DEPARTMENT OF HEALTH AND HUMAN 

SERVICES CENTERS FOR DISEASE CONTROL AND 

PREVENTION

Advisory Committee on 

Immunization Practices (ACIP)

Summary Report

February 28-March 1, 2021

Atlanta, Georgia 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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Table of Contents Page

Purpose 3

Acronyms 4-6

February 28, 2021

Welcome and Introductions 7-8

Coronavirus Disease 2019 (COVID-19) Vaccines

⬧ Introduction

⬧ FDA VRBPAC Meeting Summary

⬧ Overview of Janssen’s Single Dose COVID-19 Vaccine, Ad26.COV2.S

⬧ GRADE: Janssen COVID-19 Vaccine

⬧ Evidence to Recommendation Framework: Janssen COVID-19 Vaccine

⬧ Public Comment

⬧ Vote: Janssen COVID-19 Vaccine

8-51

 March 1, 2021

Coronavirus Disease 2019 (COVID-19) Vaccines

⬧ Introduction

⬧ Coronavirus Disease 2019 (COVID-19) Vaccines

⬧ Implementation Considerations for COVID-19 Vaccines

⬧ Clinical Considerations for Use of COVID-19 Vaccines

⬧ Vaccine Safety Technical Subgroup (VaST) Introduction

⬧ COVID-19 Vaccine Safety Update

⬧ VaST Assessment of Safety Data

⬧ Implementation Considerations for COVID-19 Vaccines

51-91

Certification 92

Membership Roster 93-101
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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US DEPARTMENT OF HEALTH AND HUMAN SERVICES 

CENTERS FOR DISEASE CONTROL AND PREVENTION

National Center for Immunization and Respiratory Diseases 

Advisory Committee on Immunization Practices (ACIP) 

Virtual Meeting 

February 28-March 1, 2021

Statement of Purpose 

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

Control and Prevention (CDC), National Center for Immunization and Respiratory Diseases

(NCIRD) convened a virtual meeting of the Advisory Committee on Immunization Practices 

(ACIP). The meeting was held on February 28-March 1, 2021 beginning at 11:00 am Eastern 

Standard Time (EST).

The ACIP is formally chartered under the Federal Advisory Committee Act (FACA) to provide 

advice and recommendations to the HHS Secretary, HHS Assistant Secretary for Health, and 

the CDC Director regarding use of vaccines and related agents for effective control of vaccinepreventable diseases in the civilian population of the United States (US). Recommendations 

made by the ACIP are reviewed by the CDC Director, and if adopted, are published as official 

CDC/HHS recommendations in the Morbidity and Mortality Weekly Report (MMWR). The CDC 

Director informs the Secretary, HHS, and the Assistant Secretary for Health, of immunization 

recommendations. Upon the licensure of any vaccine or any new indication for a vaccine, the 

committee shall, as appropriate, consider the use of the vaccine at its next regularly scheduled 

meeting. If the committee does not make a recommendation at the committee’s first regularly 

scheduled meeting, the committee shall provide an update on the status of such committee’s 

review.

The purpose of the February 28-March 1, 2021 ACIP emergency meeting was to review the 

Food and Drug Administration (FDA) Emergency Use Authorization (EUA) of the Janssen 

COVID-19 vaccine for individuals 18 years of age and older and consider and discuss ACIP 

recommendation of this vaccine. In addition, the ACIP considered and discussed 

implementation and clinical considerations for use of COVID-19 vaccines, COVID-19 vaccine 

safety, and emerging SARS-CoV-2 variants. Information for the public to attend the virtual ACIP

meeting via webinar or teleconference was published in the Federal Register in accordance with 

FACA regulations and rules. All sessions of the meeting were open to the public (Attachment 1: 

Membership Roster).
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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Acronyms

AAFP American Academy of Family Physicians 

AAP American Academy of Pediatrics

ACHA American College Health Association 

ACIP Advisory Committee on Immunization Practices

ACOG American College of Obstetricians and Gynecologists

ACP American College of Physicians 

Ad.26 Adenovirus 26 

AE Adverse Event

AESI Adverse Events of Special Interest 

AGS American Geriatric Society 

AHIP America’s Health Insurance Plans

AI/AN American Indian/Alaskan Native 

AIM Association of Immunization Managers 

AMA American Medical Association

AOA American Osteopathic Association 

APC Antigen-Presenting Cells 

APhA American Pharmacists Association 

APTR Association for Prevention Teaching and Research

ASTHO Association of State and Territorial Health Officers 

ATSDR Agency for Toxic Substances and Disease Registry

BARDA Biomedical Advanced Research and Development Authority 

BLA Biologics Licensure Application 

BMI Body Mass Index

CBER Center for Biologics Evaluation and Research 

CDC Centers for Disease Control and Prevention

CISA Clinical Immunization Safety Assessment 

CMS Center for Medicare and Medicaid Services

CNS Central Nervous System 

COI Conflict of Interest 

COVID-19 Coronavirus Disease 2019 

CSTE Council of State and Territorial Epidemiologists 

DART Developmental and Reproductive Toxicity 

DNA Deoxyribonucleic Acid 

DoD Department of Defense

DRC Democratic Republic of the Congo 

DSMB Data Safety Monitoring Board 

DVA Department of Veterans Affairs

DVT Deep Vein Thrombosis 

EHR Electronic Health Record 

EtR Evidence to Recommendation

EUA Emergency Use Authorization 

FAS Full Analysis Set 

FDA Food and Drug Administration

FEMA Federal Emergency Management Agency

FIH First in Human 

GBS Guillain-Barré Syndrome

GMT Geometric Mean Titers 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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GRADE Grading of Recommendation Assessment, Development, and Evaluation

HCP Health Care Personnel / Providers

HCW Health Care Workers 

HHS (Department of) Health and Human Services

HRSA Health Resources and Services Administration 

ICU Intensive Care Unit 

IDSA Infectious Disease Society of America 

IHS Indian Health Service 

IM Intramuscular 

ISO Immunization Safety Office

ISTM International Society for Travel Medicine 

JAMA Journal of the American Medical Association 

KFF Kaiser Family Foundation 

KPCO Kaiser Permanente Colorado 

LAIV Live Attenuated Influenza Vaccine 

LTCF Long-Term Care Facilities 

MAAE Medically-Attended Adverse Event

MedDRA Medical Dictionary for Regulatory Activities 

MIS-C Multisystem Inflammatory Syndrome in Children 

MMWR Morbidity and Mortality Weekly Report

mRNA Messenger Ribonucleic Acid 

NACCHO National Association of County and City Health Officials 

NACI National Advisory Committee on Immunization Canada

NAPNAP National Association of Pediatric Nurse Practitioners 

NCEZID National Center for Emerging and Zoonotic Infectious Diseases 

NCHHSTP National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention 

NCHS National Center of Health Statistics 

NCIRD National Center for Immunization and Respiratory Diseases 

NFID National Foundation for Infectious Diseases 

NGA National Governors Association 

NHP Non-Human Primates 

NHSN National Healthcare Safety Network 

NIAID National Institute of Allergy and Infectious Diseases 

NIH National Institutes of Health

NMA National Medical Association 

NPI Non-Pharmaceutical Intervention

NS3 National SARS-CoV-2 Strain Surveillance 

NVAC National Vaccine Advisory Committee 

OID Office of Infectious Disease 

OIDP Office of Infectious Disease Policy and HIV/AIDS 

PCP Primary Care Physician 

PCR Polymerase Chain Reaction 

PEG Polyethylene Glycol 

PHAC Public Health Agency Canada 

PhRMA® Pharmaceutical Research and Manufacturers of America®

PI Principal Investigator

PICO Population, Intervention, Comparison, Outcomes

PIDS Pediatric Infectious Disease Society 

PP Protocol Population 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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PPE Personal Protective Equipment 

PreVAIL kIds Predicting Viral-Associated Inflammatory Disease Severity in Children with 

Laboratory Diagnostics and Artificial Intelligence 

PRISM Pediatric Research Immune Network on SARS-CoV-2 and MIS-C 

PT Preferred Terms (MedDRA)

RBD Receptor-Binding Domain 

RCA Rapid Cycle Analysis

RCT Randomized Controlled Trial

RR Relative Risk

RSV Respiratory Syncytial Virus 

RT-PCR Reverse Transcriptase Polymerase Chain Reaction

SAE Serious Adverse Event 

SAHM Society for Adolescent Health and Medicine 

SARS Severe Acute Respiratory Syndrome 

SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus-2 

SGTF S-Gene Target Failure 

SHEA Society for Healthcare Epidemiology of America 

SIG SARS-CoV-2 Interagency Group 

SMEs Subject Matter Experts

SNF Skilled Nursing Facilities 

SPHERES

Consortium

SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology 

and Surveillance Consortium

SVI Social Vulnerability Index 

UK United Kingdom

US United States

USDA US Department of Agriculture 

USG US Government 

USPHS US Public Health Service 

VA (US Department of) Veteran’s Affairs 

VA ADERS VA Adverse Drug Event Reporting System 

VAED Vaccine-Associated Enhanced Disease 

VAERS Vaccine Adverse Event Reporting System

VaST ACIP COVID-19 Vaccine Safety Technical Subgroup 

VE Vaccine Efficacy

VE Vaccine Effectiveness

VRBPAC Vaccines and Related Biological Products Advisory Committee Meeting 

US United States

USG United States Government

VSD Vaccine Safety Datalink

VTEU Vaccine Treatment Evaluation Unit 

WG Work Group

WGS Whole Genome Sequencing 

WHO World Health Organization
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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Amanda Cohn, MD

Executive Secretary, ACIP/CDC

Rochelle P. Walensky, MD, MPH

Director, Centers for Disease Control and Prevention 

Administrator, Agency for Toxic Substances and Disease Registry

José Romero, MD, FAAP

ACIP Chair

Dr. Cohn officially called to order the February 28-March 1, 2021 emergency meeting of the 

Advisory Committee on Immunization Practices (ACIP). She indicated that the slides for the 

meeting could be accessed on the ACIP website at the following URL: 

https://www.cdc.gov/vaccines/acip/meetings/slides-2021-02-28-03-01.html

Additionally, the live webcast videos will be posted to the website following the meeting. Meeting 

minutes will be posted to the ACIP website generally within 90 to 120 days of the meeting. A 

short Executive Summary of the meeting will be posted within a week after the meeting.

Dr. Walensky welcomed and thanked the ACIP members, recognizing that the work they do is 

extraordinary and that the timing is not always ideal, during the daytime, or during work week 

hours. She acknowledged the many ACIP meetings that have been convened in the context of 

the COVID-19 pandemic, that the work has been hard and voluminous, and that the ACIP 

members have been making heavy and critical decisions. She indicated that she wanted to 

present as they embarked on this day with some very important decisions for the nation ahead 

of them, and to thank the members for the work they are doing. People are listening and 

engaged who really want to know what important information the ACIP wants to convey. From 

the bottom of her heart, she thanked them for their efforts. Dr. Cohn expressed appreciation for 

Dr. Walensky’s opening comments, which she knew was much appreciated by all of the 

members who have been truly extraordinary over the last year.

In terms of meeting logistics, participants were instructed to raise their hands virtually when Dr. 

Romero opened the floor for discussion and to disable their video or mute their phone lines to 

reduce issues with the Zoom connection. Dr. Cohn explained that during the discussion period, 

the order in which Dr. Romero would take questions would be first from ACIP Voting Members, 

second from Ex Officio and Liaison member representatives, and then from the audience. The 

plan was to stay on schedule with the meeting agenda as much as possible. 

The next regularly scheduled ACIP meetings will be convened on June 23-24, 2021 and 

October 20-21, 2021. Additional meetings are likely to be scheduled to evaluate and respond to 

COVID vaccine issues between the regularly scheduled meetings.

February 28-March 1, 2021: Welcome & Introductions
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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Dr. Cohn explained that there would be an oral public comment session before the vote at 2:15 

PM EST. Given that many 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 any other individuals wishing to make written public comments may submit them 

through https://www.regulations.gov using Docket Number CDC-2021-0021. Further information 

on the written public comment process can be found on the ACIP website.

