate and undesirable anticipated effects are minimal. The WG determined that using 

PCV15 was favorable compared to PCV13. But as previously noted, the option “favors 

intervention” gave the impression that a preferential recommendation was being proposed when 

the intention was to assess whether PCV15 can be used as an option in addition to PCV13. The 

35 Littlepage et al, 9th International Meeting on Indigenous Child Health, 2021 36 Singleton et al. PIDJ 2018 

37 Zulz et al. JCM 2012 

38 Varan, AK et al. 2017. J Immigr Minor Health

39 Woinarowicz, M & Howell, M. 2020. Public Health 
ACIP Meeting Summary February 23-24, 2022 

62

overall certainty of evidence regarding VE for routine use in children less than 2 years of age 

was 2 or Moderate. Indirectness was downgraded once to serious due to lack of data on 

correlates of protection for some critical outcomes considered. Regarding children 2-18 years of 

age with underlying medical conditions, overall certainty for VE was 3, or Low. Indirectness was 

downgraded once to serious due to absence of data on correlates of protection for some critical 

outcomes considered, and imprecision was downgraded once to serious due to small sample 

size. Overall certainty for safety was 2, or Moderate, for routine use in children less than 2 years 

of age, with imprecision downgraded once to serious due to few events of the outcome being 

recorded. For children with underlying medical conditions, overall certainty of evidence for 

safety was 3, or Low. Imprecision was downgraded twice to very serious, once due to no events 

of the outcome being reported, and again for very small sample sizes. Regarding values and 

preferences, the WG agreed that the target population probably feels that the desirable effects 

from vaccination are large relative to undesirable effects. Additionally, the WG determined that 

there is probably not important uncertainty or variability in how people valued the main 

outcomes. Lastly, the WG determined that recommending PCV15 probably would increase 

equity.

Discussion Summary

Miss Bahta requested additional information about the discussion of determining that equity 

would be increased and whether that was because there would be another product that could 

be used. 

Dr. Kobayashi clarified that the WG responses were split across the options. The option that 

had the highest number of votes was the one that was presented—that probably equity would 

be increased. The thought was that though the incidence in IPD rates between Black and White 

populations due to the 2 additional serotypes included in PCV15 was different, it provides an 

opportunity to prevent more disease with the additional serotypes included. By having that 

product and preventing more disease, the thought was that there would be an opportunity to 

prevent more disease in general and that there is a possibility that this might improve equity.

She emphasized that there were opinions suggesting different options as well. The option of 

“probably increased” comprised the majority of opinions.

Dr. Sanchez expressed surprise about the suggestion that it would be an optional rather than a 

preferential recommendation. With 2 additional serotypes, a good safety profile, and 

immunogenicity data that are supportive of a benefit, it seemed that there would be an option for 

a preferential recommendation. With PCV15, it is possible that PCV13 would not be 

manufactured anymore at some point.

Dr. Poehling pointed out that to have a preferential recommendation, there would need to be a 

comparison of clinical outcomes and the WG had only immunogenicity data. For that reason,

the WG acknowledged the data and that there would be an option.

Dr. Daley asked whether the WG discussed any concern about the idea that 2-month-olds may 

get a high enough fever that they present for medical care and have a septic workup. Obviously, 

there was a lot of supportive data and the differences were small. He was just struck by 2 

aspects of the prior presentation. One was that there were 2 SAEs in the PCV15 group and the 

reason they were deemed serious was because the children had a fever and then presented

and were admitted to the hospital for that fever. There were 0 fevers in the PCV13 group. Even 

recognizing that the sample sizes were different, it seems like there might be some imbalance
ACIP Meeting Summary February 23-24, 2022 

63

and somewhat higher fever in the older children that potentially could lead to febrile seizures. It 

seemed like an area to which additional attention should be paid.

Drs. Kobayashi and Poehling indicated that the WG did not specifically discuss this point. Dr. 

Poehling added that the WG did not see a difference between PCV13 and PCV15 in those 

young children, so that also drove that decision.

Dr. Maldonado (AAP) commented that whatever the outcome of this vote in the future, the 

Committee on Infectious Diseases (COID) of the AAP agreed with and approved of using the 

remaining pneumococcal vaccination doses and that no changes to dosing or schedules would 

be needed. She also emphasized that the equity data are not new and have been persistent 

over many years that underserved, diverse, and vulnerable populations tend to have lower 

vaccination rates for the 3+1 schedule and COID/AAP are appreciative of and recommend the 

strong consideration to leave the dose/schedule intact at this point. 

Summary and Next Steps

Dr. Miwako Kobayashi (CDC/NCIRD) presented the Pneumococcal Vaccines WG’s next 

steps. As discussed during this session’s presentations, the policy questions on PCV15 use in 

children are: 

 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 U.S. children with underlying medical conditions 2–18 

years of age as an option for pneumococcal conjugate vaccination according to currently 

recommended dosing and schedules?

