MEETING OF THE ADVISORY 

COMMITTEE ON IMMUNIZATION 

PRACTICES (ACIP)

JANUARY 12, 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

CHOLERA VACCINE ................................................................................................................ 4

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

Vaxchora® Pediatric Dose Development ............................................................................... 4

EtR Framework: CVD103-HgR among Children and Adolescents 2-17 Years of Age.......... 6

Discussion Summary ...........................................................................................................11

TICKBORNE ENEPHALITIS (TBE) VACCINE........................................................................13

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

Immunogenicity of 1 or 2 Doses of TBE Vaccine ................................................................14

EtR Framework for Travelers & Laboratory Workers...........................................................15

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

INFLUENZA VACCINE............................................................................................................26

Session Introduction ............................................................................................................26

Influenza Vaccines for Older Adults.....................................................................................26

Discussion Summary ...........................................................................................................35

HEPATITIS VACCINE .............................................................................................................36

Session Introduction ............................................................................................................36

Safety & Immunogenicity of a 3-Antigen Hepatitis B Vaccine, PreHevbrioTM......................36

Discussion Summary ...........................................................................................................40

MATERNAL/PEDIATRIC RESPIRATORY SYNCYTIAL VIRUS (RSV) WG ...........................41

PNEUMOCOCCAL VACCINE................................................................................................. 42

Session Introduction ............................................................................................................42

Updates from the Pneumococcal Vaccines WG..................................................................43

PUBLIC COMMENT ................................................................................................................47
ACIP Meeting Summary January 12, 2022

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CERTIFICATION.........................................................................................................................................53

ACIP MEMBERSHIP ROSTER...................................................................................................................54

ACRONYMS USED IN THIS DOCUMENT................................................................................................. 63
ACIP Meeting Summary January 12, 2022

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MEETING PURPOSE

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

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

Immunization Practices (ACIP) on January 12, 2022. The meeting took place remotely via 

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

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

syncytial virus (RSV), and pneumococcal vaccines; 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 January 12, 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 3:10 PM Eastern Time (ET) on 

January 12, 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-2022-0132. 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 January 12, 2022

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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?” This session focused on Vaxchora®

pediatric dose development and the Evidence to Recommendation (EtR) Framework for 

CVD103-HgR among children and adolescents 2-17 years of age.

Vaxchora® Pediatric Dose Development

James McCarty, MD (Emergent BioSolutions) presented a brief overview of recent studies 

addressing pediatric dosing volume and palatability of the live attenuated V. cholerae vaccine, 

Vaxchora®. Vaxchora® is composed of 2 packets, or sachets, that are reconstituted in bottled 

water prior to administration. The first of the 2 packets contains a buffer powder that neutralizes 

stomach acid and facilitates the passage of vaccine into the intestines. The second packet 

contains the active component, which is comprised of 2 grams of lyophilized V. cholerae

CVD103-HgR vaccine strain. Vaxchora® has been evaluated in a Phase 1 study and several 

randomized double blind placebo controlled Phase 3 and 4 trials in over 4,000 subjects aged 2-

64 years of age. Objectives have included safety, immunogenicity, shedding, and clinical 

efficacy. In the Phase 3 challenge study, seroconversion was noted in most subjects by 7 days 

after immunization and demonstrated 90.3% efficacy at 10 days and 79.5% efficacy at 3 

months, versus placebo against challenge with a virulent strain of V. cholerae. A second Phase 

3 study documented lot-to-lot consistency and the third Phase 3 study demonstrated a similar 

immune response in older adults compared with younger adults. A Phase 4 study demonstrated 

that Vaxchora® is well-tolerated and safe in children aged 2-17 years, with seroconversion 

occurring in 98.5% of subjects by 10 days post-vaccination—a seroconversion rate that is noninferior to vaccine in adults.

The pediatric dose development plan was designed to adapt the vaccine to children aged 2-6 

years. The primary goals of the product development studies presented during this session 

were to use the existing approved Vaxchora® formulation as described and to adapt the vaccine

to children 2-6 years of age by reducing the administration volume and masking the taste. The 

methods used were to reduce the administration volume from 100 mL to 50 mL and to 

investigate the compatibility of different flavoring options and taste masking strategies with

Vaxchora®. The first step in the development of the Vaxchora® pediatric dose was to reduce the 

volume. Several reconstitution methods were tested, including simply adding the buffer and 

active component to 50 mL of water instead of the 100 mL prescribed for the approved vaccine 

in adults. Reconstituting the full buffer into 50 mL of water resulted in a pH of 7.16, which is 

above the release specification. Reconstituting the full buffer and vaccine components directly 

into 50 mL of water resulted in a slight drop in vaccine potency. An alternative was to 

reconstitute the buffer in 100 mL of water followed by discarding half and reconstituting the 

entire active component in the remaining 50 mL of buffered water. In this case, the buffering 

capacity was below specification and half of the reconstituted buffer was discarded.

When using this method, the Vaxchora® solution remained within the potency specification for 

at least 15 minutes. The reduction in buffering capacity was deemed acceptable because 

children have a lower gastric volume and higher gastric pH than adults. This is the dose method 
ACIP Meeting Summary January 12, 2022

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that was used with children 2-6 years of age in the pediatric trial, which resulted in high 

seroconversion rates and which was approved by the FDA for use in children. It was concluded 

from these results that the buffer should be kept at the same concentration as the adult 

formulation and that Vaxchora® is stable when reconstituted in this way in 50 mL of buffer water.

There was an option to add a sweetener (e.g., sucrose or Stevia), which was stirred into the 

reconstituted vaccine and then the vaccine was consumed within 15 minutes. The next step in 

the development of Vaxchora® pediatric dose was to investigate the compatibility of different 

flavoring options and taste-masking strategies. Over-the-counter flavoring agents, such as 

FLAVORx® or Yummy Meds®, contained propylene glycol which has shown to be bactericidal. 

Data documented Vaxchora® colony counts well below the lower limits of specification when 

FLAVORx® was added to the vaccine mixture. During the pediatric study, only PURE VIA Stevia

sweetener was used to flavor the vaccine. Therefore, a more thorough study of the compatibility 

of Vaxchora® with sucrose and different brands of Stevia was performed. Stevia is much 

sweeter than sugar, so fillers are used to add bulk and the Stevia itself generally accounts

for less than 5% of the sweeteners by weight. The strategy in the laboratory was to choose 

Stevia brands that are available worldwide and contain the most commonly used fillers. An 

online search showed that the Stevia market is consolidated and dominated by just a few 

players, including Cargill (makers of Truvia®) and Tate and Lyle (makers of Splenda®). The most 

commonly used fillers of popular brands are inulin, erythritol, maltodextrin, and dextrose.

Representative brands of Stevia® powder or Stevia® crystals were chosen to include popular 

brands and the most common filler ingredients. One gram of Stevia®, which is equivalent to 1 

packet bought in the store or 4 grams of sucrose were added to 50 mL of reconstituted

Vaxchora® and the potency was tested after 15 minutes. Vaxchora® potency was maintained in 

the presence of sucrose in all brands of Stevia® tested. The conclusion was that Vaxchora® is 

well-tolerated and likely effective in children aged 2-17 years. Vaxchora® is compatible with up 

to 4 grams of sucrose or Stevia® sweeteners in a reconstitution volume of 15 mL. It is 

compatible with Stevia® brands available around the world, including their common fillers. 

Vaxchora® should not be used with medicine flavorings, such as FLAVORx® or Yummy Meds®

due to the presence of propylene glycol. 

Discussion Summary

Dr. Hogue (APhA) emphasized that pharmacists are always interested in how they can help

pediatric patients take medicines and vaccines, so flavoring is very important. While an image 

was shown of the reconstitution instructions for the pediatric formulation, there was no mention 

of whether sweetener could be added to the adult dose. Some adult patients have certain taste 

aversions as well, so he wondered whether it be acceptable to add sweetener to the adult

product or if there were any concerns about doing so. He also requested clarity with regard to 

whether a pharmacist, nurse, or physician would be able to use an off-the-shelf packet of 

Stevia, Truvia®, or a similar sweetener, or if the manufacturer would supply a sweetener with the 

product. 

Dr. McCarty said that with the caveat that he did not know the exact language submitted in 

terms of the label, he knew of no reason that there would be any issues with adding stevia or 

sucrose to the adult 100 mL mixture based on the laboratory data generated thus far. There are 

no plans at this time for the manufacturer to provide a sweetener with the product.
ACIP Meeting Summary January 12, 2022

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Dr. Poehling pointed out that when parents present to a travel clinic, they will sometimes have 

multiple children in this age group. In terms of product distribution, she could imagine a scenario 

in which buffer might be added to 100 mL of water and divided into 50 mL to which vaccine 

would be added for each of 2 children instead of any being discarded. She wondered whether 

that would be considered to enhance efficiency.

Dr. McCarty clarified that each container of vaccine has 2 sachets, 1 that contains the buffer 

and the other that contains the vaccine, so 2 sachets of Vaxchora® would still be used to 

immunize 2 children. Dividing 100 mL into 2 equal 50-milliter containers of buffer solution and 

adding a complete vaccine sachet into each container should not be a problem.

Dr. Kim (OIDP) observed that while Vaxchora® is anticipated to be recommended for children 2-

17 years of, the child and adolescent immunization schedule goes through 18 years of age and 

the adult immunization schedule begins at age 19. It was not clear where those 18 years of age 

would fit into the recommendations and whether there were considered to be similar to 

individuals 16-17 years of age.

Dr. McCarty indicated that the same product was used in the adult studies ≥18 years of age. 

The data have consistently supported safety and immunogenicity in subjects aged 16, 17, 18,

and 19 years. The cutoff and recommendation language would be up to ACIP to determine.

Dr. Schneider (Emergent BioSolutions) added that in accordance with the label, Vaxchora® is

indicated for persons 2-64 years of age.

Dr. Daley clarity about whether the amendment submitted to the FDA was only for the purpose 

of amending the package insert to specify the types of sweeteners that could be used. 

Dr. McCarty clarified that the purpose was not only to specify the types of sweeteners that could 

be used, but also the type of water.

Dr. Lee asked whether there was any intent to create a specific set of sachets for children 2-6 

years of age, which could minimize administration errors in high volume clinics.

Dr. McCarty indicated that at this time, the intent is to continue to use the same manufacturing 

process and formulation.

EtR Framework: CVD103-HgR among Children and Adolescents 2-17 Years of Age

Jennifer Collins, MD, MSc (CDC/NCEZID/DFWED) presented the EtR Framework for 

CVD103-HgR among children 2-17 years of age. Regarding the background of the WG, in June 

2016 ACIP recommended the cholera vaccine CVD103-HgR (renamed Vaxchora®) for adult 

travelers aged 18-64 years from the US to an area with active cholera transmission. This is the 

only cholera vaccine licensed for use in the US. In October 2020, the current ACIP Cholera 

Vaccine WG formed. In December 2020, FDA extended the approved usage of Vaxchora® to 

include children and adolescents aged 2-17 years. In February 2022, the WG presented

background information and the manufacturer presented pediatrics clinical trial data. The 

current policy question under consideration is. “Should ACIP recommend CVD 103-HgR for 

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

transmission?” 
ACIP Meeting Summary January 12, 2022

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The components of the PICO question include the population of children and adolescents aged 

2-17 years traveling to an area with active cholera transmission. The intervention is lyophilized 

CVD 103-HgR, a single dose, oral, live attenuated bacterial vaccine. The comparison is no 

cholera vaccine. The WG identified 4 outcomes as the most important for this question, 

including cholera diarrhea (moderate or severe), cholera diarrhea (any severity), serious 

adverse events (SAEs), and non-SAEs. 

The WG identified the following primary question and sub-questions for the first EtR domain, 

public health problem:

 Is cholera among children and adolescents aged 2–17 years traveling to an area with active 

cholera transmission a public health problem?

− Are the consequences cholera serious (i.e., severe or important in terms of the 

potential benefits or savings)?

− Is cholera urgent?

− Are many travelers aged 2–17 years from the US affected by cholera?

− Is cholera related to emerging diseases, antimicrobial resistance, or epidemic 

potential?

− Are disadvantaged groups or populations disproportionately/differentially affected by 

cholera?

Infection with toxigenic V. cholerae 01 can cause a range of symptoms. Although most 

infections are asymptomatic, mild, or moderate, up to 10% of infections manifest as cholera 

gravis—the most severe form of cholera. Cholera gravis is rapidly fatal if untreated. Fluid 

management is the primary focus of treatment and rehydration can reduce the fatality rate to

less than 1%. However, patients with cholera gravis may require up to 350 ml/kg of fluids within 

the first 24 hours of illness. Most international travelers from the US do not get cholera because 

they do not visit areas with active cholera transmission and they have good access to safe food 

and water. During 2012-2018, there were 64 cholera cases reported in the US. Among these 

cases, 5 patients (8%) were aged 2-17 years. There were 2 deaths in adults and there were 56 

(88%) travel-associated cases. However, national cholera case counts underestimate the true 

burden of illness given limitations inherent in surveillance for laboratory-confirmed infections.

Antibiotic resistance (AR) can occur among the bacteria causing cholera; however, fluids are

the mainstay of treatment. Antibiotics are adjunctive therapy in moderate to severe illness. An 

estimated 1.3 to 4 million cholera cases and 21,000 to 143,000 cholera deaths occur worldwide 

each year.1 Cholera epidemics are associated with unsafe water and inadequate sanitation. 

Secondary cases are rare if sanitation is adequate. Therefore, a US outbreak from a returning 

traveler is unlikely.

The work group deliberated whether cholera is a public health problem among children and 

adolescents aged 2-17 years traveling to an area with active cholera transmissions. WG 

members agreed that cholera is a public health problem for local populations in endemic

settings due to unsafe drinking water and inadequate sanitation. However, for travelers from the 

US, WG members felt that even within cholera endemic areas, the risks for travelers varied by

travel destination; travel activities such as tourism versus visiting friends and relatives and 

access to safe food; water, and sanitation. Apart from the public health question, members

noted that cholera may pose a meaningful individual risk for ill travelers with inadequate or 

delayed access to fluid replacement therapy—even in instances when there is risk of secondary 

transmission as well. Finally, cholera may become a bigger problem for travelers in the future. 

1 https://www.who.int/health-topics/cholera#tab=tab_1 
ACIP Meeting Summary January 12, 2022

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The WG agreed that having a supply of cholera vaccine for US travelers is important. For the 

public health problem domain, most WG members felt the determination should be “probably 

yes,” though some felt it should “probably no” or “varies.” The final WG consensus was 

“probably yes.” 

The WG determined the questions for the next EtR domain, benefits and harms, to be as 

follows:

 How substantial are the desirable anticipated effects overall and for each main outcome for 

the desirable effect? 

 How substantial are the undesirable anticipated effects overall and for each main outcome 

for which there is an undesirable effect?

 Do the desirable effects outweigh the undesirable effects?

 What is the overall certainty of this evidence for the critical outcomes?

The WG categorized the PICO outcomes as benefits and harms. Prevention of cholera diarrhea

(moderate or severe) and prevention of cholera diarrhea (any severity) were rated as critical 

benefits. For harms, SAEs were rated as critical and non-SAEs were rated as important. A 

systematic review was conducted to identify evidence and use of CVD 103-HgR among children

and adolescents aged 2-17 years. Published articles were identified using several databases

(PubMed, Embase, and Cochrane Library) and search terms (cholera, Vibrio cholerae, CVD 

103-HgR, cholera vaccine). Studies were included if they provided data on the current

formulation and dose of the vaccine, involved human subjects aged 2-17 years, reported 

primary data relevant to the efficacy and safety outcomes, and were conducted in cholera nonendemic settings. Titles and abstracts were screened by 2 reviewers. Overall, 571 records were 

identified and screened and 3 studies were included in the GRADE (Grading of 

Recommendation Assessment, Development and Evaluation review). 

Three articles summarized a Phase 4 randomized double-blind placebo-controlled trial among 

children and adolescents aged 2-17 years. Results of the clinical trial were presented to ACIP

by the manufacturer in February 2021. In summary, the study setting was 7 US sites from July 

2017 through December 2019. The sponsor enrolled healthy children and adolescents aged 2-

17 years, divided into 3 age cohorts: Cohort 1: 12-17 years; Cohort 2: 6-11 years; Cohort 3: 2-5 

years. Participants were randomized using a 6:1 ratio to receive the vaccine at 1x109 CFU vs. 

0.9% saline placebo. Participants or parents could request an optional sweetener for 

palatability, which was PureVia brand Stevia. At least 92% of participants in each study arm 

chose this. The relevant outcomes addressed included safety and immunogenicity.

Regarding outcomes 1 and 2, cholera diarrhea (moderate to severe) and cholera diarrhea (any 

severity), no pediatric studies directly assessed vaccine effectiveness (VE). Assessment of

these outcomes was based on immunobridging to adults and immune efficacy has been 

demonstrated. In a separate study, wild-type Vibrio cholerae 01 was administered to 

participants aged 18-45 years following vaccine or placebo. The correlation coefficient between 

cumulative diarrhea in liters and fold-increase in serum vibriocidal antibodies was -0.75 at 10 

days and -0.69 at 3 months. Separately in endemic settings, fold-increases in SVA correlated

with protection in both adults and children.
ACIP Meeting Summary January 12, 2022

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In terms of the GRADE evidence table for cholera diarrhea (moderate to severe) and cholera 

diarrhea (any severity), 2 randomized control trials (RCTs) were included and the evidence 

certainty began at Type 1. The WG downgraded the evidence for serious indirectness because 

efficacy is inferred from immunobridging. The full effects demonstrate that seroconversion was 

more likely in vaccine recipients than among placebo recipients. The final certainty was Type 2,

or Moderate. The GRADE evidence table for SAEs included 2 RCTs and the evidence certainty 

began at Type 1. No SAEs were attributed to the vaccine in either study. The WG downgraded 

the evidence for very serious imprecision based on the small sample size to assess SAEs, the 

small number of events, and the wide 95% confidence intervals that crossed the line of no 

effect. The final certainty was Type 3, or Low. The GRADE evidence table for non-SAEs was 

assessed by any solicited AE from study Days 1-8. Again, 2 RCTs were included and the 

evidence certainty began at Type 1. The WG downgraded the evidence for very serious 

imprecision based on the wide confidence interval that crossed the line of no effect. The final 

certainty was Type 3, or Low.

To summarize the GRADE evidence for the critical benefits of cholera diarrhea (moderate to 

severe), CVD 103-HgR effectively induces SVA seroconversion, an imperfect correlate of 

protection against cholera. The final evidence was Type 2, or Moderate. For the critical harm of 

SAEs, none were judged to be related to the vaccine and the final evidence was Type 3, or Low.

Finally, the frequency of non-SAEs was not meaningfully different among vaccine versus

placebo recipients and the final evidence was Type 3, or Low, for this important outcome. The 

WG felt that the desirable anticipated effects were moderate, the undesirable anticipated effects

were small, and the balance between desirable and undesirable effects favored the intervention, 

CVD 104-HgR. The overall certainty of this evidence for this critical outcome was Type 3, or 

Low.