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 conflict of interest (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. For all COVID vaccine votes, some members may be funded by the National 

Institutes of Health (NIH) to work on COVID vaccine clinical trials. Because they are working on 

products under investigations, they will be asked to recuse themselves from COVID vaccine 

votes. At the beginning of each meeting, ACIP members state any COIs.

As a reminder, ACIP membership nominations are open. Applications for membership are due 

not later than July 21, 2021 for a 4-year term beginning July 2022. Emails will be sent out 

through listservs to solicit nominations.

Dr. Romero conducted the roll call on both days of the meeting. One COI was declared for this 

meeting by Dr. Chen, who reported that he was involved in clinical studies of COVID vaccines 

until October 2020. No other COIs were declared. A list of Members, Ex Officio Members, and 

Liaison Representatives is included in the appendixes at the end of the full minutes for the 

February 28-March 1, 2021 ACIP meeting.

Dr. Cohn announced on the second day of the meeting that Dr. Walensky, CDC Director, signed 

the Decision Memo approving ACIP’s recommendations for use of the Janssen vaccine. A 

Morbidity and Mortality Weekly Report (MMWR) was anticipated to be published on March 2, 

2021.

Introduction

Beth Bell, MD, MPH 

ACIP, COVID-19 Vaccine WG Chair

Clinical Professor, Department of Global Health

School of Public Health, University of Washington 

Dr. Bell introduced the session, first reflecting on the fact that this meeting marked almost 

exactly one year from the first COVID-19-associated death in the United States (US). Over the 

course of the past year, more than half a million people in this country have lost their lives to this 

virus. This is the 11th emergency meeting for the ACIP on COVID-19. During this time, ACIP has 

made recommendations for 2 vaccines that received Emergency Use Authorization (EUA) from 

Coronavirus Disease 2019 (COVID-19) Vaccines: February 28, 2021 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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the Food and Drug Administration (FDA). COVID cases and deaths are decreasing, but the 

pandemic is very far from over and there are still many challenges. The need for additional safe 

and effective vaccines remains urgent and vital to ending the pandemic.

During February, the COVID-19 WG continued to meet weekly. The topics covered during this 

month included an overview of adenovirus vector vaccines, the clinical development program for

the Janssen Ad26.COV.2.S COVID-19 vaccine, the GRADE (Grading of Recommendation 

Assessment, Development and Evaluation) and EtR (Evidence to Recommendations) 

Framework for the Janssen COVID-19 vaccine, considerations for the use of COVID-19 

vaccines, and safety updates.

The FDA issued an EUA for use of the Janssen COVID-19 vaccine on February 27, 2021 for the 

prevention of COVID-19 for individuals 18 years of age and older. Therefore, ACIP now needed 

to consider this third vaccine. With that in mind, the agenda for February 28, 2021 included the 

following topics:

❑ Overview of Janssen’s Single-Dose COVID-19 Vaccine: Ad26.COV2.S

❑ GRADE: Janssen COVID-19 Vaccine

❑ EtR Framework: Janssen COVID-19 Vaccine

❑ Public Comment

❑ Discussion 

❑ ACIP Vote: Janssen COVID-19 vaccine

Dr. Bell expressed gratitude to all of the ACIP COVID-19 WG members, liaisons, consultants, 

and CDC staff for all of their hard work and support in these efforts. 

VRBPAC Meeting Summary

Doran Fink, MD, PhD

Deputy Director

Division of Vaccines and Related Products Applications

Office of Vaccines Research and Review

Center for Biologics Evaluation and Research

Food and Drug Administration

Dr. Fink provided a summary of the Vaccines and Related Biological Products Advisory 

Committee (VRBPAC) meeting convened on February 26, 2021 to discuss Janssen’s request 

for an EUA for their COVID-19 vaccine. The meeting agenda opened with a presentation by the 

FDA to refresh VRBPAC on EUA and considerations specific to COVID-19 vaccines. 

Presentations also were heard from the CDC on the epidemiology of COVID-19 strain variants 

and post-marketing surveillance data from currently authorized COVID-19 vaccines, as well as a 

presentation from the FDA on plans for additional post-marketing surveillance. Following a 

public comment period, there were presentations on data from studies of the Janssen COVID19 vaccine that were made first by representatives of Janssen and then the FDA’s presentation 

of their comprehensive and independent review of the data submitted by Janssen in their EUA 

request. The meeting concluded with a discussion by the VRBPAC and a vote. The VRBPAC 

engaged in an in-depth discussion, following which they voted unanimously in favor of the 

determination that the known and potential benefits of the Janssen COVID-19 vaccine outweigh 

the known and potential risks in support of issuing an EUA for the vaccine.
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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Important questions were raised by some committee members, one of which pertained to the 

case definition for “moderate to severe” COVID-19 used by Janssen in their clinical trials in that 

it was all-encompassing of symptomatic disease and there were many cases in the trial that fell 

outside of that case definition. However, the FDA raised the point that the authorized indications 

for the COVID-19 vaccines for Janssen would be the same as for those previously authorized 

for Pfizer and Moderna for the prevention of COVID-19 due to SARS-CoV-2 without any 

specification of severity of disease. The committee also inquired about currently ongoing studies 

being conducted by Janssen evaluating a 2-dose regimen of their COVID-19 vaccine and asked 

what would happen if data from that study indicated that a 2-dose regimen was potentially more 

effective or offered greater benefit than the single-dose regimen for which the EUA was 

requested. The FDA advised the committee that if new data were to come to light supporting a 

2-dose regimen, there are regulatory options either through a revision of the EUA or under a 

Biologics Licensure Application (BLA) to support the use of a 2-dose regimen of the vaccine. 

The committee also inquired about ongoing studies to evaluate the effectiveness of the vaccine 

against asymptomatic infection and transmission. These studies are ongoing for the Janssen, 

Pfizer, and Moderna COVID-19 vaccines. Data should be available at the time BLAs are 

submitted if not before. The committee was very interested in further development of COVID-19 

vaccines for use in pediatric populations. Those studies are either ongoing or expected to begin 

eminently. Finally, the FDA asked the committee to opine on efficacy in subgroups in the clinical 

trials specifically in adults 60 years of age and older with comorbidities. The committee 

members did not express serious concerns about vaccine efficacy in that population specifically, 

and generally were in agreement with the conclusions of Janssen and the FDA that the vaccine 

is highly effective against COVID-19-associated hospitalization and deaths and that apparent 

differences in vaccine efficacy estimates between certain subgroups are likely the result of 

smaller numbers of cases in those subgroups, leading to imprecision in the estimates.

In terms of the unanimous recommendation in favor of the EUA, VRBPAC members felt it was 

important to make sure that the public understands that this vaccine appears to be highly 

effective for all populations for prevention of COVID-19-related hospitalizations and deaths, and

that it also is important not to compare this vaccine with other authorized vaccines because they 

have not been compared head-to-head and were evaluated at different times under different 

conditions.

Overview: Janssen’s Single-Dose COVID-19 Vaccine, Ad26.COV2.S

Macaya Douoguih, MD, MPH

Head of Clinical Development and Medical Affairs

Janssen Pharmaceuticals Companies of Johnson & Johnson

Dr. Douoguih thanked the ACIP for the opportunity to present data from Janssen’s development 

program as they seek ACIP’s recommendation for how the Janssen COVID-19 vaccination will 

be used in communities across the country. While few FDA-authorized COVID-19 vaccines are 

already being distributed, there remains an urgent need for effective and safe vaccines in order 

to vaccinate a majority of the US population, ensure protection against severe disease, and 

subsequently reduce the burden on the healthcare system. Now that the FDA has authorized 

the Janssen COVID-19 vaccine candidate (Ad26.COV2.S) for emergency use with an indication 

to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and above, the 

vaccine will be able to play a critical role in the global fight on COVID-19.
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Ad26.COV2.S was studied in a large Phase 3 study in which more than 44,000 participants 

were enrolled. The study was conducted in multiple countries during the height of the pandemic. 

The vaccine offers substantial protection, especially against severe COVID-19 including 

hospitalization and death, irrespective of variants. It is well-tolerated and safe. It is a single-dose 

regimen with storage and transportation conditions that are compatible within existing 

distribution channels. Specifically, Janssen’s vaccine has demonstrated early onset of 

protection against symptomatic COVID-19. Particularly important in the context of a pandemic, 

Janssen has observed 85% vaccine efficacy against severe COVID-19 globally and in the US at 

least 28 days after vaccination. For the key secondary endpoints, the effect was consistent 

across geographic regions. There was equally high protection in South Africa where about 95% 

of the strains were the emerging variant of the B.1.351 lineage.

Importantly for the primary analysis, there were no COVID-19 related hospitalizations in the 

vaccine group versus 16 in the placebo group. There were no COVID-19 related deaths in the 

Ad26 group compared to 5 in the placebo group. In the US, the vaccine showed 72% vaccine 

efficacy at least 28 days after vaccination. There were more than 19,000 participants in the US 

and particular attention was paid to ensuring that a diverse population was recruited. The 

primary endpoint was achieved with 66% vaccine efficacy for moderate to severe/critical 

COVID-19 for the overall study population after Day 28 and protection was observed as early as 

2 weeks after vaccination. Consistent efficacy was seen across age, comorbidities, sex, race, 

and ethnicity.

These results are particularly important when considering when the vaccine was studied. The 

Janssen study sites were located in areas where COVID-19 incidence was highest and where 

variants were emerging (e.g., US, South Africa, and Brazil). Still, the vaccine efficacy against 

severe/critical COVID-19 was high. Based on sequencing of approximately 72% of COVID-19 

cases in the study, it is evident that the prevalence of new variants was close to 70% in Brazil 

and greater than 90% in South Africa. Of note, Janssen did not observe the P.1 strain in the 

Brazil site. These efficacy rates are based on the total dataset, including non-centrally 

polymerase chain reaction (PCR)-confirmed cases.

The last few months have demonstrated that it is critically important to manufacture and 

distribute vaccines quickly and efficiently. Janssen’s vaccine offers logistical and practical 

advantages to help simplify distribution and expand vaccine access. Each person receives a 

single injection of 0.5 ml. The application of a single-dose regimen offers the ability to vaccinate 

the population faster. Each vial contains 5 doses and no dilution is required. The vaccine can be 

stored for 3 months at normal refrigerator temperatures of 2° to 8° C (36° to 46° F) and has a 2-

year shelf life when frozen at -25° to -15° C (-13° to 5° F). Janssen has continuously improved 

its manufacturing and formulation processes. Now that Janssen has received an EUA from the 

FDA, they are poised to begin shipping and delivering enough single doses to vaccinate 20 

million Americans by the end of March. This is part of the overall commitment to supply 100 

million doses to the US Government (USG) in the first half of 2021. The vaccine can be easily 

shipped using the existing supply chain infrastructure.

In addition to these key features, Janssen has substantial clinical experience with more than 

193,000 people vaccinated with its Ad26-based vaccines. These studies were conducted across 

continents, including participants of various ages, races, and ethnicities and also included 

vaccination of pregnant and breastfeeding women within Janssen’s Ebola program. Janssen’s 

Ebola vaccine was licensed in Europe in July 2020 and is currently part of a mass vaccination 

program in Rwanda. Regular reviews of the safety database have shown overall good 

tolerability and safety. Local and systemic reactogenicity are in line with what has been 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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observed with other licensed vaccines. Database searches focused on adverse events of 

special interest (AESI) have not revealed any safety signals to date.

Regarding key studies in the comprehensive development program, Janssen has performed 

numerous animal studies including those in non-human primates (NHPs) to study vaccine 

immunogenicity and efficacy. A Phase 1/2a study, COV1001, was the first in human (FIH) study 

to examine safety, immunogenicity, and dose selection. A Phase 2 trial, COV2001, investigated 

a range of dosing regimens. An ongoing pivotal Phase 3 study, COV3001, is examining the 

efficacy, safety, and immunogenicity of a single-dose regimen. Data from this study were 

submitted to the FDA in support of Janssen’s application for emergency use.