Evidence reviewed by the WG and presented to ACIP during this session included data on the 

epidemiology of pneumococcal disease and vaccine-preventable disease burden for IPD, 

pneumonia, and AOM; immunogenicity and safety data of PCV15 in children from Phase 2/3 

studies; and the GRADE and EtR framework to summarize the evidence and the WG 

interpretation on the EtR domains of the public health problem, benefits and harms, values, and 

equity. In future WG meetings, WG members will review the expected public health impact and 

cost-effectiveness of PCV15 use in children and will summarize the WG’s interpretation of the 

remaining EtR domains of resource use, acceptability, and feasibility and will update the WG’s 

interpretation for other domains, if indicated.

The WG also will review data to inform clinical guidance for PCV15 use, such as use of PCV15

in children who are incompletely or completely vaccinated with PCV13. Additional data will be 

summarized and presented during the June ACIP meeting, along with policy options on PCV15 

use in children for consideration for a vote if the product is licensed for use. The following 

questions were posed for ACIP’s consideration:

 Does the committee agree with the policy questions being considered by the WG?

 Are there additional data the committee would like to see before deciding on policy options 

for a vote?
ACIP Meeting Summary February 23-24, 2022 

64

Discussion Summary

Ms. McNally asked for this particular recommendation whether PCV15 would be considered as 

an option to PCV13 for pneumococcal conjugate vaccine administration and if it would be up to 

the provider to determine which product to carry. In addition, she wondered how parents would 

be educated about the difference in order to be able to determine what they want to select for 

their children. 

Dr. Kobayashi indicated that the WG is still reviewing the remainder of the EtR domains and are 

happy to raise these questions for discussion. There are precedents with other vaccines such 

as human papillomavirus (HPV) in which different valency vaccines have been on the market, 

so this situation would not be unique to the pneumococcal conjugate vaccine.

Dr. Sanchez added that the question of which vaccine to carry depends on whether there is a 

preferential recommendation. Given that there is no invasive data, it does not make much sense

on a practical basis to have a preferential recommendation. He thought ultimately providers

would want to know that it may be an option to use one or the other, but that there may be 

benefits otherwise to including more serotypes.

Dr. Long indicated that as a member of this august WG, she had not commented. However, she 

thought she understood how the ACIP members were thinking. It is important to remember that 

the majority of IPD currently occurring is due to serotypes that are in the currently available

vaccine. That is, this vaccine theoretically increases coverage for 17% of invasive disease.

What is not known as serotypes continue to be added are the potential impact and/or 

unintended consequences on colonization or on the serotypes for which there already is good 

clinical evidence of superb efficacy with the existing vaccine. In terms of the equity issue, there 

are only 4300 infants in the safety studies. This raised the same considerations and concerns

she raised earlier regarding the critical questions about high fevers in the PCV15 group that 

would not be explained by concurrent MMRs since these were fevers in the first week.

Therefore, there is more work to do. As far as equity is concerned, it seems that there would 

need to be a lot more antibody to serotype 3 in addition to the 2 additional serotypes in PCV15 

to have the expected clinical impact. That is a complete unknown. Looking at who is getting IPD 

with the 2 additional serotypes, it would be expected to see more common occurrence in Black 

compared with White populations, as all IPD was before there were pneumococcal conjugate 

vaccines. She would not be in in favor of preferentially approving a vaccine just because it 

contains more serotypes. It is unknown whether there may be a “tipping point” for what happens 

in the ecology of the nasopharynx because pneumococcus had had a spot there forever. Until 

these vaccines are in use, it is unclear what replacement might occur. Therefore, she thought 

caution would be in order. Parents would not need to make a decision about what is best for 

their children if ACIP ultimately voted that these 2 pneumococcal conjugate vaccines are not 

different enough to make one preferred over the other. Instead, doctors would carry what works 

best for their practice.

Dr. Loehr noted that when there was a new HepB vaccine, ACIP did not vote on it because it 

was fit into the schedule. It seemed that because this was not a new PCV13 vaccine, ACIP 

would need to vote to approve it and recommend how it should be used.

Dr. Kobayashi confirmed that Dr. Loehr’s observation was correct.
ACIP Meeting Summary February 23-24, 2022 

65

Dr. Lee agreed that the policy questions seemed very appropriate. She noted that the high-risk 

populations and the data that was determined to be Level 3 made sense to her, but asked if the 

WG discussed whether those differences were felt to be meaningful for high-risk children. She 

clarified that her question was less about the GRADE itself and more about the potential

difference in immunogenicity, at least for a subset of those serotypes and whether that had any 

clinical meaning to the WG members to suggest that ACIP should think about it differently for

the high-risk population versus the healthy population.