The WG next reviewed the domain of values, for which the following questions were 

determined:

 Does the target population feel the desirable effects are large relative to the undesirable 

effects?

 Is there important uncertainty about, or variability in, how patients value the outcomes?

For values, no research evidence was identified. The WG noted that cholera vaccines are

optional and individuals can decide whether to get vaccinated based on their values. Therefore, 

the WG’s determination for values was “Don’t know.”

Turning to the domain of acceptability, the WG considered the following question and subquestions:

 Is the intervention acceptable to key stakeholders?

− Are there key stakeholders who would not accept the distribution of benefits, harms, 

and costs?

− Are there key stakeholders who would not accept the costs or undesirable effects in 

the short-term for the desirable effects in the future?

For acceptability, no research evidence was identified. However, the WG noted that travel 

medicine providers and medical associations, such as the Infectious Diseases Society of 

America (IDSA), the American Academy of Pediatrics (AAP), and the Pediatrics Infectious 

Diseases Society (PIDS) are likely to find it acceptable to administer CVD 103-HgR to children 
ACIP Meeting Summary January 12, 2022

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and adolescents aged 2-17 years traveling to an area with active cholera transmission. The 

WG’s determination for acceptability was “Yes.”

The WG determined the following primary question and sub-questions for the domain of 

resource use:

 Is CVD 103-HgR among children and adolescents aged 2-17 years traveling to an area with 

active cholera transmission a reasonable and efficient allocation of resources?

− What is the cost-effectiveness of the vaccination?

− How does the cost-effectiveness of the vaccination vary in any sensitivity analyses?

− How does the cost-effectiveness change in response to changes in context, 

assumptions, model structure, across different studies, etc.?

For research use, no research evidence was identified. A cost analysis was not conducted given 

the optional nature of the vaccine among travelers. For research use, the WG determination 

was “Don’t know.”

The main question and sub-questions identified by the WG to assess equity included the 

following:

 What would be the impact on health equity of CVD 103-HgR among children and 

adolescents aged 2-17 years traveling to an area with active cholera transmission?

− Are there any groups or settings that might be disadvantaged in relation to the 

problem or options that are considered?

− Are there plausible reasons for anticipating differences in the relative effectiveness of 

the option for disadvantaged groups or settings?

− Are there different baseline conditions across groups or settings that affect the 

absolute effectiveness of the option or the importance of the problem for 

disadvantaged groups or settings?

− Are there important considerations that should be made when implementing the 

intervention (option) in order to ensure that inequities are reduced, if possible, and 

that they are not increased?

For equity, no research evidence was identified. However, the WG expressed concern for 

possible inequity, noting that under-served populations may have difficulty accessing and 

paying for the vaccine. WG members noted that travelers visiting friends and relatives (VFR)

travelers in cholera endemic areas are likely at highest risk for illness, but are often uninsured.

For other travel vaccines, VFR travelers are often less likely than other travelers to go to travel 

clinics and receive pre-travel vaccines. The WG determination for equity was that “Varies.”

The primary question and sub-questions identified by the WG to assess feasibility included the 

following:

 Is CVD 103-HgR feasible to implement among children and adolescents aged 2-17 years 

traveling to an area with active cholera transmission?

− Is the intervention sustainable?

− Are there important barriers that are likely to limit the feasibility of implementing the 

intervention or that require consideration when implementing it?

− Is access to the vaccine an important concern?

− Would the vaccine recommendation have any impact on health equity?
ACIP Meeting Summary January 12, 2022

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− Are there important considerations when implementing the intervention in order to 

ensure that inequities are reduced, if possible, and that they are not increased?

The WG felt it is likely feasible to administer the vaccine to children and adolescents aged 2-17 

years in a travel clinic. The travel clinic study is preferred because the dose preparation is more 

complicated than routine childhood vaccines. It requires reconstitution in bottled or purified 

spring water and half the buffer is discarded for children aged less than 6 years of age. 

Additionally, it may be optimally ingested with specific sweeteners. More than 92% of trial 

participants used PureVia Stevia with their dose and 89% of study participants consumed the 

complete vaccine dose. Seroconversion with partial dosing was encouraging. The 69% of 

participants who consumed less than 50% of the dose and all 7 patients who consumed 50% to 

80% of the dose seroconverted. Finally, the recommendation may impact health equity as 

previously discussed. The WG determination for feasibility was “Probably yes.” 

This table summarizes the WG’s determinations for each of the EtR domains just discussed: 

Based on the EtR Framework, the WG considered the balance of consequences and their 

consensus was that the “desirable consequences probably outweigh undesirable consequences 

in most settings,” given that they had only indirect data to assess the desirable consequences.

Finally, the WG consensus was that the type of recommendation should be, “We recommend 

the intervention CVD 103-HgR for children and adolescents aged 2-17 years traveling

to an area with active cholera transmissions.” 

Discussion Summary

Dr. Poehling noted that at one point, there was mention about how individuals would choose 

whether to get the vaccine because it is an individual benefit. However, the conclusion was that 

it should be recommended and there was a choice for shared decision-making. She requested 

further elaboration to help her better understand the conversations on those 2 choices. 

Dr. Collins indicated that the WG spent a long time deliberating how they wanted to rate the

specific domain of “public health problem.” Some of that is because the EtR Framework was 

created with the lens of more general vaccines and policies of routine immunization in mind. 

Travel vaccines are thought of somewhat differently. Overall, the WG felt that they wanted to 
ACIP Meeting Summary January 12, 2022

12

recommend the vaccine, but also acknowledged that some people may feel that it does not 

meet the criteria for being a public health problem in the US. Individual travelers may be at risk 

and the status of people’s individual risk factors (e.g., heart disease, Blood Type O, low gastric 

acids, partial gastrectomy, other factors) that may increase their potential for experiencing 

cholera gravis may be unknown. While WG members agreed on recommending vaccine for 

travelers to endemic areas, they debated extensively whether this meets the criterion of being a 

public health problem. The proposed language for consideration is a full recommendation for 

adults aged 18-64 years who are traveling to areas of active cholera transmission.

Ms. Bahta recalled that some of the cholera cases that occurred in the US during 2012-2018 

were not travel-associated and requested additional information about whether these were 

secondary infections acquired from other people who had traveled. In addition, she requested 

further information about the mention that cholera could become a bigger problem in the future.

Referring to Slide 9, Dr. Collins noted that 64 cholera cases were reported during that 6-year 

period. Of those, 88% of those were travel-associated. Typically in this surveillance system, 

they see that other cases were associated with Gulf Coast seafood consumption or swimming

in Gulf Coast waters where Vibrio cholerae is endemic. Occasionally through surveillance, cases 

are identified without a particular cause identified. However, she suspects the others were 

associated with Gulf Coast waters as well. In terms of the potential for becoming a bigger 

problem in the future, cholera had not occurred in Haiti for a very long period of time until the 

hurricane in the early 2000s after which there was epidemic cholera in Haiti. Most travelers to 

the US currently do not travel to cholera endemic areas, but Vibrio cholerae has a reservoir. 

Therefore, it can be hard to predict what areas might become unsafe cholera risk areas over 

time. It is important to remember that cholera is under-reported in the US and globally.

Dr. Bell requested further information about whether there have been any rare SAEs noted and

if so, in general what the reports look like with this vaccine once the vaccine has been used. 

Referring to Slide 68, Dr. Collins indicated that they had their colleagues in the Immunization 

Safety Office (ISO) retrieve data from when the vaccine was approved in 2016 through February

2021. These data were generated using the Bayesian mining process. The only events

identified that occurred more commonly with Vaxchora® than with other vaccines related to the 

fact that this is an oral vaccine that requires people to not eat close to ingestion. People may 

have consumed food in closer proximity than was recommended. The product administered to 

patients of an inappropriate age may have been one issue for patients less than 18 years, and 

theoretically could be an issue for patients ≥65 years of age. That is, some of these seem to be 

related to administration and not SAEs. Preparation and administration are complicated, which 

drove part of the WG’s discussion about recommending that the vaccine be administered in a 

travel clinic.

Dr. Sanchez added that clearly, the intent is that this administration of this vaccine in a travel 

clinic is anticipated to facilitate inherent issues with administration. The WG debated whether 

this is a public health problem because there are so few cases in the US. However, it may be a 

public health problem for individuals who are traveling to cholera endemic areas depending 

upon the lifestyles they choose in those areas. He would prefer to a recommendation rather

than shared decision-making because of the AEs of cholera.

Dr. Loehr inquired as to whether Dr. Barnett from the International Society for Travel Medicine

(ISTM) could comment on whether ISTM has an opinion.
ACIP Meeting Summary January 12, 2022

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Dr. Barnett (ISTM) reported that while she did not think it would be used in a travel medicine 

situation for all traveling children, members of the ISTM would be happy to have this vaccine 

available to eligible children who will be in an outbreak or other situation in which they may be 

exposed to cholera. 

Dr. Brooks asked how many doses per year of vaccine are utilized currently for individuals ≥18

years of age. Dr. Collins did not have the number of doses administered annually on hand, but 

indicated that he would try to find out and would circle back to ACIP with that information.

Dr. Grogg (AOA), also an ISTM member, pointed out that many travel medicine clinics have 

closed because of COVID-19 and the limited supply of Yellow Fever (UF) vaccine. As a 

pediatrician, he said he was in favor of having a pediatric vaccine and would recommend that 

the vaccine be available, but the recommendation about administration at a travel medicine 

clinic may be a barrier. 

Dr. Lee thought the context of a recommendation for those who are going to endemic areas 

made a lot of sense and felt that the shared clinical decision-making was for when the benefitrisk balance to an individual is uncertain. In this case, what is uncertain is the risk based

on where someone travels and what is/is not known about the prevalence of cholera in those 

areas. For those traveling into a high-risk area, it seems like a straightforward recommendation 

would be worthwhile given what was presented about the benefit-risk balance. Additional clinical 

considerations or clinical guidance from CDC or ISTM to help clinicians understand the actual 

risk would be beneficial. She also asked about the durability of immunity, when revaccination

would be recommended, and if that information would that be provided in the clinical guidance 

or in other areas. 

Dr. Collins indicated that there would be a clinical considerations presentation during the next 

meeting prior to any votes. There are no data available about safety or efficacy in preventing 

cholera with boosters for the current formulation. Little is known about the duration of protection 

beyond the 3-month period that was evaluated in the oral challenge study in adults aged 18-45 

years. ACIP does not currently have a recommendation for adults regarding the use of booster 

doses and is unlikely to make such a recommendation for children given the limited data.

Dr. Lee emphasized that it would be helpful if there is an opportunity to collect at least 

immunogenicity data in terms of long-term follow-up.

Dr. Sanchez emphasized that endemic cholera is not reported in many of the developing 

countries and a lot of cholera outbreaks occurring in endemic countries are not being reported 

to the World Health Organization (WHO), so they are likely seeing only the “tip of the iceberg.” 

Therefore, this vaccine will be important as a contributor to travel medicine vaccines. 

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 US, there are no existing 

ACIP TBE vaccine recommendations. The TBE Vaccine WG was formed in September 2020 to 
ACIP Meeting Summary January 12, 2022

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review the use of TBE vaccines in US persons traveling abroad and laboratory workers. The 

TBE Vaccine WG’s Terms of Reference (TOR) are to: 1) review information on TBE, including 

its epidemiology, clinical presentation, diagnosis, treatment, and outcome; 2) review data on

infection risk and burden for travelers and laboratory workers; 3) review data on vaccine safety, 

immunogenicity, and effectiveness; 4) provide evidence-based recommendation options for 

ACIP; 5) identify areas in need of further research for informing potential future vaccine 

recommendations; and 6) publish ACIP recommendations in the Morbidity and Mortality Weekly 

Report (MMWR). 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 civilian US 

travelers, laboratory workers, and US military personnel. In September 2021, the WG presented 

the immunogenicity and safety of Pfizer’s TBE vaccine. The focus of the January 12, 2022 

session was on follow-up of ACIP member questions regarding the immunogenicity of 1 or 2 

doses of TBE vaccine, the EtR Framework for TBE vaccine for persons who travel abroad and 

laboratory workers. The plan is to be prepared to have an ACIP vote on vaccine 

recommendations and finalize the MMWR in February 2022 before the next tick season.

Immunogenicity of 1 or 2 Doses of TBE Vaccine

Dr. Susan Hills (CDC/NCEZID) presented some data to follow up on ACIP member questions

from the September ACIP meeting. During that meeting, several members commented on the 

challenges of the TBE vaccine schedule in terms of travelers having sufficient time to finish the 

primary series of vaccine before travel, given that a minimum of 5 to 6 months are needed to 

complete the 3-dose primary series. The WG discussed this issue and agreed with this concern. 

In terms of the seropositivity rates following each of the doses in the primary series in adults, 

one study2 showed that after only 1 dose of vaccine right before the second dose was given at 

12 days, the seropositivity rates were 52% percent for younger subjects aged 16-49 years and 

27% for older subjects aged 50-79 years. Once Dose 2 was administered, seropositivity rates 

measured 3 weeks later had increased to 97% in the younger age group and 88% in the older 

age group. Subsequently, at 3 months and 5 months after Dose 2, seropositivity rates had 

dropped to 71% to 79% for the younger age group and 61% to 65% for the older age group. 

After Dose 3 was given, seropositivity rates measured 3 weeks later had increased to 99% to 

100% in both age groups. While there is no formal TBE correlate of protection, a neutralizing 

antibody titer of ≥10 is commonly considered to be a surrogate marker of protection. Similar to 

the seropositivity results, geometric mean titer (GMT) data from the same study were higher in 

the younger adults compared to older adults. In both groups at 3 weeks after Dose 2, GMTs 

were moderate. At 3 months and 5 months after Dose 2, the GMTs had dropped and were close 

to the seropositivity cutoff of 10. When Dose 3 was given, there was a robust response with a 9- 

to 15-fold increase in GMTs. 

Data from a study3 with children aged 1-11 years with data at 1 and 5 months after Dose 2 and 

1 month after Dose 3 show that seropositivity rates decreased only slightly from 100% at 1 

month after Dose 2 to 95% at 5 months after Dose 2. Similar to the adult results, the GMTs 

decreased notably during the same period from 237 initially to only 40 at 5 months after Dose 2. 

When the third dose was given, the GMTs increased more than 13-fold. Other studies had 

similar patterns.

2

 Loew-Baselli A et al. Vaccine 2011;29:7307-19/FDA Memo 3

 Pollabauer EM et al. Vaccine 2010;28:4680-5; Prymula R et al. Hum Vaccin Immunother 2012;8:736-42 
ACIP Meeting Summary January 12, 2022

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In summary, after only 1 dose of TBE vaccine, seropositivity rates and GMTs are low. This 

suggests 1 dose is unlikely to provide much protection for a traveler. After the second dose, 

seropositivity rates and GMTs initially increase then decrease in the following months. There is 

clear variability in the response by age group, with lower rates and GMTs in older adults. While 

there is no correlate of protection for TBE, it is concerning that GMTs are close to the 

seropositivity cutoff within a few months of the second dose. Administering the third dose of the 

primary series results in an increase in seropositivity rates and a notable boost in the GMTs,

often with a 10-fold or higher increase in GMTs. After considering and discussing these data 

and findings, the WG concluded that it is important to recommend that a 3-dose primary series 

be completed prior to a traveler’s departure in line with the Food and Drug Administration 

(FDA)-approved schedule if at all possible. However, the results from studies on 

immunogenicity after only 1 or 2 doses will be included in the MMWR documents to allow 

healthcare providers (HCP) to counsel individual travelers if they are not able to complete the 

full series prior to travel.

EtR Framework for Travelers & Laboratory Workers

Dr. Susan Hills (CDC/NCEZID) next provided a very brief reminder of the key information on 

TBE and TBE vaccine and discussed the evidence the WG considered in drafting the TBE 

vaccine recommendations. TBE is a flavivirus related to Powassan virus. There are 3 main 

subtypes of TBE virus (European, Siberian, and Far Eastern) 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.4 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 locally 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.5

The main risk period occurs in the warmer months from April through November when ticks are 

most active.6 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 invasive disease occurs, it can have 

potentially high fatality rates of 1% to 20% and high sequela rates of 10% to 50%.

The TBE vaccine manufactured by Pfizer as TicoVacTM was approved by the FDA in 2021 for 

use in persons ≥1 year of age. Although only recently licensed in the US, the current adult

formulation (0.5 mL) for persons aged 16 years and above and pediatric formulation (0.25 mL) 

for children and adolescents up to 15 years of age have 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.

Now turning to the EtR framework and the WG’s key considerations for development of draft 

recommendations for persons who travel abroad. The policy question was, “Should TBE 

vaccine be recommended for use in persons aged ≥1 year traveling to or residing in TBE risk 

areas?” The first domain of the EtR the WG addressed was the question, “Is TBE of public 

health importance?” For this domain, 5 key factors were considered. The first regarded whether 

is of public health importance for residents of some TBE endemic countries. For example, the 

median incidence of reported TBE cases in European countries that reported data in 2019 was 

4 https://www.ecdc.europa.eu/en/tick-borne-encephalitis 5

 Dobler et al, Wien Med Wochenschr 2012 

6

 Source: https://www.ecdc.europa.eu/en/publications-data/epidemiological-situation-tick-borne-encephalitis-european-union-andeuropean 
ACIP Meeting Summary January 12, 2022

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1.3 per 100,000 population. Second, TBE cannot be considered an important public health 

problem overall for US persons traveling to risk areas. With a median of 1 diagnosed case per 

year among millions of travelers to TBE endemic countries, the estimated risk of TBE is less

than 1 case per million trips. However, TBE is an important concern for certain subpopulations 

of travelers who have itineraries/activities that put them at higher likelihood of receiving a tick 

bite, or because they plan to live in or travel recurrently to risk areas. TBE can be a very severe 

disease with variable but potentially high case fatality and sequelae rates and there are no 

specific antiviral treatments. TBE is more an individual rather than a societal concern. TBE 

vaccine will be paid for out-of-pocket by most civilian travelers, given that travel vaccines are 

generally not covered by insurance. TBE vaccine will not be covered under the Vaccines

for Children Program (VFC). Therefore, the individual traveler will bear both the cost and the 

benefits of vaccination. The WG’s conclusion on public health importance was that it “varies. For 

the US traveling population overall, TBE is not a problem of public health importance. However, 

it is a concern for certain individuals who are at a higher risk of a severe disease, which can 

result in death or permanent sequelae.

For the second domain of benefits and harms the WG considered the results based on the 

GRADE assessments and the following questions:

 How substantial are the desirable anticipated effects?

 How substantial are the undesirable anticipated effects?

 Do the desirable effects outweigh the undesirable effects?

The outcomes the WG aimed to assess included protection from disease after the 3-dose 

primary series, and after a booster dose at 3 years after the primary series. However, there are 

no efficacy data for TBE vaccine and low TBE incidence would make such trials infeasible. In 

the absence of efficacy data, the WG reviewed immunogenicity data that noted 2 limitations. 