The Janssen presentation during this ACIP session provided a readout of the ongoing 

COV3001 study. Since the initial analyses, additional information on cases observed has 

become available. This will help to address some of the questions that those results could have 

triggered. Janssen also has a series of planned studies. The efficacy of a 2-dose regimen is 

being evaluated in Study COV3009 for which it is estimated that results will be available later in 

2021. Several immunogenicity and safety studies will be conducted in children 0-17 years of 

age. The study in adolescents is anticipated to open the first week of March 2021. Janssen also 

anticipates starting a study in pregnant women in the second and third trimesters toward the 

end of March or Early April 2021. Studies also are planned to begin in immunocompromised 

individuals in the third quarter of 2021. Several post-authorization observational studies are also 

planned to assess vaccine safety and effectiveness in the real-world, which will include the 

development of a pregnancy exposure registry.

By design, the Janssen Ad26 vector cannot replicate in the human body. The E1 and E3 region 

are important in the development of Janssen’s vector vaccine. By deleting E1 from the 

adenovirus DNA genome, the virus irreversibly loses its ability to replicate in human cells. Most 

of the E3 genes have been deleted as well, which creates more room for the genome for a 

transgene that codes for the protein that triggers the desired immune response. For the 

production of replication incompetent viral vectors, the well-characterized PER.C6 cell line

complements for the missing E1 gene. The vector can replicate only in an E1 complementing 

cell line and cannot replicate in the human body. Of note, the PER.C6 cell line grows in a 

medium that is free of animal components. A vial of Janssen’s Ad26-based vaccine contains a 

buffer with commonly used ingredients in vaccines. There are no adjuvants, antibiotics, or

preservatives.

First, a single dose is injected into the muscle in order to deliver the transgene to a diversity of 

cells. The transgene encoded spike protein is then expressed on the surface of these cells. 

Innate immune responses triggered by the Ad26 vector provide the optimal microenvironment 

for the immune response against the spike protein. Attracted antigen-presenting cells (APCs) 

then pick up the spike protein and migrate to the lymph node, eliciting both humoral and cellular 

immune responses. The CD4+T helper cell responses are predominantly of the Th1 phenotype 

and stimulate B cells. Spike-specific antibodies are then produced by plasma cells. These 

antibodies have SARS-CoV-2 neutralizing antibodies and Fc-mediated antiviral effector 

functions that may place a key role in vaccine-elicited protective immunity, including protection 

against the new SARS-CoV-2 variants of concern. Spike-specific CD8+T cell responses are 

also triggered. CD8+T cell responses mature as cytotoxic effector cells with the ability to kill 

virus-infected cells. This is an important effector mechanism of vaccine-elicited antiviral 

immunity. The FDA guidelines classify adenoviral vectors as non-integrating, meaning that they 

do not have the propensity to modify the host genome.
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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In terms of preclinical data, a single dose of Ad26.COV2.S fully protects against SARS-CoV2 

challenge in NHP. Near complete protection was observed against viral replication in the nose 

and full protection in the lungs. This protective efficacy was durable for at least 6 months. Highlevel lung viremia was seen even after vaccination with a 4-fold lower dose in the face of lower 

antibody titers. In addition, a single dose also gave near complete protection against viral 

replication in the lungs of aged NHP. To complement the NHP study, Janssen tested its vaccine 

in Syrian golden hamsters where it also demonstrated protective efficacy. Histopathology in 

animals with low-level breakthrough infections demonstrated no evidence of vaccine-associated 

enhanced disease (VAED).

Overall, these results satisfied the FDA guidance criteria to allow for progression into the human 

clinical trials. Since Janssen had an opportunity to review the previous design and results of its 

Phase I/II trials with ACIP, Dr. Douoguih provided a highly-level summary as a reminder. 

Following a single dose of Ad26.COV2.S, neutralizing antibody titers were elicited in 96% of 

adults independent of age. Titers were detected as early as 14 days post-vaccination, which 

increased in the following weeks and was maintained thereafter. This was irrespective of the 

vaccine dose used. Both CD8+ and CD4+ T cell responses were observed. The Th1 dominance 

of the CD4+ T cell responses in combination with the neutralizing antibody response minimizes 

the risk for VAED. In addition, 2 doses were tested. While both had a favorable safety profile, 

the lower dose had a more favorable reactogenicity profile. Therefore, the lower Ad26.COV2.S 

vaccine does of 5x1010 viral particles was selected for the COV3001 Phase 3 study.

Regarding the results from the Phase 3 study known as ENSEMBLE, the primary analysis 

showed that the study met its primary endpoints, demonstrating the ability of a single dose of 

Ad26-COV2.S vaccine to protect against moderate and severe/critical COVID-19 in adults and 

that it has an acceptable safety and reactogenicity profile. COV3001 is a randomized, doubleblind, placebo-controlled Phase 3 trial that is evaluating the efficacy, safety, and immunogenicity 

of a single dose of Ad26-COV2.S vaccine. Participants were randomized 1:1 to receive an 

injection of either vaccine or saline placebo. Randomization was stratified by site, age, and the 

absence or presence of comorbidities. The first part of the study consisted of a safety run-in 

phase. Phase 1a of the safety run-in enrolled 2000 adults 18-59 years of age without 

comorbidities. Following a planned safety review, enrollment was permitted to progress to Stage 

1b to include participants up to 59 years of age with and without comorbidities. Stage 2a began 

in parallel to Stage 1a and enrolled 2000 adults ≥ 60 years of age without comorbidities. This 

cohort took somewhat longer to recruit. After a planned safety review in which the Data Safety 

Monitoring Board (DSMB) identified no safety concerns, the study progressed to Stage 2b to 

include adults ≥ 60 years with and without comorbidities. Given that those ≥ 60 years of age are 

at higher risk for severe COVID-19, the study targeted at least 30% of the total study population 

to be ≥ 60 years of age.

In terms of the co-primary endpoints, vaccine efficacy to prevent moderate to severe/critical 

COVID-19 with onset at least 14 days and at least 28 days after vaccination, the primary 

hypothesis is that the lower limit of the 95% confidence interval of the point estimate is > 30%. 

This had to be met for both co-primary endpoints in order to declare success. The case 

definitions for moderate COVID-19 and Severe/Critical COVID-19 was as follows:
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

14

 

Janssen has a blinded Clinical Severity Adjudication Committee to evaluate all severe cases, as 

well as moderate cases that have at least 3 signs or symptoms. Classification of a case of 

Severe/Critical by the adjudication committee was considered definitive.

With respect to disposition and efficacy results, a total of 44,325 participants were randomized 

of whom 43,783 received an injection of either Ad26.COV2.S or placebo. This makes up the Full 

Analysis Set (FAS) and is the safety population. The per Protocol Population (PP) is the primary 

efficacy population and includes all participants who were seronegative at the time of injection 

and had no other major protocol deviations judged to possibly affect vaccine efficacy. 

Participants also were excluded when they had a positive PCR test result on the day of 

injection. The PP at-risk set includes all participants in the PP population, but excludes those 

with a positive PCR test between injection through Day 14 or Day 28.

No relevant differences were observed between the 2 groups in terms of the overall 

demographics of the global population at baseline. Efforts were in place to reach pre-defined 

targets for subgroups and showed good representation in terms of age, race, ethnicity, and sex. 

Enrolling significant numbers of participants ≥ 60 years of age was important for evaluating 

vaccine efficacy, with a target of 30% for the global population. The Ad26.COV2.S group 

includes 7331 (33%) participants ≥ 60 years of age and the placebo group had 7341 (34%). 

Also of note is that 20% of the FAS were frontline or essential workers or healthcare 

professionals. The baseline demographics for just the US participants showed no relevant 

differences between groups. A similar portion of participants are ≥ 60 years of age with 3761

(39%) in the vaccine group and 3777 (39%) in the placebo group. More importantly, participants 

are representative of the US population in terms of race and ethnicity and are reflective of the 

diversity of the population.

Even though people with pre-existing comorbidities are at higher risk for developing severe 

COVID-19, it was important to enroll participants with key risk factors. Approximately 41% of 

those enrolled had at least one comorbidity. The most common comorbidities across the global 

population with at least 2% in either group include obesity, hypertension, Type 2 diabetes, and 

serous heart conditions. Participants who were the most vulnerable for developing COVID-19-

related symptoms were well-represented in the study overall. Looking specifically at the US 

subgroups, the percentages are similar to the overall trial population and are distributed 

between the vaccine and placebo groups.

Study COV3001 met both of it co-primary endpoints, accruing 464 primary endpoint cases 

between September 2020 and January 2021. The co-primary endpoint analysis includes all 

PCR-positive cases that were confirmed at a central laboratory. The vaccine efficacy against 

Moderate and Severe/Critical COVID-19 is approximately 67% (59.0, 73.4) after Day 14 and 

66% (55.0, 74.8) after Day 28. The lower limit of the 95% confidence interval was well above the 

 

 PC or molecular test confirmation of SA S CoV 2 infection

 

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Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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FDA requirement of 30%. Over 99% of accrued cases met Moderate to Severe/Critical case 

definitions. Therefore, the primary endpoint is representative of nearly all symptomatic COVID19 cases. Looking at the co-primary endpoints in the US, vaccine efficacy against moderate to 

severe COVID-19 is 74% (65.0, 81.6) after Day 14 and 72% (58.2, 81.7) after Day 28. The 

cumulative incidence curves between Moderate to Severe/Critical COVID-19 begin to separate 

between the Ad26.COV.S vaccine and placebo groups around 14 days after vaccination. This is 

suggestive of the timing of onset of protection.

Because of the rapid accumulation of cases due to high COVID-19 incidence during the conduct 

of the study and the time it took for central laboratory confirmation of global PCR tests, not all 

cases could be confirmed by the central laboratory at the time of the primary analysis. 

Therefore, there are two datasets. The first one consists of PCR positive COVID-19 cases 

confirmed by the central laboratory and is used in the co-primary and secondary efficacy 

analyses. However, Janssen anticipated that subgroup analyses would require a larger dataset 

to draw conclusions and wanted to look at all confirmed COVID-19 cases that required 

hospitalizations or led to deaths. Thus, they prespecified that a second dataset could be used 

that included all COVID-19 cases with a positive PCR of any FDA-approved test regardless of 

central confirmation. To justify the use of the second dataset, agreement of the positive PCR 

results were assessed from the central laboratory versus all other sources. These datasets were 

found to have high concordance. Consistency between these datasets with regard to vaccine 

efficacy also was assessed, which showed that there was less than a 1% difference between 

them for the co-primary endpoint criteria. This is true for both timepoints and therefore justified 

the use of the larger dataset.

There were several secondary endpoints in the study. In the interest of time, Dr. Douoguih

focused only on the following key secondary endpoints during this presentation:

❑ Vaccine efficacy against severe/critical COVID-19

❑ Vaccine impact on hospitalization and prevention of death

❑ Vaccine impact on asymptomatic/undetected COVID-19

Overall, vaccine efficacy against confirmed Severe/Critical COVID-19 occurring after Day 14 

was high at approximately 77% (54.6, 89.1) and increased to about 85% (54.2, 96.9) after Day 

28. There were 14 versus 60 cases of Severe/Critical COVID-19 occurring after Day 14 in the 

Ad26.COV2.S vaccine group versus the placebo group, respectively. There were 5 versus 34 

cases occurring after Day 28 in the Ad26.COV2.S vaccine group versus the placebo group, 

respectively. Looking at the Kaplan–Meier curves for confirmed Severe/Critical COVID-19 

cases, vaccine efficacy starts at Day 7 or earlier indicating early onset of protection. Protection 

continues to increase over time, which points to the potential for longevity. After Day 48, there 

were no more cases in the vaccine group versus 13 in the placebo group. Looking through Day 

56, an estimated increase in vaccine efficacy is seen to approximately 92% with no indication of 

waning thereafter. The point-wise confidence interval reflects the uncertainty around this 

estimate, which increases beyond the median follow-up at 58 days due to the small number of 

participants at those timepoints.