Dr. Kobayashi indicated that there were no specific concerns raised among WG members about 

whether this vaccine would work differently in this population. However, that was based on the 

available data for this population suggesting that the efficacy might be comparable to what is 

observed from PCV13 use in this population. The WG also reviewed data on the VE of PCV13, 

which were limited among children with an underlying condition.

In terms of vaccines in general, Dr. Maldonado acknowledged the polio vaccine workers who 

were killed in Afghanistan the previous week as part of their unrelenting service to the world and 

children throughout the world in their efforts to eradicate polio.
ACIP Meeting Summary February 23-24, 2022 

66

CERTIFICATION

Upon reviewing the foregoing version of the February 23-24, 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 February 23-24, 2022 

67

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 Medicin

Stanford, CA 

Term: 8/4/2021 – 6/30/2023

e 

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 Divisio

Minnesota Department of Health 

Saint Paul, Minnesota 

Term: 7/1/2019 – 6/30/2023

n 

 

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 February 23-24, 2022 

68

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 February 23-24, 2022 

69

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 February 23-24, 2022 

70

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 February 23-24, 2022 

71

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 February 23-24, 2022 

72

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 February 23-24, 2022 

73

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 February 23-24, 2022 

74

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 February 23-24, 2022 

75

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 February 23-24, 2022 

76

ACRONYMS USED IN THIS DOCUMENT

 

AAFP American Academy of Family Physicians 

AAP American Academy of Pediatrics

ABCs Active Bacterial Core Surveillance 

ACA Affordable Care Act 

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 

AHA American Heart Association

AHIP America’s Health Insurance Plans

AI/AN American Indian/Alaskan Native 

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 

CDC Centers for Disease Control and Prevention

CHIP Children’s Health Insurance Program 

CICP Countermeasures Injury Compensation Program 

CMS Center for Medicare and Medicaid Services

COI Conflict of Interest 

CSF Cerebrospinal Fluid 

CSTE Council of State and Territorial Epidemiologists 

DFO Designated Federal Official

DoD Department of Defense

DSMB Data Safety Monitoring Board 

DVA Department of Veterans Affairs

ECL Electrochemiluminescence 

ED Emergency Department

EIP Emerging Infections Program 

ELISA Enzyme-Linked Immunosorbent Assay

EMR Electronic Medical Record 

EPSDT Early and Periodic Screening, Diagnostic and Treatment 

ESRD End-Stage Renal Disease 

ET Eastern Time
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EtR Evidence to Recommendation 

EUA Emergency Use Authorization 

EVs Enhanced Vaccines 

FDA Food and Drug Administration

FRN Federal Register Notice 

GBS Guillain-Barré Syndrome 

GMR Geometric Mean Ratio 

GMT Geometric Mean Titers 

GRADE Grading of Recommendation Assessment, Development and Evaluation 

HCP Healthcare Personnel / Providers

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 

IDSA Infectious Disease Society of America 

IHS Indian Health Service 

IIS Immunization Information System 

IPD Invasive Pneumococcal Disease 

IV Intravenous

MMWR Morbidity and Mortality Weekly Report

MSA Metropolitan Statistical Area 

NACCHO National Association of County and City Health Officials 

NACI National Advisory Committee on Immunization Canada

NAPNAP National Association of Pediatric Nurse Practitioners 

NCEZID National Center for Emerging and Zoonotic Infectious Diseases 

NCHS National Center of Health Statistics 

NCIRD National Center for Immunization and Respiratory Diseases 

NFID National Foundation for Infectious Diseases 

NHSN National Healthcare Safety Network 

NIH National Institutes of Health

NIS National Immunization Survey 

NMA National Medical Association 

NP Nasopharyngeal Swab 

NVAC National Vaccine Advisory Committee 

NVPO National Vaccine Program Office 

OASH Office of the Assistant Secretary for Health 

OAW Operation Allies Welcome 

OIDP Office of Infectious Disease and HIV/AIDS Policy (OIDP)

OPA Opsonophagocytic Activity 

PHAO Pan American Health Organization 

PCP Primary Care Provider/Practitioner

PCR Polymerase Chain Reaction

PHAC Public Health Agency Canada 

PICO Population, Intervention, Comparison, Outcomes

PIDS Pediatric Infectious Disease Society 

RCT Randomized Controlled Trial

RIV Recombinant Influenza Vaccine 
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SAE Serious Adverse Event 

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

SVs Standard Vaccines 

US United States

USG United States Government

VAERS Vaccine Adverse Event Reporting System

VE Vaccine Efficacy

VE Vaccine Effectiveness

VFC Vaccines For Children 

VICP National Vaccine Injury Compensation Program 

VSD Vaccine Safety Datalink

WG Work Group

WHO World Health Organization