While a neutralizing antibody titer of ≥10 is typically used to indicate seropositivity, there is no 

established immunologic correlate of protection to TBE. Second, the vaccine is based on a 

European subtype TBE virus, which is 1 of the 3 main TBE virus subtypes and likely has crossprotection against the other 2 TBE virus subtypes transmitted in the Eastern part of the TBE 

endemic region. The supporting data are limited. To assess initial seropositivity after the primary 

series, data were identified from 10 studies (7 adult, 3 pediatric). All were observational studies.

At 1 month after the primary series, seropositivity rates were 96% or higher in all but 1 study. 

When subjects in 1 of the adults and 1 of the pediatric studies were followed up at 3 years after 

the primary series, which is immediately prior to the booster dose, seropositivity rates remained 

high at 94%. To assess seropositivity after the booster dose, there were 2 studies (1 adult, 1 

children). They all were observational studies. At 1 month after the booster dose, seropositivity 

rates were 100%. At 5 years, they were 94% or higher and at 10 years, seropositivity rates were 

85% or higher. Based on these data, the WG considered the desirable anticipated effects to be 

large.

In terms of how substantial the undesirable anticipated effects are, the WG reviewed data on 

SAEs. In 4 RCTs and 9 observational studies among almost 7,000 adult and pediatric subjects 

who received at least 1 dose of vaccine in the primary series, there were no vaccine-related 

SAEs reported. In 3 active post-marketing surveillance studies among almost 2,700 adults and 

children, there was 1 vaccine-related SAE of a febrile convulsion in a child. The possible 

contributing factors included rhinopharyngitis, gastroenteritis, and otitis media. Based on these 

data, the WG considered the undesirable anticipated effects to be “minimal.”
ACIP Meeting Summary January 12, 2022

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Regarding whether the desirable effects outweigh the undesirable effects, the WG noted that 

there were high seropositivity rates and no serious safety concerns, and that vaccination can 

prevent a rare but potentially serious and untreatable disease. However, the WG also noted that 

HCP should discuss the balance of desirable and undesirable effects with individual travelers 

based on their itinerary and activities. As with any vaccine, rare SAEs can occur. For some 

travelers, even a low probability of an SAE might be higher than their disease risk. Therefore, 

vaccination should be targeted to travelers at higher risk for disease. Overall, the WG 

determined that if the vaccine is used in line with the proposed recommendations, the balance 

of desirable and undesirable effects “favors the intervention.”

The GRADE assessment results were used to determine the overall certainty of the evidence 

for the critical outcomes. For protection from TBE, the overall certainty of the evidence was 3 

(Low). Certainty was downgraded based on results being from observational studies only, and 

for indirectness because there were no efficacy data. The likelihood of protection from disease 

was based on seropositivity with no established correlate of protection and there is unconfirmed 

cross-protection against non-European TBE virus subtype. Certainty was upgraded because of 

the magnitude of effect. For SAEs, the overall certainty of the evidence was “moderate.” Some 

data were available from RCTs, but evidence was downgraded because of the risk of bias from 

inadequate blinding.

For the domain of values, 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?

For this domain, 3 studies informed the WG’s response. The first study7 investigated TBE 

vaccination practices of non-US adults who had traveled to a TBE endemic country. This 

included travelers from Canada, Germany, Sweden, and the United Kingdom (UK). Among 365 

travelers who had engaged in an activity that put them at higher risk of TBE, only 15% had 

received a vaccine before their trip. The most frequent reason given for lack of vaccination was 

a perception of insufficient risk. These results suggested that even in a higher risk setting, 

travelers had variable attitudes toward the value of vaccination. A second publication8

investigated TBE vaccination rates among residents of Sweden where TBE is endemic and TBE 

vaccine must be paid for out-of-pocket. TBE vaccination rates were 33% in residents of risk 

areas and 18% in other areas. This again suggests variable attitudes toward vaccination, even 

in the context of ongoing risk. The WG reviewed 1 publication of US population perceptions of 

vaccinations when considering Japanese encephalitis (JE).9 The WG considered this study 

because there are many similarities between JE and TBE and JE vaccine and TBE vaccine. 

These include that the disease risk for travelers is very low, the potential impact of disease is 

high, both vaccines are safe and effective, and both vaccines are high cost at over $250 per 

dose. When participants were presented with information describing the low risk of JE but the 

potentially high consequences of disease, the vaccine immunogenicity and safety, and 

information on the vaccines cost, the responses from the almost 6,500 participants indicated 

7 Marano C et al. Perceptions of tick-borne encephalitis risk: a survey of travelers and travel clinics from Canada, Germany, Sweden 

and the UK. J Travel Med 2019;26(Suppl 1):S10–S16 8 Slunge D. The willingness to pay for vaccination against tick-borne encephalitis and implications for public health policy: Evidence 

from Sweden. PLoS One 2015;10:e0143875 9 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;38:2117–21
ACIP Meeting Summary January 12, 2022

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43% were very or somewhat unlikely to be vaccinated, 25% were unsure, and only 32% were 

very or somewhat likely to be vaccinated. When noting factors important in their decision, some 

valued the availability of vaccine to prevent a disease with potentially serious outcomes and no 

specific treatment. Others were less likely to value an expensive vaccine with the possibility of 

rare serious side effects. Based on these findings, the WG determined that it is likely the US 

traveler population will have variable opinions on whether the desirable effects of vaccination 

are large relative to undesirable effects. The WG similarly determined that there likely will be 

important uncertainty or variability in how much people value the vaccine.

Regarding the domain of acceptability of TBE vaccine, no formal evaluation of acceptability was 

undertaken. However, the WG discussed acceptability for the groups considered to be the key 

stakeholders, including US travel medicine and other HCP providers. The WG considered that 

TBE vaccine is likely to be acceptable to US HCP based on the attitudes and practices of 

European healthcare providers. TBE vaccine has been available in Europe for decades and is 

actively recommended by European HCP for higher risk travelers to endemic areas. For the 

public, TBE vaccine recommendations are expected to be acceptable because vaccine 

availability gives an option, in addition to tick bite prevention measures, for protection from a 

potentially severe disease. The WG therefore thought the intervention would be acceptable to 

key stakeholders.

For the domain of resource used, the WG considered whether TBE vaccination is a reasonable 

and efficient allocation of resources. A cost-effective analysis for TBE vaccination of travelers 

has not been conducted. Most travel vaccines are not cost-effective. TBE vaccines for travelers 

are not likely to be cost-effective because the number of US travelers needed to be vaccinated 

to prevent 1 case is very high. However, the WG noted that cost-effectiveness considerations 

are less relevant for a travel vaccine when the decision on vaccination is for an individual 

traveler and not being made for the population as a whole, when vaccine is typically paid

for by the traveler themselves and is generally not paid for by insurance, and when the vaccine 

is not covered under the VFC Program. Cost-effectiveness analyses have been conducted in 

some endemic areas, but the results have been variable. Programs are often not projected to be 

cost-effective, with incidence and vaccine cost being important variables in predicting costeffectiveness. The WG also considered resource allocation issues. Vaccine recommendations 

targeted to higher risk groups are probably an efficient use of resources, as the financial 

implications of vaccine purchase will be borne by travelers most at risk of a severe disease who 

will, therefore, receive the most benefit. However, even among higher risk travelers, there will 

be variability in whether vaccine purchase is a reasonable allocation of resources based on 

several factors, including the actual risk of disease, the likelihood of use of other tick prevention 

measures, and opportunity costs such as buying TBE vaccine versus purchasing travel 

insurance or other vaccines with available financial resources. The WG also considered under 

this domain that healthcare costs for management of TBE presenting as neurologic illness are 

potentially large. Based on these factors, the WG determined that whether TBE vaccination is a

reasonable and efficient allocation of resources “varies” depending on the individual traveler. 

With respect to the d of equity, TBE vaccine will cost more than $750 for a primary series and 

will be paid for out-of-pocket by most travelers or by insurers or employers in some cases. 

Currently, the approach to TBE prevention for US travelers is tick bite prevention measures. 

Vaccine available would lead to health disparities because some travelers will have the 

resources to pay for the vaccine or have it paid for and others will not. However, the absolute 

risk of TBE is low and only a small number of travelers will require vaccinations. Overall, 

vaccine availability will not cause substantial population disparities. Additionally, the WG noted 
ACIP Meeting Summary January 12, 2022

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that TBE vaccination recommendations cannot address this issue. The WG’s conclusion was 

that the impact on health equity would be “probably reduced” by TBE vaccine availability.

For the domain feasibility, the WG considered whether implementation of TBE vaccination is 

feasible to implement. While the WG felt that administration of TBE vaccine would be feasible 

as part of a pre-travel consultation, they felt the key barriers to implementation would be that the 

primary vaccination schedule requires a minimum of 5 months to complete. Secondly, they felt 

that many travelers to TBE endemic countries, particularly Europe, are unlikely to consult am 

HCP before travel or to consult with a non-specialist HCP. There might be a lack of provider 

understanding about which travelers are at highest risk for TBE and might benefit most from 

vaccination. To address this, CDC will be posting resources on its website once 

recommendations are approved. The decision overall was that the intervention is “probably 

feasible” to implement.

Overall, when considering all the domains of the EtR Framework, the WG determined that the 

“desirable consequences probably outweigh the undesirable consequences in most settings.” 

Policy option category the WG would opted to propose was that “TBE vaccination for persons 

who travel abroad should be based on shared clinical decision-making.” The WG’s draft 

recommendations for ACIP consideration is:

TBE vaccine should be considered for persons aged ≥1 year traveling or moving abroad 

to TBE endemic areas if they are at risk of TBE virus exposure through engaging in 

outdoor activities during the transmission season in environments where ticks are likely 

to be present.

The recommendations will be accompanied by additional information to ensure that HCP can 

have informed discussions with travelers about TBE vaccine and disease prevention. This will 

include information on factors that increase the risk of infection, including a table with detailed 

information on risk factors for TBE virus exposure; the need for all travelers to take precautions 

to avoid tick bites; advice to avoid consumption of unpasteurized dairy products; and information 

on general factors to consider in the decision whether to vaccinate, such as the likelihood of 

future travel to TBE endemic areas and the rare occurrence of TBE at its potentially high 

morbidity and mortality.

Regarding the EtR Framework for TBE vaccine use among laboratory workers, TBE virus 

transmission occurred through virus aerosolization either during laboratory procedures or 

handling of infected animal waste. Transmission through accidental percutaneous or mucosal 

exposures is possible. At least 46 laboratory-acquired TBE virus infections were reported 

globally prior to 1995. Among these, at least 4 occurred among US laboratory workers—all 

before 1979. Currently, fewer than 10 laboratories in the US work with TBE virus for diagnostic 

or research purposes. Although research activity might increase with the availability of a 

vaccine.

The policy question the WG considered was, “Should TBE vaccine be recommended for use in 

laboratory staff working with TBE virus?” The population for vaccination was considered to be 

persons working with TBE virus for diagnostic or research purposes and having a scientific 

understanding of disease and vaccines. The same GRADE assessment for outcomes of 

vaccination was used as was used for travelers. For the first domain regarding whether TBE is a 

public health problem, TBE cannot be considered of public health importance overall, given that 

only 4 cases of laboratory-acquired infection have ever been reported in the US. However, for 

laboratorians working with TBE virus, there is a risk of a severe disease that can result in death
ACIP Meeting Summary January 12, 2022

20

or permanent sequalae.

For values, the WG considered that scientists are likely to consider the desirable effects to be 

large relative to the undesirable effects since they will understand the risks of disease and risks 

and benefits of vaccination. The WG did not think that there is likely to be important variability 

among scientists. TBE is likely to be accessible to key stakeholders, including occupational 

health directors, laboratory workers, and other researchers because its availability will improve 

safety and remove a barrier to research.

For the domain of resource use, the WG felt that TBE vaccination was a reasonable allocation 

of resources because there are only a limited number of staff working with TBE virus and 

vaccination is a small cost to pay to avoid the potentially serious impact of a worker becoming 

infected. The WG thought that equity probably would be increased as TBE vaccine will likely be 

paid for by employers and will improve safety for staff at occupational risk of a severe disease. 

The WG also thought that vaccination would be feasible to implement as it will likely build on 

existing occupational health programs for laboratory workers.

Overall, when considering all of the domains of the EtR Framework, the WG determined

that the desirable consequences of TBE vaccinations for laboratory workers clearly outweigh 

the undesirable consequences in most settings. The policy option category the WG proposed 

was is that TBE vaccination is “recommended” for laboratory workers. The draft 

recommendation for ACIP members’ consideration is:

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

TBE virus.

The recommendations will be presented with additional text to provide clear information for 

implementation, including noting that a local institutional biosafety committee should undertake 

a risk assessment of the potential for exposure to TBE virus, considering the type of work to be 

performed and the biosafety level at which work is being conducted. The vaccination is not 

required for workers handling routine clinical samples.

In terms of next steps, the WG anticipates asking ACIP members to vote on the TBE vaccine 

recommendations during the February 2022 ACIP meeting prior to the next TBE virus 

transmission season. Following the meeting, the MMWR documents will be finalized and 

published.

Discussion Summary

Dr. Lee asked with 20 years and 75 million doses administered whether there are any postmarketing efficacy or safety data available from other countries that could help inform ACIP’s 

decision-making and augment the clinical trial data.

Dr. Hills indicated that there are some VE data, but none are directly relevant to the Pfizer 

vaccine. There are 2 vaccines available in Europe, one of which is the Pfizer vaccine. Some of 

the VE data from studies conducted in areas where there is availability of both vaccines are not 

directly relevant to the Pfizer vaccine. In Austria, 85% to 95% of vaccine use was of the Pfizer 

vaccine. When the VE study was conducted, VE was higher than 90%. The WG reviewed and 

discussed those data and were reassured about the high VE. In addition to the limitation of 

there being 2 vaccines, the schedule used in Austria was slightly different. In terms of safety 

data, over 75 million doses have been administered over a period of 20 years. While there is no 
ACIP Meeting Summary January 12, 2022

21

formal publication, the manufacturer has a safety database that ACIP has seen. However, a 

limitation is that data reported to the manufacturer are more likely to be those in which an AE or 

SAE has occurred. CDC has reached out to colleagues in Europe several times to ask if they 

have any national-level reports or local publications available to which CDC could access. It has 

not been possible to obtain any additional data from them to date, primarily because they have 

been actively involved in the COVID-19 response, but they have responded that there is 

confidence that it is a safe and effective vaccine.

Taking a step back from TBE in particular, Dr. Lee suggested considering a process for how to 

incorporate data for well-established vaccines into the EtR Framework to assist ACIP with the 

decision-making process. She reminded everyone that she expressed her opinion previously 

about shared clinical decision-making versus a recommendation for use. Speaking only for the 

travel vaccines, she requested that her fellow committee members provide their perspectives on 

the use of shared decision-making in the context of travel vaccines and when that seems 

appropriate. Her feeling at this point was that if the benefit/risk balance made sense and highrisk situations could be reasonably defined, it should be a recommendation.

Dr. Poehling reported that the WG had a robust discussion about this and there were pros and 

cons in all directions. The thought process that led the WG to the draft recommendation was 

that TBE vaccine is relatively similar to the JE vaccine in that it is recommended for few 

persons, which is an individual benefit. With that in mind, the thinking was that this would 

involve shared decision-making. She called upon WG member Dr. Chen, who is a travel 

medicine specialist, to elaborate further.

Dr. Chen said he had gone back and forth trying to interpret and understand the shared 

decision-making model versus a recommendation. While he would rather have a unified 

approach, the WG discussed the variability of risk and how to clearly define that. That is the role 

of the travel clinic consultation. Although limited data were available, the WG had confidence in 

the safety of the vaccine and a reasonable belief that it has good efficacy. It is a question of how 

this recommendation is framed. Is it from the context of a population-wide recommendation in 

that the population would obtain benefit versus the individual? Many segments of the population

that are not traveling and certainly would not receive any benefit. There is a wider context in 

which many travel vaccines for endemic diseases exist in other countries. The WG has gone 

back and forth trying to understand, but Dr. Chen thought it would be helpful to address this 

again in a unified fashion.

Dr. Sanchez agreed that although an individual may have a choice with respect to receiving the 

vaccine or not, it seemed that ACIP should make a firm recommendation that individuals should 

receive the vaccine under certain circumstances that pose high risk rather than having shared 

decision-making. It is always up to the individual to decide whether to receive a vaccine. Given 

the evidence available and what is being done in countries where TBE is endemic, he thought 

people deserved a formal recommendation from the ACIP. He asked whether countries such as 

Austria and others that are administering this vaccine have formal recommendations that the 

entire population should get it and what age they are receiving TBE vaccine.

Dr. Hills indicated that there is substantial variability in recommendations in Europe for TBE 

vaccine use and for whom the vaccine is recommended. When there are recommendations, 

they are variable from country-to-country. Approximately 50% of countries with endemic TBE 

have recommendations. Austria has a recommendation for the entire population but is the only 

country with a national recommendation. Germany has a recommendation for vaccination
ACIP Meeting Summary January 12, 2022

22

for persons who live in higher-risk areas in the country, and they define those higher-risk areas. 

Some countries have a recommendation only for those who are occupationally exposed, while 

other countries have a recommendation only for those who are going to be undertaking 

extensive outdoor activities. Recommendations for entire populations are rare. Vaccination 

recommendations are made in Austria beginning with young children ≥1 year of age. Germany 

also has a recommendation that begins with young children. Recommendations would be only 

for adults in countries that recommend the vaccine only for those at occupational risk. Uptake in 

Austria is over 80%. In other countries, uptake is typically low at about 25%. There is variability 

in uptake not only due to personal choice, but also because it is not reimbursed in most places 

and people would have to pay out-of-pocket.

Dr. Brooks recalled that the vaccine is a 3-dose series with a booster and requested further 

information on duration of protection and when the booster would be needed.

Dr. Hills indicated that following the 3-dose primary series, seropositivity remains high for 

several years at very good rates. The booster is recommended 3 years after the primary series. 

After the booster dose is given, seropositivity remains very good for at least 10 years. Again, 

there is no correlate of protection.

Dr. Kotton noted that she has engaged in a fair amount of travel medicine, predominantly in 

immunocompromised patients. She was struck by the overall paucity of cases, with only 11 

cases in 20 years in civilian travelers and 9 cases in military personnel over a 14-year period. 

Therefore, her preference would be shared clinical decision-making rather than an official 

recommendation. While it seemed rare that the vaccine would be warranted and would not be 

routinely given, she would be happy to have it available for cases in which she feels a patient 

may be at risk.

Dr. Long thought they were confusing what shared decision-making might entail in this regard. 

She thinks of shared decision-making in cases when there is a potential difference in how an 

individual values the vaccine or values having protection. In this situation, the only decisionmaking would be the level of someone’s risk. That might be very difficult to define on a 

population basis, but not too difficult to define on an individual basis in terms of degree and 

length of exposure in areas where the virus is endemic. There should be a clear 

recommendation that those at highest risk should be vaccinated. The difficulty will be in 

differentiating individuals or making rules that would define high-risk and length of exposure. 

She thinks of that as individual value rather than shared decision-making and would prefer to 

make a recommendation that does not result in variability in use of the vaccine.

Dr. Lee agreed with the statement about distinguishing between risk-based recommendations

and shared clinical decision-making recommendations.