The data also demonstrate substantial effect of the prevention of COVID-19-related 

hospitalizations, with 93% vaccine efficacy for all PCR-positive cases from any source after Day 

14 post-vaccination. The protective effect is even more pronounced after Day 28 with 100% 

vaccine efficacy. There were 19 deaths in the study overall, 3 in the Ad26.COV2.S vaccine 

group and 16 in the placebo group. Of the deaths in the placebo group, 5 were confirmed to be 

COVID-19-associated and were reported prior to the January 22, 2021 cutoff. None of the 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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deaths in the vaccine group were COVID-19-related. A 6th COVID-19 death occurred in a 

participant in the placebo group who had a positive SARS-CoV-2 PCR test at baseline. Based 

on the study protocol, this participant was not included in the COVID-19-related death count or 

efficacy analyses. The deaths after the primary analysis were assessed, with 6 more deaths 

identified between the initial cutoff date and February 5, 2021. Of these, 2 were in the vaccine 

group and 4 were in the placebo group. One of the deaths in the placebo group was confirmed 

to be COVID-19-associated as compared to none in the vaccine group. All COVID-19-

associated deaths occurred in South Africa.

The effect of Ad26.COV2.S vaccine also was evaluated against asymptomatic, undetected 

SARS-CoV-2 infection to gain insight into the potential benefits of vaccination on transmission. 

Based on SARS-CoV-2 and IgG testing alone, 18 participants seroconverted in the 

Ad26.COV2.S vaccine group compared to 50 in the placebo group, resulting in vaccine efficacy 

of 66% (39.9, 81.1). A sensitivity analysis was performed to remove all participants with a 

positive serology result at Day 71 who had symptoms between Day 29 and Day 71. 

Seroconversion occurred in 10 of the Ad26.COV2.S vaccine group and 37 occurred in the 

placebo group. These findings are preliminary and while a formal analysis will occur once all 

participants reach 6 months post-vaccination, these data do suggest a protective effect of the 

vaccine on asymptomatic SARS-CoV-2 infection.

Dr. Douoguih next shared additional analyses among pre-specified subgroups and by countries 

with emerging variants. Vaccine efficacy against moderate to severe/critical COVID-19 is 

consistently observed across all pre-specified subgroups by age (18 to 59 years and ≥ 60 

years), comorbidity, sex, and the largest racial and ethnic groups. A lower vaccine efficacy point 

estimate with wide confidence intervals was observed for the sub-group of participants ≥ 60 

years of age with comorbidities compared with the overall population. However, the assessment 

is aligned with that of the FDA that there is an observed trend of increasing efficacy with 

narrower confidence intervals as numbers of cases in the analysis increased. Therefore, 

Janssen also aligned with the FDA that those ≥ 60 years of age are similar to any other 

subgroup and would benefit from vaccination with Ad26.COV2.S. Across 3 key countries, 

vaccine efficacy against moderate to severe/critical COVID-19 was consistently high. The 

majority of participants were enrolled in the US, Brazil, and South Africa. These also were the 

countries that contributed the most COVID-19 cases in the study. Ad26.COV2.S vaccine 

consistently protected against moderate to severe/critical COVID-19. Vaccine efficacy after Day 

28 ranged from 64% (41.2, 78.7) to 72% (58.2, 81.7) across the 3 countries.

Vaccine efficacy against severe COVID-19 was consistently high across these countries as well. 

For example, South Africa had 82% (46.2, 95.4) protection after Day 28. It is important to note 

that 95% of the sequenced samples in South Africa were associated with the new highly 

transmissible variant from the B.1.351 lineage. Upon further investigation of cases in South 

Africa, no hospitalizations occurred in the Ad26.COV2.S vaccine group and there were 6 

hospitalizations in the placebo group. There were no deaths in the Ad26.COV2.S vaccine group 

and 5 in the placebo group. These findings strongly suggest that Ad26.COV2.S vaccine is 

efficacious against this newly emerging and rapidly spreading strain.

To summarize efficacy, a single dose of Ad26.COV2.S vaccine offers substantial protection 

against COVID-19, including against hospitalizations and deaths. Across all countries, Study 

COV3001 generated high-quality and robust data at a time when the incidence of SARS-CoV-2 

was increasing, and new highly transmissible variants were emerging. Janssen’s vaccine 

demonstrated 85% efficacy against severe disease, with an early onset of protection as early as 

7 days after vaccination. Importantly for the primary analysis, there were no COVID-19 related 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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hospitalizations in the vaccine group versus 16 in the placebo group. There were no COVID-19 

related deaths in the vaccine group compared to 5 in the placebo group. Protection against 

moderate to severe disease was 66% across all countries, with an onset of efficacy evident as 

early as 14 days that increased through Day 56, especially against severe disease. In the US 

where study participants reflected the diversity of the overall US population, vaccine efficacy 

against moderate to severe COVID-19 was 72%. Protection against all symptomatic disease 

was consistent with the primary endpoint. High levels of protection were consistent across 

subgroups, countries, regions, and particular areas with high incidence of circulating variants.

Turning to the safety results, a single dose of Ad26.COV2.S vaccine is demonstrated to have an 

acceptable safety and reactogenicity profile. The results were consistent with the tolerability and 

safety of Janssen’s other adenovirus-based vaccines. Severe adverse events (SAEs), medically 

attended adverse events (MAAEs), AEs leading to discontinuation, and deaths were collected 

on the 43,783 participants who make up the FAS. In addition, a safety subset was enrolled that 

collected solicited and unsolicited AEs in 6736 participants. The primary analysis was 

conducted after the FDA guideline was met for reaching a median follow-up of at least 2 

months. The median follow-up after vaccination was 58 days. More than half of the participants 

in the full analysis had at least 2 months of follow-up. In the safety subset, nearly all of the 

participants (99.9%) completed the 28-day post-vaccination period.

The solicited AEs collected in the 7-day post-vaccination period were transient and more than 

99% were Grade 1 or 2 in severity, and all resolved within 2 to 3 days after injection. The most 

frequently reported AE was injection site pain. The frequency of Grade 3 AEs was very low 

overall, with a higher incidence in the Ad26.COV2.S vaccine group compared to placebo. For 

participants in the Ad26.COV2.S group, the most frequently reported Grade 3 event was 

injection site pain at 0.4%. There were no Grade 4 events reported. In the Ad26.COV2.S group, 

the frequency of solicited local AEs was similar between those who were seropositive for SARSCoV-2 at baseline versus those who were seronegative at baseline. The solicited systemic AEs 

were higher in the Ad26.COV2.S group versus placebo and most were transient and had a 

median duration of 1 to 2 days post-vaccination. The most frequently reported systemic 

symptoms in the Ad26.COV2.S group were fatigue, headache, and myalgia. Of the solicited 

AEs, 90% were Grade 1 or Grade 2 in severity. Grade 3 events were infrequent and were 

reported in about 2% of participants in the Ad26.COV2.S group. No Grade 4 events were 

reported for this category. Fever was reported in 9% of participants in the Ad26.COV2.S group, 

with 0.3% being Grade among those 18 to years of age and 0.1 in those ≥60 years of 

age. All fevers were reported to have started on the day of vaccination or the day after and had 

a median duration of 1 day. The reactogenicity profile overall was milder in the older age group 

compared to the younger age group.

In the safety subset at 28 days after vaccination, there were similar rates of unsolicited AEs 

between the Ad26.COV2.S and placebo groups. Rates also were balanced in the FAS for 

MAAEs, any SAE, any SAE due to non-COVID-related AEs, or any deaths. SAEs, MAAEs, and 

deaths were numerically higher in the placebo group. The imbalance between the 

Ad26.COV2.S and placebo group was driven mostly by the number of AEs associated with 

SARS-CoV2 infection. None of the deaths in the Ad26.COV2.S or placebo group were 

considered causally related to the vaccine. Janssen analyzed the occurrence of various AEs of 

interest identified by regulatory agencies and medical and scientific organizations, such as the 

Brighton Collaboration. These events include those where there is a numeric imbalance with the 

numbers higher in the Ad26.COV2.S group, including hypersensitivity and venous 

thromboembolic events. For the other events (convulsions, tinnitus, peripheral neuropathy, GBS 

and Bell’s Palsy) no causal relation with the Janssen COVID-19 vaccine could be determined. 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

18

The assessment of causality was confounded by the presence of underlying medical conditions 

frequently present in individuals with these AEs of interest. All of these events are going to be 

included in further monitoring as part of Janssen’s comprehensive pharmacovigilance plan.

Hypersensitivity events were reported in 77 (0.4%) vaccinated individuals and 65 (0.3%) 

individuals who received placebo. Some participants reported more than one sign or symptom. 

Non-serious dermatologic manifestations, particularly rash and urticaria, were the most common 

hypersensitivity AEs reported. Rash and urticaria, localized and more rarely generalized, were 

considered likely related to vaccination events reported as related by the investigator. The 

meantime to onset after vaccination was about 6 days and the mean resolution was 

approximately 13 days. The vast majority of these events were Grade 1 or 2. There were 2 

SAEs in the Ad26.COV2.S group and 1 of the placebo groups. One case of hypersensitivity was 

reported as an SAE in a vaccine recipient, with urticaria beginning 2 days following vaccination 

and angioedema of the lips, but no respiratory distress. This began 4 days after vaccination. 

The event was likely related to the vaccine. Another SAE of angioedema that occurred 23 days 

after vaccination in someone who was on enalapril was considered unrelated by the 

investigator. Both participants recovered without sequelae. The results are similar to what has 

been observed with the Ad26 vaccines.

As of February 22, 2021, there have been no cases of anaphylaxis meeting the Brighton 

Collaboration criteria in the clinical program. However, Janssen received preliminary reports

earlier in the week of 2 cases of severe allergic reaction. One of these was anaphylaxis from an 

open label collaborative study that Janssen has ongoing in South Africa in which approximately 

70,000 healthcare workers have been enrolled. Janssen will continue to closely monitor for 

these events, which is outlined more specifically in the company’s pharmacovigilance plan. Both 

arterial and venous thrombotic and thromboembolic events were similar across the 

Ad26.COV2.S placebo groups. An imbalance was seen for the venous thromboembolic events. 

Most of these participants had relevant underlying medical conditions and predisposing factors 

that may have contributed to these events, such as COVID-19 infection, prior history of deep 

vein thrombosis (DVT), new estrogen use, family history of DVT, prolonged air travel, or 

stopping anticoagulants. There is insufficient evidence to determine a causal relationship 

between these events and the Janssen COVID-19 vaccine. These events are included for 

further monitoring in the pharmacovigilance plan.

The safety data from the 43,783 participants in the Phase 3 study demonstrate that a single 

dose of Ad26.COV2.S has an acceptable safety and reactogenicity profile. Overall,

reactogenicity to Ad26.COV2.S was demonstrated to be mild and transient in nature. Grade 3 

events were rare. Most AEs were mild or moderate and generally resolved within 1 to 2 days 

post-vaccination. AEs of interest were thoroughly evaluated and Janssen will continue to 

monitor for these events in its comprehensive pharmacovigilance program. The safety profile is 

further supported by data for more than 193,000 individuals who have received at least one 

dose of Janssen’s Ad26-based vaccines in its other clinical studies and programs.

In summary, the known and potential benefits of Ad26.COV2.S outweigh the known and 

potential risks. Ad26.COV2.S offers substantial protection, especially against severe COVID-19, 

including hospitalizations and deaths irrespective of variants. Efficacy is consistent across age, 

comorbidities, race, and ethnic subgroups. For safety, Janssen has shown that a single dose of 

Ad26.COV2.S has an acceptable safety and reactogenicity profile. Results were very much 

consistent with the tolerability and safety of Janssen’s adenovirus-based vaccines in the 

platform. Plans are in place for continued safety monitoring following EUA. Now that the 

authorization has been received, Janssen will amend the COV3001 study protocol to facilitate 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

19

crossover of participants who have received placebo to receive 1 dose of the vaccine. This will 

be done as fast as operationally possible. Importantly, the vaccine is compatible within the 

existing distribution channels. It can be stored for 3 months at normal refrigerator temperatures 

and has a 2-year shelf life in regular freezers. The Janssen vaccine was specifically studied with 

a 1-dose regimen, which will greatly increase vaccination capacity and the ability to cover the 

population more quickly.

Discussion Points

Dr. Romero observed that American Indian/Alaskan Native (AI/AN) populations were not listed 

on Slide 39 although they comprise 10% of the total population, and asked what the VE and 

protection against hospitalizations and deaths were for AI/AN compared with the other groups. 

Dr. Douoguih clarified that only 1% of the 10% total population overall was coming out of the 

US. She called upon Dr. Vandebosch from Janssen to comment on the specifics for that 

particular subgroup.

Dr. Vandebosch indicated that the numbers were small in that particular subgroup. As of 14 

days, they observed 21 versus 41 cases corresponding to an efficacy of 49%. As of 28 days, 

they observed an efficacy of 32% corresponding to 18 cases in the vaccine group and 26 cases 

in the placebo group. As pointed out, the number of cases was relatively small with relatively 

widespread confidence intervals. Given that the numbers were small, they did not calculate 

severe disease or deaths in that population, but hospitalizations and deaths were not observed 

in that subgroup.

Dr. Romero asked whether the lower VE attributed to this group be related to the circulating 

variant in the countries from which these groups were recruited.

Dr. Douoguih said she did not think they had sufficient information to answer that question at 

this time. The populations coming from Latin America were spread across a number of 

countries. It is difficult to say, but they will continue to look at this as more cases are 

accumulated to determine whether in the future there will be more robust data to be able to 

address that question.

Ms. Bahta asked whether there is any information about participants who may have had a prior 

infection and their systemic or local reactions.

Dr. Douoguih indicated that they have assessed this and found that approximately 9% of the 

study population were seropositive at baseline and about 0.5% were PCR-positive. There was 

only 1 moderate case of COVID-19 in a US participant who was positive at baseline. There is 

really not enough information to be able to comment or draw any conclusions. While they did 

not have any information on systemic or local reactions for that particular participant, they did 

look at reactogenicity based on serostatus and found that local and systemic reactogenicity are 

very comparable.

Dr. Lee expressed interest in the differential timing of the separation of the curves for moderate 

to severe disease or just severe disease shown on Slide 29 where separation begins at Day 14 

and on Slide 33 that separates at Day 7. That implied to her a moderate or perhaps good 

enough immune response that is sufficient against severe or critical disease, but perhaps a 

more robust response is needed against any symptomatic disease or moderate to severe/critical 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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disease. She requested further information about the differences in the two curves and whether 

that can be related to any correlates of immunity among the participants.

Dr. Douoguih said that they have not yet identified a correlate, but they will begin to conduct that 

work that certainly will help to clarify some of these important questions. It is known that 

traditionally, it is often easier to prevent severe disease than more mild disease in terms of 

prevention of infection. It is not surprising that the separation of the curve for severe disease is 

occurring earlier. This is also reflected in the higher VE observed compared to the moderate 

and severe when combined. It maybe be that more is needed to prevent milder infections. The 

case definition was quite broad and seems to encompass the whole spectrum, including milder 

cases. That may be in part why the difference is being seen. 

Following up on Ms. Bahta’s comment about history of infection and having information 

specifically on reactogenicity, Dr. Lee agreed that it would be helpful in the future to break that 

out in order to counsel patients accordingly if there are meaningful differences. She asked 

specifically whether Janssen saw lymphadenopathy as a systemic AE.

Dr. Douoguih reiterated that there was no difference in reactogenicity. They have had 

discussions with the WG about looking at that when they do the crossover, because there might 

be more people who had COVID who would get vaccinated later on. They will try to continue to 

capture that—hopefully in large numbers. Janssen has been evaluating 26 vaccine candidates 

for quite some time and lymphadenopathy has not been a prominent feature. After several years 

and multiple studies, they looked at the solicited AE profile traditionally thought to be associated 

with Ad26 and did not include lymphadenopathy because it was not seen. They had a broader 

set of terms, but narrowed them down based on what was specific to the viral vector. That did 

not include lymphadenopathy.

Dr. Poehling asked about the experience with this vaccine and adenovirus vector in terms of 

pregnancy. She also noted that there appeared to be about 1500 people enrolled with cancer, 

HIV, or immunocompromising conditions and wondered whether any data were available on 

those participants in terms of safety and effectiveness.

Dr. Douoguih pointed out that relatively few women became pregnant after receiving the 

vaccine. There were a total of 8 in this case, making it difficult to draw any conclusions. No 

safety issues were identified post-vaccination in terms of the reactogenicity. There have been 

some spontaneous and elective abortions. Only 2 continue to be pregnant, for which the 

outcomes will be monitored. In terms of the platform, more data are coming out of the Ebola 

vaccine program in addition to the standard monitoring that Janssen does for all of its studies in 

terms of capturing pregnancies. Approximately 1600 people were vaccinated who then became 

pregnant or were pregnant at the time of enrollment. They have a few studies in which they are 

enrolling women of all trimesters in the Democratic Republic of the Congo (DRC) and in 

Rwanda on the border of the DRC where there was increased risk of Ebola. Those activities 

started in 2020. About 1500 of the women came out of those activities. Janssen is monitoring 

for the outcomes. Among about 900, no safety signals have been seen to date and the birth and 

other important outcomes seem to be in line with the background rates at the moment. From a 

reactogenicity point of view, nothing has stood out based on the numbers enrolled to date. An 

analysis has not been performed on subgroups for safety yet, though this is the plan. There are 

very few cases in the HIV-positive group to date, so conclusions cannot be drawn at this time. 

For immunocompromised patients, overall there were 2 cases. They were encouraged by the 

fact that there was quite a range of subjects who participated in the trial, but the data have not 

yet been analyzed.
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Dr. Bernstein asked what the thinking was behind choosing initially to study 1 dose rather than a 

2-dose series like other vaccines.

Dr. Douoguih indicated that choosing to study 1 dose was influenced to some extent by their 

experience with the Ebola outbreaks many years ago. For an outbreak setting, a single dose 

obviously has tremendous advantage in terms of being able to rapidly roll mass vaccination, not 

having the complexity of follow-up, and having the ability to optimize the numbers of doses 

administered. While that was one of the main reasons Janssen wanted to evaluate the single 

dose, it also was influenced by extremely strong clinical data showing full protection after a 

single dose. Once they saw that, it became clear that it was a viable option. They always 

intended to implement a 2-dose schedule as well because based on their experience, they know 

that 2 doses can be more immunogenic and could lead to more durable efficacy. With a 2-

month interval, that also means the results would be later. Both strategies can be utilized, but 

they still believe that the single dose is optimal for a pandemic setting. Should the data support 

SARS-CoV-2 vaccine becoming part of the routine immunization schedule in the future, it could 

be that a primary series for certain age groups or populations could be a 2-dose series. Janssen 

also is looking at boosting intervals out of their Phase 1/2a study.

Dr. Bernstein wondered why healthy adults ≥18 to years of age and healthy adults ≥6 years 

of age and older were chosen for the early phase studies (COV1001, COV1002, and COV2001) 

and why there was a gap. He also noted that the multi-dose vials have 3.1ml and wondered 

whether Janssen anticipates that this will result in 5 or 6 doses per vial.

Dr. Douoguih indicated that the age range is typically 18 to 45 years or 18 to 50 years, but they 

were hoping to expand to the broadest age group possible. There were concerns about starting 

to evaluate the elderly initially, so they had to generate some preliminary data in the earlier age 

group before they could go into the older age group. In early discussions with the FDA, they 

asked if they could expand the age range in case there were challenges or issues with the older 

age group. The gap was closed in Phase 3 where all of the age ranges were included. In terms 

of the 3.1ml vials, the current plan is to have 5 extractable doses per vial. It would be of interest 

to get more out of it if possible.

Dr. Sanchez observed that one criterion in the case definition was abnormal oxygen saturation 

of >93% on room air, which he found confusing. For instance, would someone with a positive 

PCR and an oxygen saturation of 95% be considered a moderate or severe case? He also 

asked what the efficacy is when the mild cases are included, whether any studies have been 

conducted in pregnant animals and women, whether the spike protein crosses into the fetal 

compartment, if coadministration with other vaccines was excluded in the studies, and whether 

the Janssen vaccine is produced with fetal cells from aborted fetuses.

Dr. Douoguih indicated that because the FDA definition for severe/critical oxygen saturation is 

93%, they wanted to make sure that those were not overlapping definition. A person with a 

positive PCR and oxygen saturation of 95% would not meet the case definition, but they may 

have other symptoms or criteria that would make them a moderate case. In terms of efficacy 

when the mild cases are included, only 4 cases in total were categorized as mild. Essentially, 

there is no difference in efficacy. Regarding pregnant women, they have conducted a 

reproductive toxicity study in which they have observed no AEs that would preclude evaluation 

in humans. There is transplacental transfer of antibody from the mom to the fetus. In terms of 

the case definition and whether the spike protein crosses into the fetal compartment, Dr. 

Douoguih called upon Drs. Sadoff and Schuitemaker to add their thoughts.
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Dr. Sadoff added that they took the moderate definition word-for-word from the FDA guidance to 

industry, which has the peculiar wording >93. That translates into 94 being the only one that 

would count for moderate, because the abnormal is <95.

Dr. Schuitemaker indicated that they have not studied whether the spike protein crosses into the 

fetal compartment in detail. It is important to understand that the spike protein in the infection 

context is membrane-bound. They have tried to reduce circulation of soluble protein, but they 

have not studied transplacental migration of even fragments of the protein at this point.

In terms of coadministration, Dr. Douoguih indicated that the Janssen studies required spacing. 

The minimum was 2 weeks for inactivated vaccine and 1 month for live replicating vaccines. 

Coadministration studies are planned with influenza vaccine and others, but these studies have 

not yet begun. The Janssen vaccine does not contain any fetal tissue.

Ms. McNally asked what the impact would be on those who have received the 1-dose primary 

series if a 2-dose primary series is determined to be safe and effective and is ultimately 

recommended.

Dr. Douoguih indicated that they first would have to determine whether there is a difference in 

efficacy with the 2-dose schedule and they are evaluating boosting intervals following a single 

dose at 6 moths. 1 year, and 2 years out. They should have some information that would help 

guide that decision-making when the time comes.

Dr. Kotton observed that on Slide 39 there appeared to be a pretty significant discrepancy 

between men and women with respect to efficacy and moderate to severe/critical COVID-19. It 

is almost 70% in men versus 60% in women. While the statistics showed some overlap, there is 

still a pretty dramatic difference. Women are generally smaller, so the vaccine dose might have 

been higher per body weight in theory. She asked whether Janssen had any thoughts about 

that.

Dr. Douoguih indicated that because of the overlapping confidence intervals, they did not view 

this as substantial. This could be evaluated in much larger numbers once the vaccine is rolled 

out.

Dr. Vandebosch added that from a statistical perspective, she agreed that the confidence 

intervals are largely overlapping. The point estimate is lower than the range of variability that 

can be expected with vaccine efficacy estimates of 66% overall. The difference that is observed 

can be due to variation and not necessarily a true difference. This aligns with the overall vaccine 

efficacy and natural variability.

It seemed to Dr. Long that there was a goodly number of subjects, pretty small numbers of 

cases, and smaller numbers of hospitalizations in the US. She asked whether that could be put 

into percentages of subjects in the placebo group who were moderately, mildly, or severely 

symptomatic. She was trying to understand the intensity of exposure, recognizing that 

participants probably were asked to mask and socially distance and that this could have 

contributed to the small number of cases. She was wondering about the intensity of exposure, 

density of exposure, the number of organisms and wondered if it was relatively small for the 

whole population if the placebo participants were not being exposed to a lot of cases in the 

pandemic and so forth to try to generalize the results.
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Dr. Vandebosch responded that from what they have seen in the trials in terms of the placebo 

group, the overall incidence was actually quite large at 20% symptomatic COVID-19 disease. A 

fraction of that was severe disease depending upon the age group. Those 18 to 40 years of age 

had a lower incidence of severe disease that was more toward mild. The group above 60 years 

of age had a higher incidence of severe disease relatively speaking. In terms of the results in 

each of the different countries and specifically in the US, the trial was conducted at the height of 

the pandemic in the US. A trial incidence of 20% is seen in the US.

Dr. Fryhofer (AMA) indicated that as a general internist, the vast majority of her patients have 

multiple comorbidities and most are older. She greatly appreciates the fact that the Janssen 

study included about 40% of patients with comorbidities and that the target for those over 60 

years of age was about 0 . She is reassured by Dr. Fink’s comments and the reaction from 

the VRBPAC panel of experts about the smaller number of older patients with comorbidities 

leading to imprecision in the efficacy results. However, they are lower and she wondered 

whether there would be any attempt to get this information out more quickly about the subset of 

older, sicker patients in order to confirm that this vaccine does work. In terms of what occurs 

after the vaccine is injected into the body, she wondered how long vaccine fragments remain, 

where they go, how the body breaks them down, and if there is any concern that remaining 

fragments could cause other issues or problems.