Dr. Virginia Caine asked whether it is known that at 10 years, GMTs are sufficient for protection 

or just that there is antibody and lack of clarity about the level of protection.

Dr. Hills indicated that the GMTs were assessed for up to 3 years after the primary series and 

up to 10 years after the booster dose. Given that there is no formal correlative protection for 

TBE, it cannot be said definitively that somebody with a particular neutralizing antibody titer is

definitely protected. There are no VE data, but it is assumed that a GMT of ≥10 equates with 

protection. Laboratory workers would be recommended to complete the primary series and 

consider a booster dose. There may be consideration of potential additional doses for laboratory 

workers who are working with live TBE virus and have neutralizing antibody titers <10. There 
ACIP Meeting Summary January 12, 2022

23

will be additional information for laboratory workers indicating that a local biosafety committee 

should be involved in considering the level of risk for laboratory workers depending upon the 

activities they are undertaking. That is considered to be a critical part of consideration for 

vaccine recommendations for laboratory workers.

Dr. Baker (IDSA) noted that some viral vaccines that are recommended as a 3-dose primary 

series. Given the data shown on serology after the second dose, she wondered whether any 

data were available on someone who has received 2 doses and were then exposed whether in 

terms of whether that might prevent disease. Knowing that there is no correlate of protection, 

she asked whether there is any hint that if someone has a reasonable GMT after 2 doses they 

might be protected based on serology. In addition, she asked if/how insurance might be 

impacted with shared decision-making versus recommendation.

Dr. Hills indicated that there are some VE data, but not specifically for the Pfizer vaccine given 

the availability of more than 1 vaccine in Europe. While there are no data to look closer at what 

the considerations might be, it is known that seropositivity rates are variable by age. Older 

persons do not have seropositivity rates or neutralizing antibody titers as high as younger 

people, so age would be one factor to consider. Another factor would be the time point after the 

second dose (e.g., 1 month, 5 to 6 months, et cetera). It is somewhat nuanced, but there are no 

data to answer this definitively. It is known that people who receive 2 doses who may be 

traveling during the subsequent TBE virus transmission season likely would have seropositivity. 

Given the various nuances in terms of age, how long somebody may be traveling, and that their 

neutralizing antibody titers might decrease over time, the WG was not willing to make a 

recommendation for just 2 doses for travelers. However, this type of information will be provided 

so that HCP can refer to that when counseling travelers.

Dr. Lee pointed out that other issues that are relevant to travel vaccines are equity, access, and 

affordability. Recognizing how the current system is, ACIP should not be asking individuals for 

any particular disease to have out-of-pocket costs if they are at high risk for that illness or are 

hospitalized upon return from travel. While this is a basic issue that cannot be fixed through 

recommendations, ACIP should recognize that equity, access, and affordability are driving 

issues that likely would contribute to shared clinical decision-making around the use of TBE 

vaccine. While they do not want cost to be a factor in someone’s decision, practically it could be. 

This particular category is challenging because it means different things to different people. Her 

hope was to use a consistent approach to thinking about the framework for when the vaccine is 

appropriate to use and advocating for something that clarifies whether there is a benefit. In the 

case of a high risk of vaccine AEs or perhaps inconsistent or incomplete effectiveness, she 

does believe it would be appropriate recommend shared clinical decision-making. However, 

ACIP should be consistent with its risk-based recommendations from the past for routine and 

travel vaccines.

Dr. Barnett (ISTM) asked whether there are now or will be data about shortened dosing intervals

for last-minute travelers and observed that this vaccine differs somewhat from other travel 

vaccines. Travelers to Europe do not typically go to travel clinics for preparation. Therefore, 

perhaps a wider range of providers should be asked for advice about this vaccine. She agreed 

with all who said that the recommendations will need to be very clear and specific about who 

would be at greatest risk and would need this vaccine. The JE vaccine recommendations were 

written with that in mind, but that vaccine is given primarily in travel clinics. ACIP needs to 

wrestle with the issue of whether 2 doses would be sufficient for a traveler who is leaving in 6 

weeks, because the provider will be grappling with the issue of whether 2 doses is better than 

no doses.
ACIP Meeting Summary January 12, 2022

24

Dr. Hills reiterated the concern about 2 doses in terms of variability by age. Some clinicians may 

not be comfortable telling an older person that they will have very good protection for 6 months 

after the second dose. A person who is traveling for 8 months as opposed to 1 month is going to 

have variable seropositivity over that period. This was one of the WG’s considerations for the 

importance of receiving the third dose if at all possible. The FDA-approved schedule is for 3 

doses. All of this information will be made very clear in the MMWR documents.

Dr. Daley emphasized that if possible, ACIP should strive for consistency in the way they 

approach vaccines recommended for international travelers. It seemed to him that clinical 

decision-making was not designed or intended for this purpose. It was striking that there were 

different interpretations of clinical decision-making among WG and ACIP members, implying 

that there also would be different interpretations by providers and patients. To him this boiled 

down to what he would say to the patient in front of him who self-identifies as going to a highrisk area, so he was leaning toward “recommended.”

Dr. Poehling noted that one of the conversations the WG had was that some people will present 

who will be able to get only 2 doses before departing the US. Those who are going to be in an 

endemic area for a long time can get their third and booster doses in that nation.

Dr. Hills presented some additional data that may help the ACIP members understand why the 

WG proposed “shared clinical decision-making.” Referring to Slides 103, 104, and 107, she 

pointed out that the problem with proposing a “recommendation” was that it would be difficult to 

define high-risk groups and then make a recommendation for those groups without the 

conversation happening between the traveler and the HCP. There are no apparent cutoffs in 

terms of age, duration of travel, undertaking high-risk activities, et cetera that would make sense 

to include in recommendations. For the 11 US travelers with TBE, the median duration of travel 

was 18 days or roughly 2.5 weeks. The range of travel duration was from 7 days up to 2 

months. What did appear to be more important than duration were the activities in which 

travelers were involved, but there was still variability within that whole group. Activities were 

unavailable to for 3 of the 11, but the remaining 8 travelers all reported activities that put them at 

higher risk for the tick bites (3 hiking, 2 substantial outdoor exposure in rural areas, 1 camping, 

1 fishing, 1 trail running). While activities were important, they did not define the whole group. 

Given the small number of cases, the WG was reluctant to recommend anyone going to go to 

Europe who thinks they might hike once to be vaccinated. This led to the WG’s consideration 

that it would be better to propose shared clinical decision-making, so that the provider can have 

a discussion with the traveler. The WG also considered whether the vaccine should be 

recommended to everyone moving to a TBE endemic country to take up residence since the 

increased duration of time in an endemic area might increase their risk. However, it is more 

related to their activities than their duration of travel. Unlike mosquitoes, one must go into a tick 

habitat to be exposed to ticks. The vast majority of people who are traveling to Europe are not 

going to be at risk. Again, even the European recommendations are not uniform—even for 

those living in areas with TBE virus transmission. There are some major limitations with trying to 

estimate the TBE risk for US travelers to Europe or China. Multiple assumptions had to be 

incorporated because some of the data needed for the calculation were lacking. Percentages 

were not available for all travelers to Europe who visit at least 1 TBE endemic country, visit an 

endemic area within a TBE endemic country, and/or undertake an activity that might put them at 

exposure to the risk of exposure to ticks. Acknowledging the major limitations up front and 

thinking about all travelers to Europe, including Russia and China, the risk is about 1 TBE case 

per 37 million US citizen trips to Europe and China overall. That is clearly a major underestimate 

because many countries in Europe have no transmission or only sporadic transmission. Though 
ACIP Meeting Summary January 12, 2022

25

many travelers would not be at risk, they have to be included in the denominator for that 

estimate. If the information is incorporated that 78% of trips are during the TBE virus 

transmission season, which is supported by some survey data from the National Travel and 

Tourism Office (NTTO), and an assumption that 50% of trips involve travel to at least 1 TBE 

endemic area within Europe or China, the risk is 1 case per 15 million trips for travelers to 

endemic areas during the transmission season. Picking up on an earlier comment that ACIP 

wants to make sure that the recommendations are targeting the appropriate travelers since the 

risk for US travelers is minimal, it is going to be impossible to define clearly which travelers 

might need to be vaccinated. Based on the NTTO survey data that say about 15% of travelers

to Europe will be exposed to ticks based on undertaking certain activities (e.g., camping, hiking, 

hunting, fishing, visiting a national park, visiting rural areas, et cetera), the risk comes down to 1 

case per 2 million trips for travelers who visit an endemic area within a TBE endemic country 

during the transmission season and undertake an at-risk activity. If the assumption is included 

that there might be 10 times as many TBE cases occurring than are diagnosed, which is 

unsupported by data, this may be an overestimate. CDC is the only place in the US where 

diagnostic testing for TBE is done and the agency receives only about 10 to 15 samples per 

year for testing. Incorporating that assumption, the risk is 1 per 219,000 trips for travelers

who visit an endemic area within a TBE endemic country during the TBE transmission season. 

The available data were highly influential in the WG’s desire to propose shared clinical decisionmaking rather than potentially misleading the traveling population by suggesting that everyone 

going to Southern Germany, for example, may want to be vaccinated. A lot of factors are likely 

to go into shared decision-making in addition to a traveler’s specific itinerary, such as their 

intended activities, individual personal perception, tolerance of risk, et cetera.

Dr. Loehr emphasized that they should make a distinction between risk and the 

recommendation for the vaccine. If someone has a high enough risk, they probably should get 

the vaccine and he was willing to recommend that. Talking about shared decision-making to 

decide whether someone has a certain amount of risk is not what he considers to be the 

concept of shared decision-making in the ACIP arena. His concept of shared decision-making

in the ACIP arena is situations in which the risk/benefit analysis of the benefit of the vaccine are 

so close that reasonable people would make different decisions. If they were arguing about 

shared decision-making being about risk, that was not what he thought they should be arguing 

about. They should be talking about recommending the vaccine for those who are at risk.

Dr. Bell agreed with the importance of ACIP being clear in their thinking about when to 

recommend shared clinical decision-making, and she agreed with the overall concept. In this 

situation, the more she listened to Dr. Hills and the point that Dr. Kotton made, it was not 

entirely clear to him that they actually could characterize the risk clearly. It sounded in some 

ways like this is a rare enough disease that there is not a good understanding of the variables 

about who should get this vaccine and who should not. Perhaps there may be an argument

for emphasizing other prevention strategies versus vaccination. She agreed with the points 

made about differentiating between making a recommendation in the context a travel vaccine 

when the risk is clear. Based on the information presented, a narrow population would be 

impacted.
ACIP Meeting Summary January 12, 2022

26

INFLUENZA VACCINE

Session Introduction

H. Keipp Talbot, MD, MPH (ACIP, WG Chair) introduced this session, the focus of which was 

on influenza vaccines for older adults. She reported that recent WG activities have included 

ongoing discussions of the systematic review of influenza vaccines for older adults referred to 

as “enhanced vaccines” and examination of the evidence for high-dose inactivated, adjuvanted, 

and recombinant vaccines. She reminded everyone that while influenza vaccine is often thought 

of as one vaccine, it is actually a different vaccine each year with 4 different strains. There also 

are different manufacturing methods, which makes influenza vaccines complex. 

Influenza Vaccines for Older Adults

Dr. Lisa Grohskopf (CDC/NCIRD) presented on influenza vaccines for older adults in terms of 

the burden of influenza among older adults aged 65 years and older (though some studies may 

have slightly different age ranges), influenza vaccine efficacy/effectiveness among older adults, 

challenges in comparing influenza vaccines, and an initial overview of the retrieved findings 

from the systematic review. She explained that the presentation of the systematic review would 

be split between 2 meetings due to the large amount of content. Adults ≥65 years of age have 

long been recognized as being at increased risk of severe illness, hospitalization, and death 

from influenza and were among the groups that have been included since one of the very first 

recommendations made by the federal government in the US for routine vaccination of the 

civilian population. While there had been periodic recommendations previously for pandemics, 

the Surgeon General’s Recommendation for Influenza Immunization—United States, 196010

was published as a follow-on to everything that occurred during the 1957 pandemic. Adults ≥65

years of age were among the 3 groups addressed in the report and have remained a focus 

since that time.

Based on surveillance data for the last 4 seasons (2016-2017 through 2019-2020) with 

substantial influenza activity from FluSurv-NET, a surveillance system for laboratory-confirmed 

influenza-associated hospitalizations that is updated weekly during influenza season, the 

highest burden of cumulative hospitalization is borne by persons ≥65 years of age compared to 

younger adults. Data from the 2013-2014 season through the 2019-2020 season illustrate that 

even though this age group does tend to have the highest burden, there is variability from 

season-to-season in terms of severity. To some degree, though not completely fool-proof, it can 

be assumed generally that H3N2 seasons are likely to be more severe and may be associated

with more hospitalizations. H1N1 seasons tend to be somewhat milder, though not always.

If you can hit the next slide. The 2018-2019 season was interesting in that it had an early H1N1 

prominence and then about midway changed to H3N2, with cumulative hospitalizations 

increasing around the February/March timeframe. Older adults were at highest risk for 

influenza-related deaths in the population during H3N2 predominant seasons.

10 Burney LE, Public Health Reports, October 1960, Vol. 75(10), page 944 
ACIP Meeting Summary January 12, 2022

27

Moving to influenza vaccine efficacy/effectiveness among older adults, this population also 

tends to be a group for which vaccines do not work as well as in younger age groups. Data from 

the CDC US Flu VE Network summarizing the overall VE for seasons 2011-2012 through 2019-

2020 reflect striking differences between those 65 years and older group and the general 

population.11 Fortunately, there are many doses of influenza vaccine among a variety of brands

and types. While there were 13 unique brands at one time, this season there are 9. This is due 

largely to phase-out of trivalent vaccines with one B strain over the last few years in favor of 

quadrivalent vaccines with 2 B strains. All 9 of the vaccines currently available are quadrivalent

for the first time. Persons ≥65 years of age are eligible to receive a vaccine from 8 of the 9 

available formulations based strictly on FDA-approved age indications. The only exception is the 

FluMist® Quadrivalent, which is licensed only for persons aged 2-49 years.

For purposes of the upcoming discussion, the focus was on 3 types of vaccines that are of 

particular interest for the systematic review. These include Fluad® Quadrivalent and its trivalent 

predecessor Fluad® licensed for persons 65 years of age and older, Fluzone® High-Dose 

Quadrivalent and its trivalent predecessor Fluzone® High-dose also licensed for persons 65

years of age and older, and Flublok® Quadrivalent and its trivalent predecessor Flublok®

licensed for persons 18 years of age and older. The high-dose inactivated influenza vaccine 

(HD-IIV3 or Fluzone® High-Dose) was approved in the US in 2009. It was replaced with HD-IIV4 

Fluzone® High-Dose Quadrivalent after that new vaccine was approved in 2020 and was first 

available for the 2020-2021 season. This vaccine contains 4 times the quantity of hemagglutinin 

per vaccine virus compared with standard-dose inactivated vaccines. That is 60μg per virus as 

opposed to 15μg, which is to address the issue that those 65 years of age and older tend not to 

respond as well to influenza vaccines. HD-IIV3 demonstrated superior efficacy to standard-dose

FluZone® (SD-IIV3) in a randomized clinical trial conducted among approximately 32,000

participants aged ≥65 years over the 2 influenza seasons of 2011-2012 and 2012-2013.

Subsequently, HD-IIV4 was approved after demonstrating non-inferior immunogenicity to HDIIV3 for the 3 viruses common to both vaccines, and superior immunogenicity to the additional B 

viruses not present in the trivalent comparators.

The MF59-adjuvanted inactivated influenza vaccine is the US’s only adjuvanted influenza 

vaccine. For this discussion, there are aIIV3 (Fluad®) and aIIV4 (Fluad® Quadrivalent). Though 

aIIV3 was approved in the US in 2016 and initially available in the 2016-2017 season, it was in 

use in Europe as early as 1997. aIIV4 was approved in 2020. While both vaccines were 

available in the 2020-2021 season, only aIIV4 is currently available. This vaccine contains the 

lipid-in water adjuvant MF59 as a means to help promote a stronger immune response in people 

65 years of age and older. The quadrivalent version was licensed on the basis of favorable 

safety compared with Tdap in a randomized trial of 6,740 persons ages ≥65 years over 2 

seasons (Northern Hemisphere 2016-2017 and Southern Hemisphere 2017). For this particular 

trial, the primary efficacy endpoints were not met as 88% of viruses from culture-confirmed

influenza cases in the aIIV4 arm were antigenically mismatched. Efficacy was higher against 

illness that was defined by a higher fever.

FluBlok® and Flublok® Quadrivalent are recombinant influenza vaccines (RIVs). The 

recombinant trivalent, RIV3, was first approved in 2013. It was not licensed for persons 65 years 

of age and older right away. Initially. It was approved for persons 18-49 years of age. Within

about a year, persons ≥50 years of age were added. RIV4 was approved in 2017 and was 

available alongside RIV3 for 1 season before a switch was made to RIV4, which has been the 

11 https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html 
ACIP Meeting Summary January 12, 2022

28

only RIV available since 2018-2019. RIV4 is a somewhat unique vaccine in that it does not use 

influenza viruses in its manufacture. It contains hemagglutinin, which is the primary antigen

that is responsible for promoting and neutralizing antibody response. Instead of getting that from 

actual influenza viruses, it is produced by recombinant technology without the use of influenza

viruses or eggs. The main efficacy study was conducted with RIV4, which demonstrated efficacy 

relative to SD-IIV4 in a randomized study conducted among approximately 8,600 persons aged 

≥50 years over the 2014-2015 season. 

HD-IIV4 (Fluzone® High-Dose Quadrivalent), aIIV4 (Fluad® Quadrivalent), and RIV4 (Flublok®

Quadrivalent) have been available in the US for a number of seasons. There are studies

supporting the relative benefits of each. The ACIP has not yet made a preferential 

recommendation for any of these vaccines over any other vaccines. The recommendation is 

that any IIV or RIV vaccine is appropriate as long as it is an age-appropriate vaccine, and that 

vaccination should not be delayed to find a specific vaccine when an appropriate vaccine is 

available. For the last several seasons, there has been discussion in the literature in terms of 

the studies supporting the relative benefits and the fact that the number, size, and designs of 

these studies vary. The guidance also has pointed out that comparisons among these 3 

vaccines against one another versus laboratory-confirmed influenza outcomes are limited. More 

recently with the advent of the quadrivalent formulations of these more enhanced vaccines, the 

guidance also points out that most of the accumulative evidence focuses on HD-IIV3 and aIIV, 

which are now exclusively available as quadrivalent formulations for which limited research and 

data have accumulated.

There are a number of challenges inherent in comparing different influenza vaccines with one 

another. Chief among these is that many elements of influenza vary and can cause VE to vary 

in any given study. These include varying circulating virus types and subtypes, constant virus 

mutations and varying degrees of match each season, and the fact that neither of these can be 

predicted ahead of the season. Influenza vaccine viruses are generally chosen by the World 

Health Organization (WHO) for the Northern Hemisphere in late February and the FDA meets 

about that in March. This allows sufficient lead time for vaccine to be produced when the season 

starts in the Fall. Since these viruses are constantly on the move, this is difficult sometimes to 

predict in some seasons. There also are host factors such as age/immunosenesence, chronic 

medical conditions that can interfere with VE, past influenza illnesses and exposures and their 

impact, and previous vaccination history. For this discussion, most important are viral factors 

and the simple fact that it is not possible to predict what the influenza is going to be like from 

season- to-season.

In addition to the fact that VE varies from season-to-season, VE is not static from one season to 

the next. In addition to variance in the general VE of an influenza vaccine, the relative VE (rVE) 

of influenza vaccines compared to one another also varies. Comparing the same 2 vaccines in 

one season and then the next might not have the same result as illustrated by this example of 

an analysis of CMS data by Izurieta et al:
ACIP Meeting Summary January 12, 2022

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Izurieta et al have performed 3 consecutive analyses of CMS data for 2017-2018, 2018-2019, 

and 2019-2020 seasons.12 These datasets included 12-13 million people aged 65 years and 

older each season. The analyses compared multiple vaccine types against one another.

Because this is a retrospective cohort study, it was not practical to have a laboratory-confirmed 

influenza outcome. Instead, the primary outcome was VE against influenza-associated hospital

encounters, including inpatient stays and emergency department (ED) visits. Other outcomes

also were analyzed for each of the 3 papers, which were defined by International Classification 

of Diseases, Ninth Revision (ICD-9) influenza codes. For 2017-2018 versus 2018-2019 versus 

2019-2020, there was some variability in the point estimate of the rVE from one season to the 

next. These were all rVE for each vaccine against an egg-based SD-IIV4 vaccine. Of note, there 

were insufficient uptake of RIV4 in the CMS system to be able to generate a reliable VE 

estimate for the first 2 seasons. Given the influenza activity in 2020-2021, there probably will not

be similar estimates from the CMS system or the Flu VE Network. But this is all to just illustrate 

that relative VE varies as well.

The challenges in comparing multiple vaccines with one another and the fact that VE varies

raises some considerations when reviewing the literature. Data from one or a few seasons

in any given study might not generalize to all or most seasons. Ideally, data from high-quality, 

randomized studies conducted over as many seasons as possible are preferred for making 

health policy decisions. Unfortunately, common study designs, including randomized studies, 

are associated with some tradeoffs. Randomized studies generally provide the highest quality 

data in terms of being able to control for potential biases and confounding. They are generally 

less feasible to conduct over successive seasons, and they are rather expensive due to large 

sample sizes. While there are examples of RCTs performed over 2 to 3 seasons, conducting 

them longer than that is typically not practical. Although these studies are less subject to bias

and create higher quality data, they are not as feasible to conduct over multiple seasons as 

observational studies. There are networks in the US like the Flu VE Network and the 

Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) that assess hospitalized 

influenza among adults, Influenza Monitoring Vaccine Effectiveness (I-MOVE) in Europe, and 

the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). These and other 

networks use observational methods to examine VE over sequential years. While observational 

studies are more feasible to conduct over successive seasons using similar methods, they also 

are more subject to bias, produce lesser-quality data, and can be constrained by uptake of the 

vaccine(s) of interest.

To this a little further to illustrate some of the issues that the WG has observed in the context of 

the literature they are reviewing, considering observational designs means dealing with more 

variability in study designs, differences in outcomes and analytic methods, and other tradeoffs. 

Most of what the WG is dealing with in their particular realm of retrieved papers are

retrospective cohort studies and a lower proportion of case-control studies. An advantage of the 

case-control studies is that generally, they have laboratory-confirmed outcomes. A drawback

with these studies is that they often have smaller sample sizes and event counts. For example, 

the sample sizes might be in the hundreds to thousands. Retrospective cohort studies make up 

the bulk of the observational studies the WG has been reviewing. An advantage with these is 

that they potentially can have very large sample sizes in the tens of thousands to millions. The 

Izurieta CMS analyses mentioned earlier included 12-13 million people per season, which is a 

sizable number of observations. A disadvantage of retrospective cohort studies is that they are 

probably not practical to carry out a study like this and expect to have laboratory-confirmed 

influenza outcomes. These generally include diagnostic code-defined outcomes that are less 

12 JID 2019;220:1955-1964; JID 2020;222:278-287; CID 2021;73(11):e4251-e4259 
ACIP Meeting Summary January 12, 2022

30

specific and have greater potential for misclassification and bias than there would be with a 

laboratory-confirmed influenza study.

Before summarizing the literature, Dr. Grohskopf elaborated on considerations regarding the 

meaning of rVE, given that it is another one of the challenges associated with comparing 

vaccines. Although the WG’s review includes studies of the vaccines of interest against no 

vaccine, placebo, and non-influenza control vaccines that would generate an absolute VE for 

those vaccines, those studies are somewhat in the minority. While the WG will be summarizing 

those with all of the EtR Framework tables and with the materials that will be presented during 

the next ACIP meeting, the WG is considering rVE estimates since they are assessing this from 

a policy standpoint. The formula for rVE is shown here, with VE is illustrated by a graphic 

courtesy of Dr. Jill Ferdinands:

 

 

One of the interesting qualities of this particular calculation is that for any given fixed difference 

between the new vaccine and the standard vaccine is represented by the mountaineer’s stride 

as he is climbing up the mountain. For any specific fixed difference in new versus standard VE, 

what the relative VE calculates out to be will depend on how high he already is up the mountain.

VE is relative, varies, and it will be associated with baseline VE. In each of 3 scenarios, the 

difference between the standard vaccine VE and the new vaccine VE is 20% or 0.2. Starting 

with a baseline VE of 20% calculates outs to a rVE of 25%. If you start out with that same

difference between the 2 vaccines with a baseline VE of 40%, rVE would be 33%. Beginning 

with a baseline of 75% with a difference of 20% would result in rVE of 80%. 

Some considerations for rVE specifically when dealing with a disease state for which baseline 

VE varies from season-to-season are: 1) the higher the effectiveness of the standard

(comparator) vaccine, the higher the rVE for the same increase in absolute VE (i.e., the size of 

the relative VE depends on the starting point); and 2) it is difficult to compare rVE from different 

seasons when the VE of the comparator vaccine varies by season. 
ACIP Meeting Summary January 12, 2022

31

Now turning to an overview of the first part of the retrieved literature for the systematic review of 

influenza vaccines for older adults. The review question regards whether the relative benefits

and harms HD-IIV, aIIV, and RIV as compared with one another and with other influenza 

vaccines favor the use of any one or more of these vaccines over other age-appropriate 

influenza vaccines for persons ≥65 years of age. In terms of the PICO elements, the population 

is adults ≥65 years of age. The interventions of interest include HD-IIV, aIIV, and RIV either USlicensed or similar in formulation or manufacturer to US-licensed formulations. Comparators

include other trivalent or quadrivalent vaccines (US-licensed or similar in formulation and 

manufacture to US-licensed vaccines), non-influenza control vaccine, placebo, and no vaccine. 

After a great deal of discussion in 2019 and leading into 2020, the WG selected a total of 8 

outcomes, 4 efficacy/effectiveness and 4 safety outcomes. The efficacy/effectiveness outcomes

include outcomes that apply to all viral types and subtypes and are influenza illness, influenzaassociated outpatient or ED visits, influenza-associated hospitalizations, and influenzaassociated deaths. Safety outcomes include any solicited systemic AEs of Grade 3 or higher, 

any solicited injection site AEs of Grade 3 or higher, any SAEs, and Guillain–Barré syndrome 

(GBS). 

A total of 6 bibliographic databases were searched as far back as 1990, given that the WG felt

that to encompass the pre-licensure period for the 3 vaccines of interest, the beginning of the 

range should be set at the time of Fluad® licensure in Europe in 1997. The earliest references

they could find scoping PubMed for MF59 were around 1995. They buffered that with an

additional 5 years to 1990. There were 2 search strategies used, the first that searched articles 

in general and the second for review articles alone in order to be able to look for potentially 

missed articles in the bibliographic references of those reviews. A total of 3 searches were 

conducted in February 2020, February 2021, and most recently in the beginning of September 

2021 to update the literature as it was published. A total of 10,808 references initially were

found. An additional 160 were identified through a search of bibliographies of review articles

or through reports that were forwarded on after screening to full-text review. After removing 

duplicate reports, that number is 799. The WG has 10,169 subjected title abstract screens, of 

which 6,624 were deemed not relevant. A fairly large number of 3,545 went to full-text review, 

given that previous reviews revealed that it can be very difficult sometimes to make a judgement 

based on a title and an abstract. Thus, the WG erred on the side of reviewing full-text when in 

doubt. Of the 3,545 reports that went to full-text, 3,468 were excluded. Amazingly among all of 

the articles the WG requested, the library was unable to locate only about 15. They ended up 

with 77 included reports, which comprised 34 individually randomized studies, 2 cluster 

randomized studies, and 41 observational studies.

None of the randomized studies address outpatient medical visits or deaths, which fits with the 

design of these studies. This is not a real-life activity as part of a clinical trial. Most of these

studies were designed such that people signed up for the trial, received their vaccine, and were 

asked to report on such things as instances of respiratory illness—using some criteria so that 

they could be swabbed. The primary outcome for most of these studies is influenza illnesses. A 

relatively small number have an outcome of hospitalizations. There are just 4 studies for 

hospitalizations, which include 2 high-dose versus standard-dose comparisons, 1 clusterrandomized study, and 1 high-dose versus quadrivalent comparison. There is 1 clusterrandomized trial looking at adjuvanted versus standard-dose vaccine. 
ACIP Meeting Summary January 12, 2022

32

This set of charts attempts to illustrate VE data dispersed over multiple seasons in individuallyrandomized studies. For each of the 6 vaccine comparisons here, without regard to whether 

they are trivalent or quadrivalent, there is a histogram that shows the number of studies on the 

x-axis and the seasons on the y-axis. The small blue box in the upper right-hand corner 

provides an idea of the number of participants in those studies: 

Notably, none of the columns in the bar charts go above 1 and there is not broad representation 

of seasons for the most part in these individually-randomized studies. The 2 outcomes are 

influenza illnesses and influenza-associated hospitalizations. To summarize the HD-IIV versus 

SD-IIV comparisons, there were 2 studies from Diaz/Granados (2013) and Diaz/Granados 

(2014). There are a lot of similarities in the designs of these 2 studies. They both compare HDIIV3 with SD-IIV3. The Diaz/Granados 2013 study was initiated during the 2009-2010 pandemic, 

which led to the consequence that there was circulating virus which was much different from 

what was anticipated to circulate, and there were no matched positive viruses isolated from 

cases. Therefore, it is not possible to draw inferences from that study. There also is a fairly wide 

confidence interval for the VE estimate.

The similarly designed Diaz/Granados 2014 study began in the 2011-2012 season and also 

includes the 2012-2013 season, so it is a 2-season study. It also compares HD-IIV3 to SD-IIV3. 

This study had nearly 32,000 people enrolled, with approximately 15,900 in each group. The 

primary outcome for this study was PCR or culture-confirmed influenza-like illness (ILI) due to 

any viral type or subtype. There are separate estimates for each of the 2 seasons and a 

combined estimate for both seasons combined, which was the main finding reported in their 

abstract. A relative VE of 24.2% for the combined seasons, which was statistically significant

based on the confidence interval. There were two other ILI definitions used in the analyses

for this paper that were somewhat more general than the previous one. One was a modified 

CDC ILI definition in that the temperature criterion was lowered somewhat because older adults 

tend not to be as likely to have a fever response with infectious diseases, including influenza.

There also was an estimate for that definition for both seasons, as well as for a third definition of 

respiratory illness, which is the most general definition. That definition was used to trigger 

people getting swabbed and investigated to determine whether they had influenza. Comparing 

just the point estimates for those 3 definitions going from more specific to less specific, the point 

estimate of the VE decreases.
ACIP Meeting Summary January 12, 2022

33

For the influenza illness outcome for aIIV compared to SD-IIV, there were 2 studies. Both were 

individually-randomized trials. Song 2013 was conducted during the 2009-2010 season. It is a 

relatively small study of only 76 subjects. The paper indicates that they asked people with 

symptoms of ILI to return to be swabbed, with ILI confirmed by a virologic testing. The specific 

nature of that virologic testing was not specified. Unfortunately, this study is not informative in 

that no laboratory-confirmed influenza was observed during follow-up. The second study by 

Frey et al., 2014 was conducted during the 2010-2011 season. This was the major safety study 

for this vaccine versus SD-IIV inactivated unadjuvanted vaccine. Roughly 7,000 people were 

enrolled in this study. While this study assessed ILI, it used a symptom-defined definition and no 

laboratory confirmation was performed. The relative VE was 9 and it was not statistically

significant.

There is 1 other aIIV RCT by Beran et al., which is not a rVE study. It was a study of aIIV 

compared to Tdap as a non-influenza control vaccine. This included roughly 6,700 people.

The primary outcome was PCR-confirmed ILI due to any viral type or subtype associated

with protocol-defined ILI. For that primary outcome, the efficacy endpoint was not reached. VE 

was 19.8 with a confidence interval that spans the null. Again, this illustrates that when

definitions are changed, VE looks different. There is also a modified CDC-defined ILI, similar to 

what was in the Diaz/Granados paper, and a WHO-defined ILI, which is probably the most 

specific definition of the 3. This study did have higher point estimates, with statistically 

significant results for those outcomes.

There are 2 papers for RIV versus SD-IIV, Keitel (2009) and Dunkle (2017). Keitel et al. (2009) 

was a pre-licensure study examining RIV3 versus SD-IIV3. This study had an ILI outcome 

similar to other designs that asked people to present for testing, in this case with culture rather 

PCR. This study had a relatively small number of culture-confirmed ILI cases, so rVE was not 

calculated. There was 1 instance out of 436 in the RIV3 group for 0.2% and 2 in the SD-IIV3 

group for 0.55%. The larger study, Dunkle et al. (2017), was one of the major studies for

licensure of RIV4. This study was conducted over the 2014-2015 season and compared RIV4 to 

SD-IIV4 among 8,600 people. The primary outcome was ILI associated with PCR-confirmed 

influenza. This study enrolled people 50 years of age and older, so it has a slightly different age 

range than most of the other studies the WG is reviewing. This study had a statistically 

significant rVE of 30%. The rVE for those ≥65 years was 17% and was not statistically 

significant. Overall, for the broader population, there is some evidence of improved efficacy 

among older adults.

For comparisons of the vaccines of interest (HD-IIV, aIIV, and RIV) against each other, there 

was 1 individually-randomized study by Belongia et al (2020) that was conducted over the 2017-

2018 season. This was primarily an immunogenicity study, the efficacy outcome was

exploratory, and the sample size is small. There were 99 subjects, with 29 each in the HD-IIV

and aIIV groups and 30 in the RIV. The study does provide some data on laboratory-confirmed 

influenza. This study will be pooled with other results that are compatible for pooling. In this 

study, there were 8 instances of PCR-confirmed ILI, 1 in the HD-IIV, 3 in the aIIV group, and 4 

in the RIV group. 

Looking now at influenza-associated hospitalizations, a topic of discussion in the WG for many 

years, it is obviously very important to prevent all influenza. This is particularly important in older 

populations because older adults can become quite ill. Hospitalization is an important milestone 

and marker for severe illness. There have been a lot of questions about how well influenza 

vaccines prevent severe illness. For this particular outcome, the WG identified studies that differ

from the studies just shown. There are 2 individually-randomized trials and 2 cluster-randomized 
ACIP Meeting Summary January 12, 2022

34

trials. The individually-randomized trials are both comparisons of HD-IIV compared to SD-IIV. 

There is 1 cluster-randomized trial of HD-IIV compared to SD-IIV and 1 of aIIV versus SD-IIV. 

No more than one season is represented at a time. 

Beginning with the individually-randomized study by Diaz/Granados 2015, this is a

supplementary analysis of the Diaz/Granados 2014 data—the large 32,000-person RCT 

conducted over the 2011-2012 and 2012-2013 seasons. That study and its original outcomes 

did not include influenza-associated hospitalizations. However, it did include all-caused 

hospitalizations. This analysis used a method to try to get an idea of hospitalizations that 

possibly were related to influenza. It involved examination of SAEs from Diaz/Granados 2014

for which primary terms were adjudicated as possibly being related to influenza and divided up 

into 4 categories: Influenza Events, Pneumonia Events, Asthma/Bronchial Events, and Other 

Respiratory Events. These seem to be the most likely to be potentially be applied to an 

influenza illness event. Three were not statistically significant results for any of these, though 

the point estimates indicate that point estimates below 1 are good in terms of some diminished 

likelihood of influenza-associated hospitalization with a high-dose vaccine. The category of 

Pneumonia Events was statistically significant, but was not a primary study outcome. These 

events were adjudicated before study unblinding.

Vardeny et al (2021) is 3-season study (2016-2017, 2017-2018, and 2018-2019) that examined 

HD-IIV3 compared to SD-IIV4. This is an interesting study in that the criteria for admission are 

less based on age than they are on previous history of cardiac or congestive heart failure (CHF) 

hospitalizations. Therefore, this study has a somewhat broader age range. The interquartile age 

range is 58-74 years for both groups. The primary outcome were not influenza-related

hospitalizations. It was more cardiovascular-related hospitalizations. As described in the

supplementary methods for the protocol, a group of clinicians examined hospitalizations and 

determined whether they were primarily due to influenza or primarily due to pneumonia. There is

not a rate ratio or risk ratio calculated for these comparisons, just p-values. Comparing the

proportion or percent of events in each group for pneumonia or influenza, neither is statistically 

significant.

The last 2 studies for this proportion of the WG’s initial findings were cluster-randomized studies

by Gravenstein et al (2017) of HD-IIV3 versus SD-IIV3 and McConeghy et al (2020) of aIIV3 

versus SD-IIV3. These studies were conducted in a network of approximately 823 nursing

homes in the US. Randomization was is based on the level of the facility, so some facilities

received HD-IIV, some received SD-IIV, some received adjuvanted, and some received 

unadjuvanted. The outcomes were pneumonia and influenza-coded hospitalizations, both of 

which showed a statistically significant decreased risk of that particular outcome. It is not a labconfirmed outcome, but it is some evidence toward hospitalization.

In summary of the randomized studies, the WG has data available comparing HD-IIV and RIV

versus SD-IIVs against laboratory-confirmed outcomes. They also have relatively more limited

comparisons of aIIV versus SD-IIV against laboratory-confirmed influenza outcomes.

Comparisons of HD-IIV, aIIV, and RIV with one another are limited to 1 small study as an 

exploratory endpoint. Within each vaccine comparison, a limited number of seasons are 

represented. This is a potential limitation considering that influenza vaccine VE varies so much. 

The WG has no data on laboratory-confirmed influenza hospitalizations. The estimates on

hospitalizations from individually randomized studies do not come from primary analyses. 
ACIP Meeting Summary January 12, 2022

35

Discussion Summary

Dr. Poehling asked whether she was correct in understanding that the subcutaneous influenza

vaccine was not recommended for persons aged ≥65 years and if so, why it was not included.