Regarding the comorbidity question in older adults, Dr. Douoguih said they think this is artifact. 

Because of the small number of cases and the fact that this is a subgroup of a subgroup 

analysis, they were able to have some results only because there were so many cases. After 

Day 14 in that subgroup, efficacy is completely consistent and in line with the overall dataset. At 

the 28-day endpoint after vaccination in that subgroup is where much wider confidence intervals 

are seen, because the numbers are simply lower. In terms of biologic plausibility, it does not 

make sense. The immune responses do not drop that quickly in the vaccinees. In fact, it 

plateaus and efficacy increases with time after Day 29. There is no reason to believe that it does 

not work. Of course there will be more cases, but they also looked at hospitalization in this 

subgroup and there was 82% efficacy. This is still protecting in comparable ways to the overall 

dataset, so this is believed to be a question of small numbers after Day 28 and not in line with 

the rest of the dataset that fully supports protection that is comparable in that group. In terms of 

what occurs with the vaccine after injection into the body, Janssen has conducted a number of 

biodistribution studies in animals over the years. From the point of injection once the adeno is in 

the muscle cell, it drains to the regional lymph nodes and persists an average of about 3 

months. The vector has been detected out to 6 months in a small number of animals. It is then 

subsequently cleared and no issues related to that have been observed.

Dr. Daley emphasized that everyone is concerned about the variants and efficacy of currently 

approved vaccines against these. It strikes him that they could make the most of the opportunity 

presented by the countries selected and by having sequencing data to look at the efficacy 

against variants. He is cautiously optimistic that the vaccine has high efficacy against 

hospitalization and severe disease, including against variants. He asked whether the 2-dose 

study is being conducted in sites with a high prevalence of variants so that there will be 

evidence about efficacy of the 2-dose schedule against variants.

Dr. Douoguih indicated that there is some overlap in terms of countries. They are enrolling a 

study in South Africa and the United Kingdom (UK) where B.1.117 has been circulating. 

Therefore, Janssen does expect to have some data once they begin assessing endpoints.
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Dr. Kimberlin (AAP Redbook) requested additional information about the adolescent study that 

is to begin soon in terms of the start date, ages, and plans for de-escalating to younger ages 

down to infants.

Dr. Douoguih reported that they have 2 studies that will include pediatric populations that will 

begin soon. Subsequently, they may look at immunocompromised children. The COV2001 

study had a different purposes but was amended because it was open in multiple countries and 

there was an interest expressed in adolescents. If all goes as planned, that should begin 

screening and enrollment would start during the second week of March. The age group is 12 to 

17 years of age. The aim is to acquire data as quickly as possible on the 16 to 17 year olds 

such that those data potentially could be submitted for review and incorporated as part of an 

EUA. They will then go to the 12 to 15 year olds. Janssen estimates that approximately 660 

participants will be recruited into that study. Another study comprises the whole age range of 

pediatrics, so there will be an age de-escalation beginning with adolescents and moving down 

into younger age groups. They will assess different dose levels depending on the results coming 

out of that study. The total data package intended for the pediatric population is anticipated to 

have roughly 3000 participants. The plan is for the de-escalation study to begin at the end of 

March or early April. They have been assessing feasibility and are almost ready to begin.

Dr. Shaw (ASTHO) noted that the FDA EUA recommends that providers follow the US CDC’s 

guidelines on post-vaccination observation, but in the clinical trials there were no anaphylactic 

events and there are only 2 events pending further investigation. Among the numerous benefits 

of this vaccine from an operational perspective would be the potential to forgo the observation 

period, given that the well-known adenovirus vector does not necessarily generate that type of 

anaphylaxis. He asked whether any hints of anaphylaxis have been noted other than the 2 

events in South Africa and if further details could be provided about those 2 events that might 

help state officials as they navigate the advisability of the observation period. This is important 

because this vaccine opens up the potential for true drive-through vaccination at the state and 

local levels.

Dr. Douoguih indicated that for a while, they monitored for a 60-minute period and did not see 

immediate reactions. In this program, the other studies, and for the safety run-in phase, people 

were monitored for 30 minutes. Based on seeing no immediate reactions, that was reduced to 

15 minutes. In terms of the 2 cases under investigation, the 1 case that met the Brighton 

Collaboration criteria occurred in a 39-year old woman who developed fever, swollen tongue, 

and difficulty breathing a few hours after vaccination. She had hives on her limbs and upper 

trunk, so she was admitted to the hospital. She was treated with hydrocortisone and Phenergan. 

Dr. Douoguih heard that the woman is stable, but did not know if she had been discharged. The 

other individual did not meet the Brighton Collaboration criteria. This participant was 41 years of 

age. She developed fever, chills, and other systemic symptoms that were accompanied by a 

drop in blood pressure approximately 10 minutes after vaccination. This was deemed medically 

important.

Dr. Duchin (NACCHO) requested that the CDC subject matter experts (SMEs) weigh in on the 

recommended observation period in general and for this vaccine. In terms of Slide 34 regarding 

efficacy against severe/critical COVID-19 over time, he wondered why this analysis was 

performed with only the centrally confirmed COVID cases and whether Janssen has a similar 

analysis for hospitalization.

Dr. Douoguih indicated that in the interest of time, they did not show all of the analyses. In terms 

of hospitalizations, she called upon Dr. Vandebosch to comment on what has been explored.
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Dr. Vandebosch indicated that in terms of hospitalizations, there were too few cases to assess 

and the imprecision gets larger. For the severe disease endpoints, the centrally confirmed cases 

were used to present the data. However, they also have explored the same analysis using noncentrally confirmed cases.

Dr. Fryhofer (AMA) noted in the summary provided by the FDA that one of the vaccine 

ingredients is polysorbate. For the mRNA vaccines, the CDC has listed handling patients with 

an allergy to polysorbate differently. She asked whether Janssen has thought about polysorbate 

as possibly being a reason for some of the skin issues and other allergic reactions that have 

been seen with this vaccine, and whether any of the cases with an allergic reaction were allergic 

to polyethylene glycol. The materials on the CDC website indicate that there could be a crossreaction with polyethylene glycol and polysorbate.

Dr. Douoguih said it is difficult to say because they have not really seen a pattern per se. 

Polysorbate 80 is commonly used in vaccines and foods. At this time, Janssen is not 

associating a link with that ingredient. It is not clear that participants would know if they have 

allergies to polyethylene glycol and/or polysorbate. This is an important question that Janssen 

will continue to monitor.

GRADE: Janssen COVID-19 Vaccine

Julia Gargano, PhD, MS

Epidemiologist

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention

Dr. Gargano presented the GRADE assessment for the Janssen COVID-19 vaccine. The policy 

question under consideration is, “Should vaccination with Janssen COVID-19 vaccine be 

recommended for persons 18 years of age and older during an emergency use authorization?” 

In terms of the PICO (Population, Intervention, Comparison, Outcomes) question, the population 

under consideration is persons aged ≥18 years. The intervention is a single-dose of the Janssen 

COVID-19 vaccine Ad26.COV2.S at 5×1010 viral particles administered as a single-dose 

intramuscularly (IM). The comparison is no COVID-19 vaccine. The WG identified the following 

seven outcomes as the most important for the policy question:

❑ Symptomatic laboratory-confirmed COVID-19 

❑ Hospitalization due to COVID-19

❑ All-cause death 

❑ SARS-CoV-2 seroconversion to a non-spike protein

❑ Asymptomatic SARS-CoV-2 infection

❑ Serious Adverse Events (SAEs)

❑ Reactogenicity

The potential benefits included prevention of symptomatic COVID-19 and hospitalization due to 

COVID-19, which were both considered critical outcomes. All-cause death, SARS-CoV-2 

seroconversion, and asymptomatic infection were identified as important. The potential harm of 

SAE was identified as a critical outcome, while reactogenicity of Grade 3 or 4 was identified as 

an important outcome. Hospitalization due to COVID-19 and deaths are less common and take 

additional time to occur and be documented after disease onset. The Phase 3 trials may not be 

designed or powered to evaluate the differences between treatment groups, especially at the 2-
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month time point. For the outcome of seroconversion, preliminary data using antibodies to nonspike protein among asymptomatic persons are available and have been included in the 

evidence profile. No serial PCRs were available to assess asymptomatic infection, so this 

measure was not included in GRADE evidence profile.

A systematic review was conducted to identify evidence related to the policy question and 

additional unpublished data were sought from the trial sponsor. Published articles were 

identified using various databases (Medline, Embase, and Cochrane Library, written in English, 

restricted to 2020) and search terms (coronavirus, COVID-19, SARS-CoV-2, respiratory 

(symptom, disease, illness, condition), vaccine, immunization, trial, double blind, single blind, 

placebo, comparative study, phase 3, immunogenicity, efficacy, effective, adverse, evidence, 

and variations on these terms) to identify data on vaccination with the specific vaccine 

formulation under considerations that: 1) involved human subjects; 2) reported primary data; 3) 

included adults ages 18 and older at risk for SARS-CoV-2 infection; 4) included data relevant to 

the efficacy and safety outcomes being measured; and 5) included data on the dosage under 

consideration (5×1010 viral particles, single-dose IM). Additional resources were sought, 

including unpublished data from vaccine manufacturers. Nearly 4000 records were identified 

through database searching. There was 1 published article, 2 records were obtained directly 

from the sponsor, and 3 studies were included in the evidence synthesis. Additional information 

on the identified studies was included from FDA materials prepared for the VRBPAC.

GRADE evidence types, which assess the certainty of estimates from the available data, are 

shown here:

Initial evidence type is determined by the study design. A body of evidence from a randomized 

controlled trial (RCT) starts with an initial evidence Type 1 indicating high certainty. A body of 

evidence from observational studies starts with an evidence Type 3 indicating low certainty. The 

evidence type can be downgraded due to risk of bias, inconsistency, indirectness, or

imprecision. It is possible for other considerations (e.g., publication bias or indications of dose-

 

 

 

 

 

 

 

 

 

 

 

 

 

 
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response gradient, large or very large magnitude of effect, and opposing residual confounding)

to downgrade or upgrade the evidence type.

1

To review the evidence for benefits, 1 study provided data for the critical outcome of 

symptomatic COVID-19. This was the Janssen Phase 3 RCT. The data were obtained directly 

from the sponsor. The trial included persons 18 years of age and older in the United States,

Argentina, Brazil, Chile, Colombia, Peru, and South Africa. The final scheduled analysis was 

based on data approved through January 22, 2021. The data from events recorded later have 

been incorporated into this analysis. A total of 44,325 adults were randomized to 1:1 to receive 

either vaccine or saline placebo. The numbers of persons available for analysis in the full 

analysis set (21,895 vaccine; 21,888 placebo) were used to assess SAEs, the per-protocol set 

(19,630 vaccine; 19,691 placebo) was used for most efficacy analyses, and the solicited safety 

subset (3,356 vaccine; 3,380 placebo) was used to assess reactogenicity.

In the Phase 3 trial, specimens from suspect COVID-19 cases had respiratory tract samples 

tested locally using any FDA-approved PCR assay. The protocol specified that all positive

specimens would be sent to a central study laboratory at the University of Washington for 

molecular conformation. This confirmation was specified to be used for primary endpoints. At 

the time of the interim analysis, not all local PCR tests had been tested at the central laboratory 

and of those tested, most were confirmed. The sponsor reported analyses using any PCR 

positive and centrally confirmed PCR.