Dr. Grohskopf indicated that the intradermal vaccine has not been marketed in the US for 

several seasons. It was in around 2011 in the US. FluZone intradermal and FluZone intradermal 

quadrivalent were only approved for persons aged 18-49 years, which had to do with the

populations in which it was studied. One issue with the intradermal vaccine is that the immune 

cells that are the targets are in a pretty specific layer and there is potentially some thinning of 

skin with age. There is a version of that vaccine with a higher antigen dose that is licensed in 

other countries for person 65 years of age and older. That was a higher antigen dose. Here, 

there was FluZone® intradermal with 9μg of antigen per virus, which is lower because not as

much is needed for intradermal as is needed with an intramuscular, which had 15μg. There was 

a version licensed for older adults in other countries that had 15μg. 

Dr. Long noted that it was somewhat difficult to keep a running tally about what the

preponderance of evidence shows. She asked whether Dr. Grohskopf could say, 

understandably with lots of exceptions, that there was suggestion across the studies that the

vaccines particularly formulated for older adults showed increased efficacy. 

Dr. Grohskopf said the best way to answer that was that there is variability. This was intended to 

be a brief overview. During the February meeting, the intent would be to discuss the metaanalysis. 

Dr. Caine asked whether any demographic and socioeconomic data would be provided since it 

is known that Black persons had the highest influenza-associated hospitalization rates across all 

of the last 10 influenza seasons. There also is a higher level of chronic medical illness among 

Black persons compared to their White counterparts.

Dr. Grohskopf indicated that the studies identified by the WG do not evaluate race as a primary 

variable, but most of them do examine race, particularly the CMS studies and the larger 

observational studies. All of the clinical trials will provide some discussion of the demographic 

data. All of the studies have various sub-analyses. For example, they may break the ages down 

into different groups. She did not immediately recall whether any of them performed specific 

analyses by race or ethnicity, but the WG can definitely start by looking at the make-up of these 

studies to try to delve into that further. 

Dr. Talbot added that there is not a lot of diversity in these studies. The COVID-19 vaccine

studies in adults over 65 years of age were some of the first to be better diversified. There is a 

lot more work to be done in that area in the influenza studies, and there is unlikely to be

significant data to pull out of the studies identified. 

Dr. Bell made a general overall comment about this whole enterprise that had been begun

looking at rVE, presumably with the idea of considering a preferential recommendation. She 

personally would appreciate a very robust discussion and examination of what the threshold for 

a preferential recommendation would be. While she recognized that it is all speculation, she 

anticipated that it would be easier for her to think about her vote on a topic like this if she has a 

clear understanding of at least what the experts and the WG think the implications of such a 

recommendation might be.
ACIP Meeting Summary January 12, 2022

36

HEPATITIS VACCINE

Session Introduction

Kevin Ault, MD (ACIP WG Chair) introduced this session, which focused on evaluation of the 

use of a 3-antigen HepB vaccine candidate (PreHevbrioTM) for adult vaccination. The FDA 

approved PreHevbrioTM on November 30, 2021.13 In terms of background, 2022 is the 40th

anniversary of the original Hepatitis B (HepB) vaccine. The rate of new infections in the US in 

the past 40 years has decreased by 90% because of these vaccines. The ACIP voted on 

November 3, 2021 to expand HepB coverage through a universal adult vaccination 

recommendation. Manufactured by Variation BioTechnologies Inc. (VBI Vaccines, Inc.), the 

indication for PreHevbrioTM is for prevention of infection caused by all known subtypes of the 

HepB virus in adults 18 years and older.

Safety & Immunogenicity of a 3-Antigen Hepatitis B Vaccine, PreHevbrioTM 

Dr. Francisco Diaz-Mitoma, MD, PhD (VBI Vaccines Inc.) present on the safety and 

immunogenicity of PreHevbrioTM. As a new entrant to the US, he took a moment to introduce 

the company. VBI Vaccines, Inc. is a biotechnology company. Their first product is 

PreHevbrioTM, a recommended HepB vaccine approved by FDA. VBI Vaccines, Inc. has a 

pipeline composed of several prophylactic and therapeutic vaccine candidates targeting

different infectious diseases and cancers. This is a global company with its corporate

headquarters in Cambridge, Massachusetts; research and development headquarters in 

Ottawa, Canada; and fully owned manufacturing and research facility in Rehovot, Israel where 

the HepB vaccine candidate is produced.

HepB remains a persistent US health problem that will require a new solution. There are

numerous challenges with HepB, including suboptimal surveillance, low awareness of infection, 

and vaccine uptake rates that have been persistently low at around 25%. Additionally, there has 

been an increase in acute cases of 11% in recent years with changes in the incidence and 

epidemiology, with half of cases occurring in adults 30-49 years of age. Despite these

challenges, there is renewed focus on HepB with ACIP’s vote for the universal vaccine 

recommendation and further surveillance guidelines. Additionally, the HHS has called

for a 90% reduction in cases by 2030. To achieve these goals, new public health tools are

needed.

To highlight the general features of the HepB virus that are relevant to the PreHevbrioTM, as

with other envelope viruses, the HepB virus has 3 main components: its genetic material, a 

capsid or core, and the envelope. The envelope has 3 distinct surface proteins: Small HBsAg 

envelope protein (S), Medium HBsAg envelope protein (Pre-S2), and Large HBsAg envelope 

protein (Pre-S1). The Pre-S proteins have a critical functional role in the recognition of the virus 

cell receptor. B cell epitopes present in the Pre-S domain elicit potent antibodies against the 

small S antigen, resulting in seroprotection against infection in HepB susceptible populations. In 

terms of features that differentiate PreHevbrioTMvaccine from others on the market, all available 

vaccines express the small S antigen. PreHevbrioTM is the only vaccine with a full set of 

envelope antigens, which is believed to lead to the potent immune response resulting in 

increased seroprotection. The Pre-S proteins have a critical functional role in the recognition of 

13 https://www.fda.gov/vaccines-blood-biologics/prehevbrio 
ACIP Meeting Summary January 12, 2022

37

HepB virus cell receptors. VBI Vaccines, Inc. believes that the immune epitopes present in the 

Pre-S domain elicit that potent immune response that results in protection against infection.

PreHevbrioTM is the only vaccine expressed in mammalian cells. The other vaccines are

expressed in yeast. PreHevbrioTM contains a common adjuvant, aluminum hydroxide, which has 

a good safety record and is also used in the standard-of-care vaccines. The adult dose contains 

10μg of antigen. In terms of the significance of these differentiating features and why it matters, 

the benefits are 3-fold. First, unlike currently available HepB vaccines containing the small S, 

the antigens in PreHevbrioTM vaccine resemble the naturally occurring mammalian glycosylation

with a similar glycosylation pattern and properly folded proteins representing linear and 

confirmational B cell epitopes able to elicit efficient immunogenicity. Second, Pre-S1 and Pre-S2 

regions are significantly more immunogenic at T and B cell levels than S. Pre-S1 and Pre-S2 

antigens can overcome non-responsiveness to S through expanded T cell epitopes and distinct 

regulation pathways. The efficiency of the Pre-S1 to elicit that immune response in nonresponders highlights the additional benefit of a vaccine with these components. Several animal 

model studies support these findings in terms of the pre-antigen confirmation, the mammalian 

cell derivation, and confirmed benefits that result in an increased protection. The Pre-S1 and 

Pre-S2 T helper and B cell epitopes result in antibodies that are required to prevent infection by 

all HepB virus genotypes. While the overall effect of vaccine escape mutants is likely low,

emergence of drug resistant mutants with alterations in “a” determinant of S protein is of some 

concern, Pre-S1 and pre-S2 epitopes may help reduce emergence of vaccine escape mutants

and may reduce risk of HBV infection caused by escape mutants. 

The 3-antigen HepB virus (HBV) vaccine has an extensive history. The US Phase 3 program 

delivered 2 pivotal studies, PROTECT and CONSTANT, that were designed to achieve 

licensure in adults in the US, Europe, and Canada. These were initiated at the end of 2017 and 

were completed in 2020. The US FDA approved PreHevbrio TM on November 30, 2021 for the 

prevention of infection caused by all known subtypes of HBV in adults aged 18 and older. The 

American Medical Association (AMA) Current Procedural Terminology (CPT®) Panel established 

unique CPT code for the 3-antigen HepB vaccinee (90759). The vaccine was designed and 

initially produced at the Weizmann Institute in Israel. Since 1989, 23 clinical studies have been 

performed in children and adults, resulting in initial market authorization in 2000 in Israel, where 

it currently has preferential adult recommendations for certain patients or groups. Approximately 

750,000 individuals have received a vaccine in Israel where the vaccine is licensed in 3 dose 

formulations: 

 2.5 μg & 5 μg HBsAg/0.5 mL (neonates, infants, and children)

 10 μg HBsAg/1 mL (adolescents and adults)

 High-dose 20 μg HBsAg/1 mL formulation, which also has been evaluated in several clinical 

studies 

The Phase 3 clinical program was comprised of the 2 pivotal studies, PROTECT and 

CONSTANT, which assessed immunogenicity and safety in comparison to the most frequently 

used standard-of-care vaccine. The PROTECT study was published in Lancet Infectious 

Diseases in May 2021 and the CONSTANT study was published by the JAMA Network on 

October 11, 2021. The PROTECT study is a multi-center double-blind randomized control study

conducted in 28 community clinics and academic hospitals in the US, Greenland, Canada, and 

Belgium. The study enrolled 1607 participants with an age range of 18-90 years. The co-primary 

endpoints are non-inferiority in adults aged 18 and older and superiority in adults 45 years of 

age and older. Secondary endpoints included safety, tolerability, and antibody concentration, 

kinetics of the seroprotection rate, and immunogenicity in subgroups. The CONSTANT study is 

a double-blind 4-arm lot-to-lot consistency study with a control. The study and size were
ACIP Meeting Summary January 12, 2022

38

expanded to complete the safety database requirements. Randomization was to 4 arms, with 1 

arm receiving the control vaccine and 3 arms receiving the candidate vaccine, with a total of 

2800 participants. The age range was 18-45 years. The primary endpoint was the geometric 

mean concentration (GMC) of antibodies across the 3 vaccine lots. Secondary endpoints were 

safety, tolerability, reactogencity, and seroprotection rate.

In terms of breakdown and subgroup distribution for the PROTECT study, 82% of the age 

cohort was older than 45 years. In PROTECT, 43% of participants were enrolled in the US. The 

US-based is racially and ethnically diversity. There is good representation of African American

and LatinX populations. In addition, 40% of the patients were enrolled in Europe and 16% in 

Canada. Of the participants, 95% completed the study. The CONSTANT enrolled 2838 

participants from 35 study sites, with 27% in the US and 70% in Europe. There were more 

participants from Europe, especially Finland. In Finland, HepB universal pediatric vaccination 

was only recommended in 2016, allowing the investigators to enroll a younger cohort aged 18-

45 years. All volunteers in this study were healthy and all potential participants with chronic 

health conditions were excluded, including people with a body mass index (BMI) higher than 30.

A critical endpoint of the pivotal program was to confirm the safety of the 3-antigen vaccine 

observed in previous clinical studies. The integrated safety analysis identified no unexpected 

reactogenicity. The vaccine was associated with increased rates of mild to moderate injection 

site pain, tenderness, and myalgia. This reactogenicity generally resolved without intervention in 

1 to 2 days. There was no increase in reactogenicity over the 3-dose vaccine schedule and 

there were lower rates of vaccine discontinuation. The rate of unsolicited AEs was similar

in both vaccine arms. There were no unexpected safety signals and there were no unusual 

patterns or concerning clusters of SAEs. There was no increased rate of medically attended 

adverse events (MAAEs) or new onset of chronic illness (NOCI) in comparison to the controlled 

vaccine arm.

Summarizing the safety data across both Phase 3 studies, there was a high completion rate in 

both studies and the most common finding was local reactogenicity that resolve with no

intervention. There was no difference in MAAEs between vaccine groups. SAEs were

uncommon with both vaccines and there was no clustering of AEs. There were 2 SAEs reported 

as possibly related, a severe gastroenteritis in PROTECT and an ankyloglossia (tongue-tie) in 

CONSTANT that upon independent review it was determined not to be vaccine-associated. 

There was 1 death in the CONSTANT study to a participant randomized to the PreHevbrioTM 

arm. The autopsy ruled that the death was due to pre-existing hypertrophic heart disease.

The PROTECT and CONSTANT studies analyzed the immunogenicity of PreHevbrioTM vaccine 

and the standard-of-care control. The co-primary endpoints were met 4 weeks after the third 

vaccination. These co-primary endpoints were based on the comparison between arms of the 

seroprotection rate represented by 10 milli-international units per milliliter (mUI/mL) units per 

milliliter of antibodies against the surface antigen, which represents protection against infection.

The first endpoint, non-inferiority in adults of all ages, was demonstrated with a between group 

difference of 14.9% in all adults in the per protocol set. This difference was sustained and 

slightly increased in the second endpoint and statistical and clinical superiority of PreHevbrioTM 

was demonstrated in older adults with a between group difference of 16% in the full analysis

set. 
ACIP Meeting Summary January 12, 2022

39

There was a difference in seroprotection rates between subgroups of interest. This improvement 

was sustained regardless of age, diabetes, or BMI. There are additional analysis showing that 

the improvement in seroprotection and antibody concentration were sustained regardless of 

alcohol consumption, smoking, gender, race, ethnicity, and/or geographic jurisdiction. Higher 

seroprotection rates were achieved with PreHevbrioTM after 2 and 3 doses in comparison to the 

control. In the PROTECT study, the difference after 2 doses was pronounced, with 87% versus 

39% seroprotection rates. In the CONSTANT study, PreHevbrioTM also achieved higher levels 

of seroprotection after 2 doses than the control at 90% versus 51%. Moreover, the

seroprotection rate was higher for PreHevbrioTM than the control at both time points and in all 

age cohorts. The seroprotection rate was higher after 1 dose and more than double after 2 

doses with PreHevbrioTM than with the control vaccine. In addition, the durability of

seroprotection was higher with PreHevbrioTM than with the control in all adults. The 

immunogenicity results of the CONSTANT study demonstrated a rapid and consistently high 

rate of seroprotection and higher concentration of antibodies than were achieved with 

PreHevbrioTM in young adults who were compared to the control vaccine. The primary endpoint 

of consistency was met.

PreHevbrioTM has expansive real-world experience, highlighted by 3 investigator-initiated 

studies in populations where there is particular concern from low or non-response to HepB 

vaccines in which PreHevbrioTM was able to circumvent non-response in the majority of 

patients. These 3 published studies demonstrate the benefits of a more potent HepB vaccine. 

Patients with end stage renal disease (ESRD) or human immunodeficiency virus (HIV) are 

particularly at risk of HepB virus exposure and the standard-of-care requires frequent serology 

testing. Often there is no seroprotection after a standard-of-care vaccination. In the renal failure 

study, these patients did not respond to a double dose of Engerix-B®. After 3 doses of 

PreHevbrioTM vaccine, a seroprotection rate of 86% was achieved versus the control of 56%.

Similarly, in the HIV positive patients, a high seroprotection rate was observed after 3 dose of 

the 3-antigen vaccine of 84% versus historical controls of 17% to 53%. In the third study, adults 

who did not respond to more than 3 doses of conventional yeast-derived HBV vaccines, 

achieved a seroprotection rate was 87% after 1 dose of PreHevbrioTM. 

To summarize, the safety profile of PreHevbrioTM is comparable to Engerix-B® and consistent 

with a 20-year known history and usage of the 3-antigen PreHevbrioTM HepB vaccine. There are 

higher rates of protection in all adults and robust immunogenicity across age cohorts. In 

particular, for older adults in whom immunosenescent is a concern, am improved response was 

observed in the studies of people 45 years of age and older and people 55 years of age and 

older. There was a rapid onset of protection for all ages and all time points. In particular, 90% of 

participants in the study aged 18-45 years reached seroprotection after 2 doses. Nearly half of 

all cases of HepB are occurring in this population of increased concern. There is improved 

immunogenicity in key high-risk population. Those with chronic conditions often have a

suboptimal response to vaccine, but there was improved seroprotection for people with both 

diabetes and obesity following receipt of PreHevbrioTM. There is a renewed focus on HepB with

new immunization and screening guidelines. These efforts will require new approaches and 

PreHevbrioTM is a public health tool to help achieve these goals. 
ACIP Meeting Summary January 12, 2022

40

Discussion Summary

Dr. Ault asked whether VBI Vaccines, Inc. has any data on PreHevbrioTM that are specific to 

pregnancy.

Dr. Diaz-Mitoma indicated that there were a handful of pregnancies in the study for whom no 

AEs were observed during the study. As part of their full licensure commitment, they are 

developing a protocol now that will be presented and submitted to the FDA as a pregnancy 

registry. Otherwise, there is limited experience thus far with pregnancy.

Dr. Sanchez noted that it seemed like PreHevbrioTM also has been used in neonates and is 

currently being used in Israel in neonates and infants. In addition, it seemed to him that S, PreS1, and Pre-S2 are distinctly different proteins. 

Dr. Diaz-Mitoma explained that this is one of the main differentiating features of PreHevbrioTM

vaccine. PreS1 is the largest protein that is approximately 226 amino acids in length. There is a 

unique overlapping region that is about 100 amino acids and there is a common region

for the small S. Similarly with Pre-S2, there is a very specific domain that is around 50 amino 

acids that is very specific for the Pre-S2 domain. A characteristic of these Pre-S domains is

that they contain very potent T cell helper and B cell epitopes. In terms of the experience with 

the neonate in Israel, the vaccine has been used as a birth vaccine for the last 20 years and it 

continues to be used in neonates and in children. It has been used extensively in pediatrics. In 

terms of the legacy studies, there are 23 clinical studies in addition to the 3 pivotal Phase 3 

studies. Of the 23 studies, 12 are in neonates or children. There is extensive literature about the 

use of this vaccine in Israel. In terms of FDA approval for newborn vaccination, VBI Vaccines, 

Inc. currently has a waiver from FDA for the pediatric indication and they remain open to further 

development, especially if there is interest from investigators who use them in populations 

where there is a need for an enhanced HepB vaccine.

Dr. Cineas requested a list of the groups for whom the PreHevbrioTM vaccine is recommended 

in Israel.

Dr. Diaz-Mitoma indicated that the vaccine has preferential use for healthcare workers, frontline 

responders, persons with ESRD, persons who are HIV-positive, and/or patients who have 

immunosuppression.

Dr. Kotton observed that the data looked good for ESRD and HIV, but wondered whether there 

are subgroups with organ transplants, more severely immunocompromised patients, patients 

receiving rituximab, and/or other highly challenging patients.

Dr. Diaz-Mitoma indicated that there have been very small investigator-initiated studies in 

transplant recipients, especially those with very profound immunosuppression like liver 

transplants in whom the results also have been positive. The higher dose formulation has been 

used in these studies. There is very limited information on the subgroups Dr. Kotton mentioned.

Dr. Lee asked whether there are post-market safety surveillance data available from other 

countries and whether the FDA approval includes a statement about pregnant women.
ACIP Meeting Summary January 12, 2022

41

Dr. Diaz-Mitoma explained that the main observations they have are from the periodic safety 

reports that have been submitted every 2 or 3 years to the Minister of Health in Israel over the 

last 15-20 years. Clustering of SAEs has not been observed in any of those reports. The FDA 

approval excludes pregnancy.

MATERNAL/PEDIATRIC RESPIRATORY SYNCYTIAL VIRUS (RSV) WG

Sarah S. Long, MD (ACIP WG Chair) introduced the newly formed Maternal/Pediatric RSV

WG. In term of the purposes of this WG, RSV is a major cause of lower respiratory illness, 

particularly among infants and children and among older adults and adults with chronic medical 

conditions. RSV vaccine and monoclonal antibody development has progressed in the past 

decade with over 40 candidate vaccines and monoclonal antibodies currently in development.

The target populations for whom these products are intended include infants and young

children, pregnant women, and older adults. It was the CDC’s decision to create 2 WGs. A 

different WG will consider older adults and immunocompromised persons. The new 

Maternal/Pediatric RSV WG will consider recommendations for use of RSV vaccines and 

monoclonal antibodies targeting protection of children aged <18 years. The goals of the 

Maternal/Pediatric RSV WG will be to: 1) review the epidemiology and burden of RSV disease 

in children and pregnant women; 2) review the efficacy immunogenicity, safety, and costeffectiveness of RSV vaccines and newly developed monoclonal antibody products in pregnant 

women and children; 3) provide evidence-based recommendations regarding use of RSV 

vaccines and newly developed monoclonal antibody products in pregnant women and children; 

and 4) identify areas in need of further research for informing potential future vaccine and

monoclonal antibody recommendations. Here is a snapshot of the products that are FDAapproved or in development: 
ACIP Meeting Summary January 12, 2022

42

The only approved product is the monoclonal antibody palivizumab, which is costly, is given in 5 

doses, and has only modest benefit in even preventing hospitalizations. It has been available

since 1998. The kinds of vaccines that are under study include live-attenuated/chimeric, proteinbased, nucleic acid, and recombinant vector vaccines. The WG will focus on those that are in 

Phase 3 or later trials. Note that the products are marked with either E, M, or P. These 

represent the target populations. E is for elderly populations, M signifies maternal immunization, 

and P is for pediatric preparations. The WG anticipates that a Biologics License Application 

(BLA) will be submitted for a monoclonal antibody and 2 vaccines within the next 12 to 16 

months.

The WG includes 2 other members of ACIP, 8 ex officio members, and 5 liaison members along 

with an elite group of expert consultant and CDC staff. The WG has convened calls from 

October 2021-January 2022 during which the members have reviewed the burden and 

epidemiology of RSV, reviewed the US RSV surveillance systems and definitions of RSV 

infection and disease, and began to discuss potential components of cost-effectiveness

considerations for RSV vaccines and monoclonal products. Upcoming activities will be to review 

the safety and efficacy with manufacturers of the developing vaccines and monoclonal 

antibodies, review RSV seasonality data in relation to potential recommendations for timing of 

administration of either of these types of products, review the results of cost-effectiveness 

models, present the data to the ACIP, and apply EtR Framework for each product. The first vote 

by ACIP is not expected until 2023.

Discussion Summary

Dr. Chen emphasized that this would an exciting set of discussions for the future for an area 

that has long been hindered. He asked whether the WG has or would be discussing the unusual 

RSV surge that occurred during the past summer, what the epidemiology was during the

coldest parts of the seasons, and what was observed last year—recognizing that these are 

COVID-19 times. 

Dr. Long indicated that the WG had not discussed the potential reasons for this very aberrant 

season specifically. As far as their deliberations for use of products, the next 12 months will be 

very important in terms of assessing whether RSV revert back to its more typical epidemiology.

All of that will affect recommendations and will be very important in terms of if/how it coincides

with an RSV season.

PNEUMOCOCCAL VACCINE

Session Introduction

Katherine Poehling, MD, MPH (ACIP WG Chair) introduced the Pneumococcal session. The 

Pneumococcal Vaccines WG’s terms of reference are to: 1) review current data including 

efficacy, effectiveness, immunogenicity, epidemiology, and cost-effectiveness of pneumococcal 

vaccines and assess the strength of the evidence; 2) review current recommendations 

considering up-to-date evidence; and 3) revise or update recommendations for pneumococcal 

vaccine use as needed. As a reminder, ACIP voted on 2 recommendations for the use of 

PCV14/PCV20 during the October 2021 meeting as follows:
ACIP Meeting Summary January 12, 2022

43

Adults aged ≥65 years who have not previously received a pneumococcal conjugate 

vaccine or whose previous vaccination history is unknown should receive a dose of 

pneumococcal conjugate vaccine (either PCV20 or PCV15). When PCV15 is used, it 

should be followed by a dose of PPSV23.

Adults aged 19–64 years with certain underlying medical conditions or other risk factors* 

who have not previously received a pneumococcal conjugate vaccine or whose previous 

vaccination history is unknown should receive a dose of pneumococcal conjugate 

vaccine (either PCV20 or PCV15). When PCV15 is used, it should be followed by a dose 

of PPSV23.

*Alcoholism, chronic heart/liver/lung disease, diabetes, cigarette smoking, chronic renal failure, nephrotic syndrome, immunodeficiency, iatrogenic immunosuppression, generalized malignancy, 

human immunodeficiency virus infection, Hodgkin disease, leukemia, lymphoma, multiple myeloma, solid organ transplants, congenital or acquired asplenia, sickle cell disease, or other 

hemoglobinopathies, CSF leak, or cochlear implant.

Much of the WG’s current focus is on the anticipated licensure in children, with PCV15 licensure 

expected in the first or second quarter of 2022 and PCV20 licensure expected in the second or 

third quarter of 2023. 

Updates from the Pneumococcal Vaccines WG

Miwako Kobayashi, MD, MPH (CDC/NCIRD) pointed out that the language voted on during the 

October 2021 ACIP meeting that Dr. Poehling described focused on adults who have not 

previously received the pneumococcal conjugate vaccine or whose previous vaccination history 

is unknown. Additional clinical guidance the WG proposed that was not part of the vote included 

the following:

Clinical Guidance on the PCV15–PPSV23 Interval

 

• When PCV15 is used, the recommended interval between PCV15 and PPSV23 is ≥1 

year. A minimum interval of 8 weeks can be considered for adults with an 

immunocompromising condition*, cochlear implant, or cerebrospinal fluid leak to 

minimize the risk for IPD caused by serotypes unique to PPSV23 in these vulnerable 

groups.

*chronic renal failure, nephrotic syndrome, immunodeficiency, iatrogenic immunosuppression, generalized malignancy, human immunodeficiency virus infection, Hodgkin disease, leukemia, 

lymphoma, multiple myeloma, solid organ transplants, congenital or acquired asplenia, sickle cell disease, or other hemoglobinopathies, CSF leak, or cochlear implant

Clinical Guidance for Those Who Previously Received PPSV23 Only

• Adults who have only received PPSV23 may receive a pneumococcal conjugate 

vaccine (either PCV20 or PCV15) at least 1 year after their last PPSV23 dose.

Clinical Guidance for Those Who Previously Received PCV13 (with/without PPSV23)

• The WG is in favor of providing an opportunity to administer higher-valent PCVs to 

those who have already received PCV13 (with/without PPSV23).

• The incremental public health benefits of providing PCV15 or PCV20 to adults who 

have received PCV13 only or both PCV13 and PPSV23 have not been evaluated by 

the ACIP.
ACIP Meeting Summary January 12, 2022

44

• The MMWR Policy Note expected to be published on January 28, 2022 does not 

include a recommendation on PCV15/PCV20 use in adults who previously received 

PCV13 (with/without PPSV23). 

The WG plans to conduct an evaluation on higher-valent pneumococcal conjugate vaccines for 

adults who previously received PCV13 for consideration by the ACIP in the future. Therefore, 

the proposed language for clinical guidance for adults who receive PCV13 with or without 

PPSV23 is as follows: 

The incremental public health benefits of providing PCV15 or PCV20 to adults who have 

received PCV13 only or received both PCV13 and PPSV23 have not been evaluated. 

These adults should complete the previously recommended PPSV23 series.

The WG has started reviewing data on PCV15 use in children in anticipation of FDA licensure of 

PCV15 for children as early as April 2022 and PCV20 licensure anticipated in 2023. Currently, 

PCV13 is recommended for routine administration for all children <2 years of age, catch-up

vaccination for children aged <5 years of age who missed their recommended doses, and 

children aged 2-18 years for certain medical conditions in series with PPSV23.14

The proposed policy question being considered by the WG is, “Should PCV15 be recommended 

as an option for US children who are recommended to receive PCV13?” In the months leading 

to the vote, the Pneumococcal WG plans to review the immunogenicity and safety of PCV15 

use in children; the epidemiology of pneumococcal disease and vaccine-preventable disease 

burden for invasive pneumococcal disease (IPD) and non-IPD; and the expected public health

impact and cost-effectiveness of PCV15 use in terms of the estimated direct/indirect effects in 

children and the impact on health equity. The WG will use the GRADE and EtR Framework to 

summarize the evidence. During the February 2022 ACIP meeting, the WG plans to present 

data on pediatric pneumococcal disease epidemiology, findings from Phase 2 and 3 PCV15 

studies in children, and part of the EtR Framework and GRADE. During the June 2022 ACIP 

meeting, the WG plans to present a summary of the cost-effectiveness analysis and the 

remainder of the EtR Framework. An ACIP vote on recommendations for use of PCV15

in children is anticipated after expected licensure and when deemed appropriate by ACIP.

Discussion Summary

Dr. Kotton requested clarification about what would be included in the MMWR if there is no 

recommendation for people who previously had a conjugate vaccine. Clinicians are left with a lot 

of questions about whether they should/should not be giving the vaccine. 

Referring to Slide 13, Dr. Kobayashi indicated that because the WG had not had the opportunity 

to present data on use of the higher-valent conjugate vaccines to the ACIP yet for consideration 

for a vote, the language they are currently planning to include in the upcoming MMWR is:

Clinical Guidance for Those Who Previously Received PCV13 (with/without PPSV23)

The incremental public health benefits of providing PCV15 or PCV20 to the adults who 

have received PCV13 only or both PCV13 and PPSV23 have not been evaluated. These 

adults should complete the previously recommended PPSV23 series.

14 MMWR 2010 (59); RR-11; MMWR 2013 (62); 521–524 
ACIP Meeting Summary January 12, 2022

45

Dr. Poehling pointed out that it is important to review the history of how this occurred. The WG 

worked hard to simplify the pneumococcal recommendations, recognizing that simplified

recommendations would increase coverage and equity. They also worked hard to get a timely 

vote after the licensure. During the October 2021 ACIP meeting, it was mentioned by multiple 

persons and there was discussion about immunocompromised and elderly populations. At that 

time, these conversations were truncated and it was understood that the WG could fill in the 

gaps on some of these questions by including the information in Clinical Considerations. That 

ACIP meeting was jam-packed, the schedule was tight, and there were many votes. Following 

that meeting, the WG met and developed recommended Clinical Considerations. In the review 

process, it became clear that the vote language was more restricted than intended. The WG 

met on January 11, 2022 and unanimously felt that enabling access to newer pneumococcal

conjugate vaccines is important for immunocompromised, high-risk, and elderly populations and 

that the proposed language creates clinical barriers and decreases both access and equity. At 

the same time, the WG recognized there are many naïve persons who need this vaccine. 

Moving forward, the WG proposes to quickly identify and evaluate the available data and 

present this information to the ACIP to fill in this gap. She requested input on any specific data

that the WG should include in such a presentation.

Dr. Lee noted that there was a distinction in her mind between people who have received

PCV13 only. She approached this from a pediatric perspective in which clinicians have to think 

about the immunization schedules for immunocompromised persons in particular in terms of 

whether someone is due for PPSV23 and if they should receive a polysaccharide vaccine or a 

conjugate vaccine as the boost in that instance. That might be a different question than people 

who already have received PCV13 and PPSV23 and she asked whether the WG was thinking 

about those in the same or a different way.

Dr. Poehling indicated that the WG talked about all of those, but was told that they could not 

move forward with what was presented yet.

Dr. Goldman (ACP) said that speaking as an individual practice internist, he had several

concerns with the policy of not allowing for an additional pneumonia dosage of the new

conjugate vaccine for those who have been previously vaccinated for 3 reasons: 1) the best 

interest of the patient, 2) logistical issues, and 3) the confusion that this will create in messaging 

with the policy. As an internist and primary care physician (PCP), the most important patient is 

the one right in front of him. While public health and resource concerns are necessary, he is 

more interested in what is most beneficial to that patient. Many patients have received either 

PCV13 with/without PPSV23 and may have received them at such a significant interval in the 

past that they are aging into a category for an additional dosage or are facing imunosenescence 

and are left unprotected at an older age. This reinforces the need for repeat vaccination. He 

does not believe it is in the best interest of the patient not to offer them an additional conjugate 

vaccine that will allow for additional protection. This is a case in which the harms are minimal, 

the vaccine is safe and effective, and permissive or shared clinical decision-making is 

appropriate. Many health care systems and physicians may have chosen the path to give only 

PCV20 over the PCV15/23 combination. To suggest now that they have to go back to an 

additional dose of PCV23 may create the impossible tasks of acquiring and stocking multiple 

vaccines, and patients will not be able to get fully protected. It is similar to when ACIP decided 

to allow for Tdap to be interchangeable with TD and allow only one vaccine to be able to be 

stocked. The previous confusion created by multiple schedule changes with pneumonia made it 

difficult for frontline physicians to implement. The hope was that this new vaccine schedule 

would keep it simple and allow for better vaccine uptake. He encouraged the committee to allow 

for an additional dose of conjugate vaccine to those who have previously had PCV13
ACIP Meeting Summary January 12, 2022

46

with/without PPSV23, with either a permissive recommendation or a shared clinical decisionmaking recommendation. He believes this will allow for improved protection against pneumonia, 

reduce the individual risk of disease, and save lives.

Dr. Long said that considering the unanimous wish of the WG that this not be put in the MMWR

and Dr. Poehling’s statement that she is willing to do the hard work to try to bring this to the 

ACIP in a little over a month’s time, she favored not including a statement at all about this 

situation of those who are not previously naïve for one more month until ACIP is able to assess 

the data more carefully. They all felt that it was the wrong direction to continue these individuals 

on the PPSV23 route when there is PCV20. They have said those who are naïve could receive 

either PCV15 or PCV20 and that if they got PCV15, it should be followed by PPSV23. She did 

not see how this was different from that, except that there would be nobody who could want to 

then give someone who had receive PCV13 PCV15 followed by PCV23. What would make the 

most sense and would restore the understanding and faith of practitioners in the pneumococcal 

vaccine recommendations would be to provide flexibility to use either PCV20 or PPSV23 in 

those who previously received PCV13. 

Dr. Kotton agreed with the comments from Drs. Goldman and Long and thought there should be 

flexibility and clarity. Already, the majority of clinicians she meets with do not understand the 

recommendations that were made years ago for PPSV23 and PCV13. When she brings up 

PCV15 and PCV20, they are further confused. There are data to suggest that there would not 

be harm in giving additional doses of conjugate vaccine. It is known from surveys and other 

sources that many Americans who are at high-risk for pneumococcal disease remain illprotected. The ACIP should not increase barriers toward providing protection, but rather should 

provide clinicians flexibility and significant clarity in the guidelines.

Dr. Fryhofer (AMA), speaking as a practicing physician, applauded the WG and ACIP for 

simplifying this pneumococcal recommendation, because there are now higher-valent conjugate 

vaccines. She thinks this will be much easier to implement and much easier to explain to those 

administering these vaccines. Previously, there were some groups of patients who would 

receive another dose of PPSV23 once they turned 65 years of age if it had been at least 5 years

since they had had a PPSV23. She requested clarification on whether there is no reason now 

for anyone to receive more than a single PPSV23 moving forward. 

Dr. Kobayashi confirmed this to be correct. Under the new recommendation, people who 

receive PCV15 are not recommended to receive repeated doses of polysaccharide vaccine at 

this point. However, this language refers those who received PCV13 to the existing 

recommendation. What that means is that if they are due for another polysaccharide vaccine, 

that is what they should get

Dr. Posner emphasized that recommendations must be based on the evidence reviewed. The 

issues people raised during this discussion highlighted the importance of moving quickly to 

review the evidence and appropriately consider any changes to the recommendations.

Dr. Zimmerman (APTR) speaking as an educator and practicing physician, agreed with Drs. 

Goldman and Long and emphasized that that intent of the WGs on which he has been 

privileged to serve for many years was simple recommendations and flexibility. He expressed 

his hope that this could be resolved quickly. 

Dr. Hogue (APhA) stressed that everything published that potentially could be changed again in 

February is going to create confusion no matter how clear and precise they think they are being. 
ACIP Meeting Summary January 12, 2022

47

He fully supported everything his colleagues said previously. Providers must be allowed

flexibility and there should be caution about putting anything in print that could lead to more 

confusion among practitioners and patients just a month later. He applauded ACIP’s 

simplification in the Fall meeting, which has been well-received. 

Dr. Loehr said that if he was understanding the position of several people, they were asking for 

flexibility to give PCV20 to someone who has had PCV13 alone or PCV13 plus PPSV23 in the 

past. They also would like to have this decision made quickly. Based on the timeline Drs. 

Poehling and Kobayashi outlined, there would not be an ACIP vote until June 2022. While he 

appreciated Dr. Goldman’s strong recommendation to provide flexibility, he was not comfortable 

making that kind of decision without data.

PUBLIC COMMENT

Ms. Katherine Falk

Parent and Vaccine Advocate

I’m Katherine Falk, a parent and vaccine advocate in Oakland, California. I thank the Committee 

again for all your hard work, including am absolutely crazy number of meetings. I first wanted to 

reiterate Dr. Stanley Plotkin’s January 4 written comment on the importance of the flu vaccine.

In this time of epidemic Omicron COVID, it is important that people be vaccinated against

influenza so that they do not need to seek medical care, which is in short supply. Moreover,

influenza itself can kill and disable. There has also been a lot of talk about comorbidities lately.

A person can live with a comorbidity for a long time only to be felled by a contagious illness,

whether it’s COVID, flu, pneumonia, or a combination. So, I’m glad to see pneumococcal and 

influenza vaccines for older adults on the agenda. I’m also really excited to see RSV vaccines 

on the agenda. I know it’s a threat to older adults and people with compromised immunity, but I 

also think of this blog I used to follow—remember blogs?—called The Spohrs Are Multiplying.15

The family’s first child was born prematurely with compromised lungs and died before her

second birthday. In her short lifetime, she suffered many illnesses, including RSV. It is shocking

to me that a virus that causes so much misery still has no vaccine, and I’m sure hoping that’s 

about to change. On a personal note, my 15-year-old daughter came down with COVID this

week. She got infected, likely at school, before we had time to get her a booster. If anyone

hearing this thinks it’s just a cold still, they’re going to get an earful from me. But as miserable 

as yesterday was, I was pleasantly surprised this morning to find that she’s feeling a bit better.