The clinical trial enrollment was staggered by age group and presence of comorbidities. Those 

18 to 59 years of age and those 60 years of age and older were recruited and randomized 

separately. In each age group, the protocol specifies that 2000 without comorbidities would be 

enrolled first as a safety run-in. The plan was for safety data to be reviewed by the Data Safety 

and Monitoring Board (DSMB) before persons would comorbidities in each age group were 

enrolled. The staggered enrollment resulted in variations in the median follow-up time by 

subgroup as follows:

❑ ≥60 year-olds with comorbidities: 50 days

❑ ≥60 year-olds without comorbidities: 54 days

❑ 18-59 year-olds with comorbidities: 57 days

❑ 18-59 year-olds without comorbidities: 64 days

For the outcome of symptomatic laboratory-confirmed COVID-19, the trial’s primary outcome

called “moderate to severe/critical COVID-19” was used. This was defined as persons with a 

positive PCR who fulfilled the system criteria listed here:

≥1 of respiratory rate ≥ 20 breaths min, abnormal SpO2, pneumonia, DVT, shortness of 

breath/difficulty breathing 

OR

≥2 of Fever ( 80C), Heart rate ≥ 0, shaking chills, sore throat, cough, malaise, 

headache, myalgia, GI symptoms (nausea, vomiting, diarrhea, abdominal pain), 

olfactory/taste disorder, red/bruised toes

1 Guyatt GH, Oxman AD, Kunz R et al. GRADE guidelines: 8. Rating the quality of evidence--indirectness. J Clin Epidemiol. 2011. 

DOI:10.1016/j.jclinepi.2011.04.014.
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The sponsor looked at 2 different time points for their primary and co-primary outcomes of at 

least 14 days after vaccination and at least 28 days after vaccination. Despite the label, this 

case definition encompassed most systematic COVID-19 cases and mapped well to the 

intended outcome for GRADE. There are 4 different versions of analyses available using case 

ascertainment at least 14 and at least 28 days post-vaccination and using only cases that were 

confirmed as PCR-positive at the central laboratory or those PCR-positive from any source. The 

numbers of cases counted at Day 14 post-vaccination were 464 PCR-positive at the central 

laboratory and 682 PCR-positive from any source. At Day 28 post-vaccination, the numbers of 

cases counted were 259 PCR-positive at the central laboratory and 437 PCR-positive from any 

source. As noted earlier, confirmation of the central laboratory was incomplete at the time of the 

analysis. Of the samples that have been tested at the central laboratory, 90% were confirmed.

Case numbers were limited at 28 days post-vaccination, especially in subgroups with shorter 

follow-up time. To increase the data robustness and interpretability, 14 or more days postvaccination and any PCR-confirmed cases were selected as the outcomes to examine and 

evaluate for GRADE.

In terms of the efficacy estimates against symptomatic laboratory-confirmed COVID-19, using 

the per-protocol population for all persons at least 18 years of age, there were 173 cases 

among 19,514 persons in the vaccine arm and 509 cases among 19,544 persons in the placebo 

arm. This resulted in a vaccine efficacy estimate of 66.3% and a 95% confidence interval of 

59.9% to 71.8%. The efficacy estimate was 64.7% (57.6, 70.8) for 18 to 64 year olds, 76.5%

(59.1, 87.3) for 65 and older, and 89.7% (26.0, 99.8) for 75 and older. The efficacy estimate for 

persons with one or more comorbidities was 64.2% (52.7, 73.1). The trial is conducted in 

several countries. Efficacy varied geographically from a low of 52% (30%, 67%) in South Africa 

to a high of 74% (65%, 82%) in the US. Sequencing data on a subset of cases from South 

Africa, Brazil, and the US suggested that the variability in efficacy of estimates may have been 

related to the variants circulating in each region.

Regarding the comparison of the 4 different analyses mentioned earlier by 2 different co-primary

timepoints and whether the case was confirmed in any laboratory or by the central laboratory

only, the variations in case definition all yielded similar efficacy estimates ranging from 66.1%

(55.0, 74.8) to 66.9% (59.0, 73.4). In a comparison of the primary outcome (no evidence of prior 

infection) with 2 secondary outcomes (persons with a prior infection and mild cases), the overall 

efficacy was 66.1% (59.7%, 71.6%) when persons with evidence of prior infection were included 

and 65.2% (58.7%, 70.8%) when a broader list of symptoms was used to include mild COVID19. Note that this broader case definition including milder cases only added 15 cases overall,

again indicating that the moderate to severe COVID-19 case definition captured most 

symptomatic cases.

In terms of the GRADE evidence table for the outcome of symptomatic COVID-19, the evidence 

started at Type 1 because the data were from an RCT. Regarding risk of bias, there was some 

concern related to blinding. Participants and study staff were blinded to assignment, but some 

could have received a vaccine or placebo based on reactogenicity symptoms. This was deemed 

unlikely to overestimate the advocacy result. Therefore, the risk of bias was considered not 

serious for this and subsequent outcomes. Some concern for indirectness to the outcome was 

noted due to the short duration of observation in the available body of evidence. The vaccine 

efficacy observed at a median 2-month follow-up may differ from the efficacy observed with 

ongoing follow-up. It is possible that with longer follow-up in the timeframe of an EUA, the 

efficacy estimate for symptomatic COVID-19 could fall below the FDA-defined efficacy threshold 

of 50%. Some concern also was acknowledged for indirectness to population because of 

exclusions from the clinical trial. This was judged to be not serious. There were no other serious 
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concerns affecting the certainty assessments. The WG assessed the level of certainty as

Moderate or Type 2 for this critical outcome.

The second outcome for consideration was hospitalization due to COVID-19. The protocol 

included a definition of COVID-19 that resulted in medical intervention of at least hospitalization, 

which maps well to the PICO outcome. The protocol also used a definition of severe COVID-19

that included a COVID-19 case with ≥1 of following clinical signs at rest indicative of severe 

systemic illness; respiratory failure; evidence of shock; significant acute renal, hepatic, or 

neurologic dysfunction; admission to an intensive care unit (ICU); and/or death. This did not 

require hospitalization. Regarding the efficacy against COVID-19 needing medical intervention 

assessed at least 14 days post-vaccination, there were 2 hospitalized cases in the vaccine arm 

and 29 hospitalized cases in the placebo arm for a VE estimate of 93% (71%, 98%). Counting 

only cases occurring at least 28 days post-vaccination, there were zero hospitalized cases 

among vaccinated and 16 hospitalized cases in placebo recipients. The protocol definition of 

severe COVID-19 is at least 14 and at least 28 days for which vaccine efficacy was 76% (58%, 

88%) and 84% (54%, 97%), respectively. The analysis used in GRADE was the outcome of 

COVID-19 needing medical intervention with no evidence of prior infection at ≥14 days postvaccination. It is important to point out that the efficacy for both of the more severe outcomes 

appears higher at least 28 days post-vaccination than after 14 days, and that no COVID-19 

cases with onset at least 28 days after vaccination resulted in hospitalization.

In terms of the GRADE evidence table for hospitalization due to COVID-19, the initial evidence 

of Type 1 was downgraded 1 point due to serious concern over indirectness of outcomes

because of the short duration of follow-up. The final certainty estimate for the outcome of 

hospitalization for COVID-19 is Type 2.

The next outcome of interest was all-cause death, with data obtained from the sponsor. A total 

of 5 deaths occurred from any cause in the vaccine arm and 20 deaths from any cause occurred 

in the placebo arm for a relative risk of 0.25 and a 95% confidence interval of 0.09 to 0.67, 

indicating a statistically significant protective effect. There were no deaths attributed to COVID19 among vaccinated persons and a total of 7 among placebo recipients, including 1 in a 

participant who has PCR-positive for SARS-CoV-2 at baseline. Regarding the GRADE evidence 

table for all-cause death, there was no serious risk of bias identified and no serious concern of 

inconsistency. There was serious concern for indirectness due to the short duration of follow-up. 

There was no serious concern for imprecision. The relative risk of 0.25 (0.09 to 0.67) favored 

vaccination and the certainty estimate was Type 2.

For the outcome of interest of seroconversion to non-spike protein, preliminary data were 

available from the Phase 3 trial to evaluate this outcomes. As part of the routine trial 

procedures, blood was drawn on Days 1, 29, and 71 and then planned at Months 6, 12, 18, and 

24. Asymptomatic seroconversion was defined as detecting N-binding antibody, an antibody to 

a non-spike protein, which can distinguish between natural infection and vaccine-induced 

immunity. For the seroconversion assessment, participants who had COVID-19 symptoms or 

who were PCR-positive prior to specimen collection were excluded. It was possible to look at 

preliminary data on seroconversion between 2 time points between Days 1 and 29 and between 

Days 29 and 71. The latter has far less data available, but the WG considered it a more relevant 

measure of vaccine efficacy.
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In terms of the estimates for asymptomatic seroconversion between Days 1 and 29 when 

results were available for about 14,000 persons per group, there were 84 asymptomatic 

seroconversions among vaccinated persons and 108 asymptomatic seroconversions among 

placebo recipients for an efficacy estimate of 22.6% (-3.9%, 42.5%). The confidence interval did 

not exclude the null effect. Asymptomatic seroconversion based on the Day 71 serum collection

was used as the outcome for GRADE based on about 7% of the population, or about 1300 

persons in each arm who had data available at the time of this analysis. In the vaccine arm, 10 

persons seroconverted between Days 29 and 71. In the placebo arm, 37 persons seroconverted 

during that time. The vaccine efficacy against seroconversion was estimated to be 74.2% 

(47.1%, 88.6%). This is the outcome used for GRADE.

For the GRADE evidence table for seroconversion based on the Day 71 blood draw, no serious 

risk of bias was identified and there was no serious concern for inconsistency. Certainty was 

downgraded 2 points for a very serious concern of indirectness. Efficacy against seroconversion 

based on Day 71 serology may not be a direct measure of efficacy over a relevant period of 

time for the EUA. Additionally, serology data were only available for a subset of about 7% of the

per-protocol population. This likely does not represent all ages, comorbidities, geographies, and 

exposures to circulating variants and raises additional concern for indirectness. However, the 

relative risk of 0.26 favored vaccination and did not include harms and there was no serious 

concern for imprecision. The certainty estimate was Type 3.

In addition to the RCT already described, 2 additional studies provided data on the GRADE for 

harms. These included an unpublished Phase II RCT and a published Phase I/II RCT. The

Phase II trial included 506 person who received at least 1 dose of the Janssen vaccine among

whom 276 received the relevant dose and 78 person who received a placebo. Another Phase 

I/II trial included 323 persons who received 1 dose of the Janssen vaccine at the relevant dose 

and 163 who received placebo. In terms of the raw data on the critical outcome of SAEs 

excluding COVID-19-related SAEs and the Phase III trial for which data were collected on over 

40,000 participants, there were 83 non-COVID-related SAEs in the vaccine arm and 96 nonCOVID-related SAEs in the placebo arm. The FDA judged 3 events to be related or likely 

related to vaccination. From the Phase II trial, there was 1 SAE in the vaccine arm. In the Phase 

I/II trail, there was 1 SAE in the vaccine arm and 2 in the placebo arm. The non-fatal vaccinerelated SAEs occurring in the Phase III trial that the FDA concluded were likely related to the 

study vaccines, the SAEs included hypersensitivity, injection site pain, and systemic 

reactogenicity. For the GRADE evidence table for SAEs, there was a balance of SAEs reported 

among vaccinated and placebo groups, with 0.4% in each arm and a pooled relative risk of 0.85

(0.63 to 1.13). The certainty assessment was reduced 1 point due to serious concern of 

indirectness of outcome due to the timing. The final certainty was Type 2.

Reactogenicity was evaluated using the same 3 studies. The Janssen RCTs used the solicited 

events for 7 days following vaccination and the GRADEing scales shown here:

❑ Local reactions (pain at injection site, redness, swelling):

– Grade 3: pain at injection site that prevents daily activity or use of narcotic pain 

reliever; redness > 10 cm; and swelling > 10 cm.

– Grade 4: hospitalization for severe pain at the injection site, necrosis (redness and 

swelling categories) or exfoliative dermatitis (redness category only).

❑ Systemic events (fever, nausea, headache, fatigue, muscle pain):

– Grade 3: fever >38.9°C to 40.0°C, nausea, fatigue, headache, or muscle pain that 

prevents daily activity or use of narcotic pain reliever.
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– Grade 4: fever >40.0°C, nausea, fatigue, headache, or muscle pain that require 

hospitalization or prevents basic self-care.