The vaccine didn’t prevent infection and maybe the booster would have if we’d had time, but 

those 2 doses she got last year do seem to be doing what they’re supposed to do—prevent the 

worst outcome. Thank you.

Joan Edelstein

Professor of Nursing and Faculty

School Nurse Credential Program

California State University, Sacramento

I’m Joan Edelstein, Professor of Nursing and Faculty in the School Nurse Credential Program

at California State University Sacramento. I’d like to thank the Committee for its tireless efforts

in expertly evaluating and transparently communicating the science behind all the Committee’s 

recommendations in spite of the many professional and political challenges during this

pandemic. We in public health have been concerned about a twindemic since 2020 and are now 

15 https://thespohrsaremultiplying.com/ 
ACIP Meeting Summary January 12, 2022

48

facing what is referred to as “flurona.” Primary prevention is always critical to an effective public 

health strategy. School-located vaccine clinics, for which school nurses are key partners

and leaders, should be a priority for the CDC, which recommends influenza school-located 

vaccine clinics on its website. The National Association of City and County Local Health Officers

(NACCHO) has a wealth of information on their website. They know that private medical sectors 

as well as public health clinics have limited capacity and are often unable to vaccinate the 

expanded population to the degree that school-located vaccine programs are. That is especially 

true in this pandemic. The advantages of doing this include an increased number of vaccinated 

children; improved efficiency and cost-saving from a public health perspective; increased 

access to students who are from minority families, minority groups, the economically 

disadvantaged, and families whose primary language is not English; reduced absenteeism for 

both vaccinated and unvaccinated students; and reduced absenteeism for staff and teachers.

The National Association of School Nurses (NASN) notes that reaching high vaccination 

coverage of school-aged children and their families, as outlined in Healthy People 2020 and 

2030, is an important public health objective. School nurses are in a critical position to create 

awareness, influence action, and provide leadership in the development of school-located 

vaccine programs, according to NASN. School nurses are trusted professionals within the 

school and community settings and can play a pivotal role in the success of these clinics, which 

historically have been shown to enhance vaccination rates and are one reason vaccination

against polio was so effective. These statements are all supported by data. Both flu and COVID 

vaccines can be given in the same school clinics to students, staff, families, and community. 

The CDC should include in their recommendations that school nurses be actively included in 

assessment planning, policy/program development, implementation, and evaluation of both 

vaccine programs and mitigation efforts. Rather than continuing to ignore these traditionally 

female school nurse positions, the CDC should take the lead in recognizing the importance of 

including school nurses in vaccine campaigns and enjoining state, county, and city health 

departments to partner with school nurses at the county, district, and school levels to carry out 

this critical task of getting our public health population vaccinated. I thank you so much for the 

time and the opportunity to speak.

Ms. Elizabeth Ditz

Vaccinate California

Good afternoon Committee members and thank you for your tireless service, which I deeply 

appreciate. My name is Liz Ditz and I live in San Mateo County, California. I’m speaking for 

myself, but I am a donor to Voices For Vaccines, which is a grassroots parent organization

advocating for high vaccine uptake. I’m also involved with a very large Facebook group,

Vaccine Talk, an evidence-based discussion forum that has nearly 80,000 members worldwide;

and the Redwood City Woman’s Club with over 100 members, most over 65. I am the COVID19 Committee Chair for the last group. I have data on flu vaccine uptake in the Women’s Club.

Since I started talking about COVID via email in March 2020, more of our members reported

going to get their flu vaccines in the fall of ‘20 and ‘21. Nagging works in this setting. With

respect to the pneumococcal vaccine changes, I have a primary care provider who is a family 

medicine doctor. However, I get my flu vaccine and the Moderna booster at my local big box 

grocery store that has a pharmacy because it’s more convenient—walking distance as opposed 

to a 30-minute drive. The rub is I have to inform my primary care provider with the vaccine

records from the big box store. Is there no easier way to do this? The developing pneumococcal 

recommendations will be of interest to both the Facebook group and my women’s group. One 

thing that has been a consistent pattern in both Vaccine Talk and the Women’s Club is how 

confusing they have found the messaging about vaccine recommendations. This committee has 

nothing to do with non-pharmaceutical interventions, so I won’t go there. But in that area, too, 
ACIP Meeting Summary January 12, 2022

49

government messaging has been very confusing. As a panel discussion showed, the new 

pneumococcal vaccine recommendations are confusing even to experts. As the workgroup 

continues to develop recommendations, may I suggest they also consider very carefully the 

messaging around who should get which vaccine and when? This is an area where expert 

advice from science communicators and public communications experts would be extremely 

valuable. These are two groups that have been underused since March 2020. Thank you again 

for all your hard work.

Good afternoon. My name is Kathy Cameron. I’m a pharmacist, public health professional, and 

Senior Director of the Center for Healthy Aging at the National Council on Aging, or NCOA. I 

appreciate the opportunity to provide comments today on behalf of NCOA, older adults, their 

family members, and caregivers. NCOA is a respected national leader and trusted partner to 

help people aged 60-plus live with health and financial security. We believe every person

deserves to age well. Vaccines are a vital part of aging well, and NCOA is committed to 

ensuring access for older adults and caregivers using public benefits. We also provide accurate 

and timely information about vaccines to our constituents. We recognize and commend the 

tremendous workload that ACIP has taken during the past 3 years, and we thank you for your 

dedication. I would like to address the issue of expanding access to pneumococcal vaccinations 

for as many Americans as possible, building on your previous discussions today. Last fall, we

were disappointed when despite strong arguments from some voting members, the Committee 

chose to limit access to newly FDA-approved vaccines to combat additional strains of 

pneumococcal disease to those 65 years and older and those with pre-existing conditions aged 

19 to 64. Widening the availability of these pneumococcal vaccines to those 50 and older would 

give a needed boost to the fight against yet another respiratory disease. We hope that ACIP will 

consider lowering the recommendation to adults 50 and older, many who are family caregivers 

themselves or work in healthcare and social service settings with older adults. CDC data shows 

that these new vaccines have the potential to save lives, are cost-effective, and could positively 

address health disparities. Existing vaccines cover roughly 40 of the approximately 90 strains of 

serotypes of pneumococcal disease. The new vaccines will increase the number of strains

covered and offer greater protection, particularly for older Americans and those with chronic 

conditions that put them at greater risk for contracting pneumococcal disease. Many Americans 

have fallen behind on routine vaccinations throughout the pandemic, and we must do all we can 

to help fix this problem. Offering clear-cut, prompt, and simple recommendations on

pneumococcal vaccines is imperative to staving off another wave of respiratory illnesses that 

could further tax not only an individual’s personal health, but our wider healthcare system. We 

urge ACIP to issue the recommendation guidance for the newly approved pneumococcal 

vaccinations as soon as possible as our nation continues to battle respiratory illnesses at a rate 

never seen. Strong and clear-cut recommendations from the CDC are critical each year, but

more so this flu and pneumonia season as experts are predicting it could be more serious than 

last year. Thank you again for the opportunity to provide comments.

Ms. Kathleen Cameron

Pharmacist & Public Health Professional

Senior Director, Healthy Aging

National Council on Aging
ACIP Meeting Summary January 12, 2022

50

Ms. Lindsay Clarke, JD

Senior Vice President

Health Education and Advocacy

Alliance for Aging Research

Good afternoon. I’m Lindsay Clark, Senior Vice President of Health Education and Advocacy at 

the Alliance for Aging Research. The Alliance is a leading nonprofit organization dedicated to 

accelerating the pace of scientific discoveries and their application to improve the experience

of aging and health. Today’s agenda includes many issues of importance to older adults, and 

we urge the Committee to consider the following as you continue your discussions. First, we 

applaud the Committee’s October recommendation for pneumonia vaccines. The simplifying 

and streamlining of the recommendations should help to eliminate confusion and improve 

uptake of the vaccines. To that point, while the Alliance strongly supports high-quality shared 

decision-making. We feel that the shared decision-making recommendations for the pneumonia 

vaccines are overly complex and we’re concerned that they could pose a barrier to care or could 

become a check-the-box activity. Standards for shared decision-making should offer patients

and providers understandable information about trade-offs among treatment options and 

facilitate the incorporation of patient preferences and values into the medical plan. Additionally, 

streamlined recommendations should aim to provide more definitive guidance for clinicians

based on the patient’s health status and access to care. Second, we urge the Committee to 

explicitly encourage older adults to receive high dose or adjuvanted influenza vaccines when 

available. The 2020-2021 recommendations avoid recommending enhanced influenza products 

over the standard dose flu shots for adults aged 65 and older despite evidence of superior 

efficacy. The recommendations should encourage older adults to seek out enhanced vaccines 

to better protect their health, particularly amid the continuing COVID-19 pandemic and the 

disease’s disproportionate impact on the aging population. While we acknowledge that any 

influenza vaccination is better than no influenza vaccination, ACIP recommendations should 

make a stronger statement in favor of enhanced vaccines for older adults. Finally, the Alliance is 

encouraged by the significant vaccine clinical development for RSV and older adults, and we’re 

glad to see the Committee tackling this important topic. While many people often discuss RSV 

in terms of impacts on the pediatric population, RSV is also recognized as a significant concern 

for older adults. Older adults are at greater risk for serious complications from the disease due 

to weakened immune system, and RSV can be especially life threatening for those with chronic 

heart or lung disease. Each year, more than 177,000 older adults are hospitalized and 14,000 

die from the infection. Beginning this important discussion in advance of any new product

approvals establishes an important foundation for timely recommendations, as well as builds 

awareness and consensus about the need to protect older adults from RSV. Thank you so 

much for the time and opportunity to comment.

Dr. Kelly Moore, MD, MPH

Chief Executive Officer

Immunize.org

Good afternoon. I'm Dr. Kelly Moore, CEO of immunized.org, a nonprofit supporting frontline 

vaccinators and immunization coalitions through educational resources and advocacy. I’m also 

a former member of the ACIP. First, thank you to everyone involved with ACIP for the quality of 

this transparent, evidence-informed policymaking process. Today I’d like to offer a few thoughts

about preferential recommendations. I believe the public’s health and public confidence in 

vaccination improves when the ACIP makes justifiable preferential recommendations based on 

solid evidence of distinctly superior performance and they are diminished when clear 
ACIP Meeting Summary January 12, 2022

51

distinctions are disregarded. The exact threshold for justifying a preference depends on the 

specific disease and vaccines and questions, and I’m not getting into that here. Well-informed 

members may reach different conclusions about what is justified depending on their values and 

points of view. But the concerns I often hear from those who are reluctant ever to express a 

preference include: What if we express a preference that there isn’t enough supply for 

everyone? Will it look bad if something unexpected happens later and we must change our 

policy? What if we express a preference that financially disadvantages another manufacturer 

and can lead to the discontinuation of a non-preferred product? For what it’s worth, here’s a bit 

of my own thinking about these concerns and the ultimate importance of expressing preferences 

when justified. First, the ACIP must consider supply and implementation issues, but I believe the 

highest priority is for ACIP to make the best recommendations for the health outcomes of 

vaccine recipients. Within reason, initial supply is less critical than making it clear what is 

preferred if it’s available and how to prioritize if necessary. This gives purchasing organizations, 

busy clinicians, and vaccine recipients clarity. As a “chicken and egg issue,” supply and access 

are issues most likely to resolve as a consequence of preference, not ahead of it. When the 

ACIP acts on the best available evidence, but unforeseen circumstances necessitate a later 

change, as we’ve done before, that’s not a flaw of the ACIP. It’s a feature. Judge the evidence 

and don’t let speculative what ifs result in decision paralysis. Finally, when ACIP prioritizes 

vaccines that produce substantially better health outcomes, that incentivizes vaccine innovation

to further improve vaccine effectiveness. It’s hard to justify innovation and effectiveness 

research if vaccines with widely disparate performance are consistently treated equally from a 

policy standpoint. It’s my hope that when questions of preference arise, ACIP and CDC will be 

willing to appropriately acknowledge significant advances in ways that encourage the further 

pursuit of superior vaccines in the best interest of the public’s health. Thank you.

Mr. Mark Gibbons

President/CEO

RetireSafe

Good afternoon. This is Mark Gibbons. I’m the President/CEO of Retire Safe. Retire Safe is an 

advocacy organization which endeavors to give voice to the multifaceted concerns of middle 

age and older adults. Needless to say, healthcare issues constantly top that list, particularly the 

last 2 years when the pandemic has dominated the conduct of all of our lives. Thanks to the 

spectacular work of researchers and scientists from the public and private sectors, though we 

are in a challenging fight, we have effective tools at hand to treat, combat, and advance 

prevention of COVID. We absolutely cannot step away from this effort and we must also

continue research so as to be ready for any future variants. But it is equally urgent that we 

continue to battle diseases that before COVID were taking a huge toll in suffering and loss of 

life, such as pneumonia, RSV, and influenza. It was in 2018 when 64% of the adults 65 and 

older had received a pneumonia vaccine—a promising increase from only 48% in 2000.

However, considering that about 1 in 20 people who contract pneumonia will die, that 

percentage is not nearly high enough. We also know that many Americans have fallen behind

on routine vaccinations throughout the pandemic, a trend we must work to reverse. Again, 

thanks to the advancements in science and the commitment of this Committee, older Americans

and those deemed at risk will have access to powerful, new innovative vaccines to protect

against pneumonia. It is our belief that broad coverage for those most vulnerable communities 

will have the greatest impact against this deadly disease. While we would have liked to see 

eligibility extended to those aged 50 and older, we urge broader access for Americans 16 to 64 

with serious adverse conditions. By offering clear, simple, and broad clinical guidance on who 

should receive the new pneumonia vaccines and when they should get them, providers will be 

able to make better recommendations for their patients. Then more eligible Americans will be 
ACIP Meeting Summary January 12, 2022

52

empowered to take this important step to protect their health. As we continue to face the 

ongoing threat of COVID-19 coupled with the flu and pneumonia season, all Americans who are 

eligible for the new pneumonia vaccines deserve access as soon as possible. We are grateful 

for this Committee’s ongoing efforts to protect all Americans—especially its elders. We do hope 

the Committee will, in the future, consider lowering the recommendation to adults aged 50 and 

older. For our part, we will continue to educate and inform our communities in important steps

that we can take to protect ourselves. Thank you for your time.
ACIP Meeting Summary January 12, 2022

53

CERTIFICATION

Upon reviewing the foregoing version of the January 12, 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 January 12, 2022

54

ACIP MEMBERSHIP ROSTER 

CHAIR 

LEE, Grace M, MD, MPH 

Associate Chief Medical Officer for Practice Innovation 

Lucile Packard Children’s Hospital 

Professor of Pediatrics, Stanford University School of Medicine 

Stanford, CA 

Term: 8/4/2021 – 6/30/2023

EXECUTIVE SECRETARY 

WHARTON, Melinda, MD, MPH

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention

Atlanta, GA

MEMBERS 

AULT, Kevin A, MD, FACOG, FIDSA 

Professor and Division Director 

Department of Obstetrics and Gynecology University of 

Kansas Medical Center 

Kansas City, KS 

Term: 10/26/2018 – 6/30/2022 

BAHTA, Lynn, RN, MPH, CPH 

Immunization Program Clinical Consultant 

Infectious Disease, Epidemiology, Prevention & Control Division 

Minnesota Department of Health 

Saint Paul, Minnesota 

Term: 7/1/2019 – 6/30/2023

BELL, Beth P, MD, MPH 

Clinical Professor 

Department of Global Health, School of Public Health 

University of Washington 

Seattle, WA 

Term: 7/1/2019 – 6/30/2023 

BROOKS, Oliver, MD, FAAP

Chief Medical Officer

Watts HealthCare Corporation

Los Angeles, CA

Past President, National Medical Association

Term: 7/26/2021 – 6/30/2025
ACIP Meeting Summary January 12, 2022

55

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 January 12, 2022

56

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 January 12, 2022

57

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 January 12, 2022

58

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 January 12, 2022

59

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 January 12, 2022

60

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 January 12, 2022

61

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 January 12, 2022

62

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 January 12, 2022

63

ACRONYMS USED IN THIS DOCUMENT

 

AAFP American Academy of Family Physicians 

AAP American Academy of Pediatrics

ABCs Active Bacterial Core Surveillance 

ACHA American College Health Association 

ACIP Advisory Committee on Immunization Practices

ACOG American College of Obstetricians and Gynecologists

ACP American College of Physicians 

aIIV Adjuvanted Influenza Vaccine 

AE Adverse Event

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 

APhA American Pharmacists Association 

ASTHO Association of State and Territorial Health Officers 

BLA Biologics License Application 

CDC Centers for Disease Control and Prevention

CMS Center for Medicare and Medicaid Services

COI Conflict of Interest 

CPCSSN Canadian Primary Care Sentinel Surveillance Network 

CPT® Current Procedural Terminology 

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

ED Emergency Department

ESRD End-Stage Renal Disease 

ET Eastern Time

EtR Evidence to Recommendation 

EVs Enhanced Vaccines 

FDA Food and Drug Administration

GBS Guillain-Barré Syndrome 

GMC Geometric Mean Concentration

GMR Geometric Mean Ratio 

GMT Geometric Mean Titers 

GRADE Grading of Recommendation Assessment, Development and Evaluation 

HAIVEN Hospitalized Adult Influenza Vaccine Effectiveness Network 

HCP Healthcare Personnel / Providers

HD-IV High-Dose Influenza Vaccine 

HHS (Department of) Health and Human Services

HIV Human Immunodeficiency Virus
ACIP Meeting Summary January 12, 2022

64

HRSA Health Resources and Services Administration 

ICD-9 International Classification of Diseases, Ninth Revision 

IDSA Infectious Disease Society of America 

IHS Indian Health Service 

ILI Influenza-Like Illness 

I-MOVE Influenza Monitoring Vaccine Effectiveness 

IPD Invasive Pneumococcal Disease 

MAAE Medically-Attended Adverse Events

MASO Management Analysis and Services Office 

MMWR Morbidity and Mortality Weekly Report

NACCHO National Association of County and City Health Officials 

NACI National Advisory Committee on Immunization Canada

NAPNAP National Association of Pediatric Nurse Practitioners 

NASN National Association of School Nurses 

NCEZID National Center for Emerging and Zoonotic Infectious Diseases 

NCIRD National Center for Immunization and Respiratory Diseases 

NCOA National Council on Aging 

NFID National Foundation for Infectious Diseases 

NIH National Institutes of Health

NMA National Medical Association 

NTTO National Travel and Tourism Office 

OIDP Office of Infectious Disease and HIV/AIDS Policy (OIDP)

PCP Primary Care Provider/Practitioner

PCR Polymerase Chain Reaction

PHAC Public Health Agency Canada 

PICO Population, Intervention, Comparison, Outcomes

PIDS Pediatric Infectious Disease Society 

rVE Relative Vaccine Efficacy

RCT Randomized Controlled Trial

RIV Recombinant Influenza Vaccine 

RSV Respiratory Syncytial Virus 

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 

TBE Tickborne Encephalitis 

US United States

USG United States Government

VE Vaccine Efficacy

VE Vaccine Effectiveness

VFC Vaccines For Children 

WG Work Group

WHO World Health Organization