Regarding the numbers and proportions of Grade 3 events in the vaccine and placebo arms for 

the 3 trials, the proportion reporting any Grade 3 event range from 2.2% to 5% percent in the 

vaccinated group and from 0 to 0.7% in the placebo group. Pooling the data from the 3 trials, 

the relative risk estimated for any Grade 3 or 4 event was 3.42 with a 95% confidence interval 

from 2.20 to 5.31. There was no serious concern for risk of bias, inconsistency, indirectness, or 

imprecision. The final certainty was Type 1.

To summarize the GRADE assessment for the Janssen COVID-19 vaccine, in terms of benefits,

the available data indicate that the vaccine is effective for preventing symptomatic COVID-19 

with a evidence of Type 2. For hospitalization and death, the available evidence strongly favors

the intervention and the evidence is also Type 2, The preliminary data from Day 71 indicated 

efficacy against asymptomatic seroconversion with Type 3 evidence. There were no data 

available to assess asymptomatic infection using routinely collected nasal swab specimens for 

PCR testing. In terms of harms, the available data indicate that SAEs were balanced between 

the vaccine and placebo alarms with evidence of Type 2. There were 3 participants with SAEs

use that the FDA judged to be related to the vaccine among over 21,000 vaccinated. Grade 3 

reactogenicity was 3 times more common among vaccine recipients than among placebo 

groups. There were no Grade 4 reactions and Grade 3 reactions were uncommon. The 

evidence type for reactogenicity was Type 1.

In conclusion, the Phase 3 RCT of the Janssen COVID-19 vaccine was conducted on 3 

continents during a time of high COVID-19 incidence while viral variants were emerging. The 

trial exceeded the target numbers of cases to meet its primary endpoint by the time the required 

median 2-month follow-up was complete. The vaccine efficacy estimates for the Janssen 

COVID-19 vaccine were 66% for symptomatic laboratory-confirmed COVID-19, 93% for 

hospitalization due to COVID-19, 75% for all-cause death, and 74% for asymptomatic 

seroconversion. No deaths due to COVID-19 were identified among vaccine recipients and 7 

deaths due to COVID-19 were identified among placebo recipients. No serious safety concerns 

were identified in the RCTs, with balanced reports of SAEs between arms of 0.4% each. Grade 

3 local or systemic reactions were more common among vaccine than placebo recipients and 

were reported by less than 3% of vaccinated subjects. The certainty and the estimates for all 

critical benefits and harms was Type 2 or moderate, with certainly impacted by concern for 

indirectness because of the short duration of follow-up in the available body of evidence. 

Discussion Points

Dr. Lee observed that 14 days after 2 doses is different from 14 days after 1 dose. Therefore, it 

makes sense to assess the 28-day outcome after Dose 1 for the Janssen vaccine as it seems 

somewhat more equivalent in terms of understanding the impact. She found it extremely 

promising that a single dose of the Janssen vaccine can prevent hospitalizations and deaths 

and that it appears to offer protection against variants. Interestingly, the asymptomatic 

seroconversion efficacy of 74% between days 29 and 71 is almost equivalent to what was seen 

for symptomatic disease at 28 days. The potential to interrupt transmission, for which there is 

growing evidence, is the most promising information she has heard. The efficacy for all-cause 

death is substantial. She has been so focused on deaths directly due to COVID-19 that she had 

not thought as much about the other complications of COVID-19 infection that lead to all-cause 

death. The protective effect is remarkable, so she wondered if Dr. Gargano and/or others could 

comment on understanding what those deaths were as the benefit of COVID-19 vaccination 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

32

may be broader than preventing COVID-19 deaths. While it is not appropriate right now during 

the EUA, perhaps a future G ADE should e amine “long-haul” COVID-19 as well as the 

outcomes and what the vaccine’s impact might be for the longer-term effects of COVID 

infection.

Dr. Gargano indicated that she did not have a slide that showed the causes of death for all of 

the all-cause deaths, but some were due to respiratory causes such as pneumonia determined 

not to be COVID and she can provide more details at a later time. She agreed that long-haul 

COVID would be very interesting to examine further, though not available at this time due to the 

2-month follow-up.

Dr. Chen requested a reminder of whether there was a difference in the immunocompromised 

population studied with this vaccine. It seemed to him that there was a more restrictive definition 

for the so-called abnormal function of the immune system in this study. Perhaps there is a lack 

of efficacy information, and maybe even the safety information generated with these studies. 

This is a very important subpopulation of the target population in terms of vaccinating.

Dr. Gargano said that the wording of the inclusion criteria of who could be included in the 

immunocompromised population was somewhat different. The numbers available at this time 

are just too small to draw any conclusions about efficacy in that population.

Dr. Romero emphasized that the data for AI/AN are very weak as shown in the original 

presentation.

EtR Framework: Janssen COVID-19 vaccine

Sara Oliver, MD

LCDR, U.S. Public Health Service

Co-lead, Advisory Committee for Immunization Practices COVID-19 Vaccines WG

COVID-19 Response

Centers for Disease Control and Prevention

Dr. Oliver presented the EtR Framework for the Janssen COVID-19 vaccine. As a reminder, the 

EtR Framework is a structure to describe information considered in moving from evidence to 

ACIP vaccine recommendations. It also provides transparency around the impact of additional 

factors on deliberations when considering a recommendation. The policy question being 

addressed in this Et was, “Should vaccination with the Janssen COVID-19 vaccine be 

recommended for persons 18 years of age and older under an Emergency Use Authorization.” 

In terms of the PICO question, the population is persons 18 years of age and older, the 

intervention is the Janssen COVID-19 vaccine, and the comparison is no vaccines. The 

outcomes are the same as detailed in the GRADE presentation. These are the domains for the 

EtR Framework discussed during this session:
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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As done before, updates will be made to make the questions applicable to the Janssen vaccine 

and to COVID-19 exercise.

The primary question for the Public Health Problem domain is, “Is COVID-19 disease of public 

health importance?” As of February 25th, there have been over 28 million cases. However, 

cases have been declining since late January and the 7-day moving average is now just over 

67,000 cases per day. This is down from a peak of almost 250,000 cases per day in January.

As of February 25th, there have been over 500,000 COVID-19 deaths reported to CDC, with a 7-

day moving average at 2100 deaths per day. This is down from the peak of over 3300 deaths 

per day in late January. To summarize the available evidence2, the cumulative hospitalization 

rate between March 2020 and February 20, 2021 was 452 per 100,000 population. Among 

those hospitalized, 25% required intensive care and 11% died. The cumulative mortality 

between January 2020 and February 25, 2021 with 153 per 100,000 population. As was 

highlighted in a report published recently, the life expectancy dropped nearly a full year for the 

US population using data from the first half of 2020. In addition, disparities were noted by race

in that the life expectancy for the Black population declined by 2.7 years and 1.9 years for the 

Hispanic population. The emerging landscape of the SARS-CoV-2 variants definitely impacts

the public health problem. This emerging landscape requires urgency with vaccinations to build 

population immunity. The WG’s judgment was that yes COVID-19 is of public health importance.

In addition to the overall GRADE presentation, the questions to determine benefits and harms

are, “How substantial are the desirable anticipated effects, the undesirable anticipated effects, 

and do the desirable effects outweigh the undesirable effects?” A detailed review of the benefits 

and harms through GRADE was just presented, but Dr. Oliver walked through the highlights and 

some additional information. As a reminder, the outcomes GRADEed were 14 days postvaccination. The clinical trial demonstrated efficacy against symptomatic laboratory-confirmed 

COVID-19 with an efficacy of 66.3%. This was determined to have moderate certainty relative to 

the policy question under the EUA. For hospitalization, 31 events occurred of which 29 were in 

the placebo group and 2 of which were in the vaccine group. Vaccine efficacy against 

hospitalizations with 93%. There also was moderate certainty in this estimate. For all-cause 

2 https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html; https://gis.cdc.gov/grasp/COVIDNet/COVID19_5.html; 

https://www.cdc.gov/nchs/data/vsrr/VSRR10-508.pdf

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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mortality, 5 deaths occurred in the vaccine group and 20 occurred in the placebo group for an 

estimate against all-cause mortality of 75%, again with moderate certainty in this evidence.

Preliminary data were available to assess vaccine efficacy against seroconversion between 

Days 29 and 71 based on the first 7% of specimens tested. The analysis was based on 

detection of the N-binding antibody among persons who remained asymptomatic and did not 

have a positive SARS-COV-2 PCR at any time in the study. Between 4 and 10 weeks after 

vaccination, 10 (0.7%) of vaccine recipients seroconverted compared to 37 (2.8%) of placebo 

recipients for a vaccine efficacy against asymptomatic seroconversion of 74%. While this data is 

encouraging, given the single time point only 10 weeks after vaccine receipt and that this is less 

than 10% of the study population, there was low certainty of this evidence. Similar efficacy was 

noted across age, sex, race, and ethnicity categories and those with underlying medical 

conditions 14 or more days post-vaccination. These estimates all coalesce around the overall 

efficacy endpoint of 66%. There was higher efficacy against severe outcomes than for any 

symptomatic COVID, with efficacy against COVID-19-associated deaths at 100%. Efficacy 

estimates for severe outcomes assessed at 28 days or more post-vaccination were even higher, 

with 83% for severe disease and 100% for hospitalization. Efficacy against severe illness 

remained high across world regions, suggesting protection against severe illness even with 

variant strains.

For a summary of possible harms, SAEs were reported in a similar proportion among recipients 

of vaccine and placebo. There was moderate certainty in this evidence. The reactogenicity 

outcome graded was severe for Grade 3 reactions. Overall, a Grade 3 or higher reaction was 

reported by 2.5% of those receiving the vaccine and 0.7% for placebo. This is graded with a 

high certainty of evidence. Local reactions occurring within 7 days were common. Pain at the 

injection site was the most common. Systemic reactions within 7 days were common as well,

with headache, fatigue, and myalgias as the most common symptoms reported. Most symptoms 

resolved after 1 to 2 days. Including local and systemic AEs by age group, reactogenicity was 

higher among vaccine compared to placebo recipients and in younger compared to older adults. 

Overall Grade 3 reactions were rare in the range of 1% to 2% percent of participants and again 

more common in the younger age. As was done with other COVID vaccines, there will be a 

website summarizing reactogenicity data on the CDC and ACIP websites to help inform 

providers and patients about symptoms post-vaccination seen in the clinical trials.

There were several AE imbalances of note. Urticaria events that FDA determined could possibly 

be related to the vaccine, tinnitus, and thromboembolic for which FDA stated there was 

insufficient data to determine a causal relationship. In addition for thromboembolic events, many 

of the participants had predisposing conditions. However, FDA recommends surveillance for 

further evaluation of thromboembolic events.

As this is the third COVID vaccine with an EUA, the WG wanted to provide one slide with 

thoughts on how this vaccines is in the overall program. There were no trials that compared 

efficacy between vaccines in the same study at the same time. All Phase 3 trials differed by 

calendar time and geography. This is important because it means that the vaccines were tested 

against different circulating variants and in settings with different background incidence. This 

limits the ability to draw specific comparisons with each of the Phase 3 trials. All authorized 

COVID vaccines have demonstrated efficacy against symptomatic laboratory-confirmed COVID

ranging from 65% to 95%. All authorized COVID vaccines have demonstrated high efficacy 

against COVID severe enough to require hospitalization at 89% or higher. In the vaccine trials,

no participants who received a COVID-19 died from COVID. The Moderna and Janssen trials 

each had COVID deaths in the placebo arm.
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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This table shows a summary of GRADE from earlier, with each evidence type listed:

Outcome Importance Design

(# of 

studies)

Findings Evidence

type

Benefits

Symptomatic laboratoryconfirmed COVID-19 Critical RCT (1) Janssen COVID-19 vaccine is effective in preventing symptomatic 

COVID-19 2

Hospitalization due to 

COVID-19 Critical RCT (1) Janssen COVID-19 vaccine prevents COVID-19-resulting in hospitalization 2

All-cause Death Important RCT (1) Janssen COVID-19 vaccine is associated with a lower risk of both 

all-cause death and death due to COVID-19 2

SARS-CoV-2 

seroconversion Important RCT (1)

Data from day 71 serology indicates that Janssen COVID-19 vaccine 

prevents seroconversion during the available follow-up period; data 

support an effect on prevention of asymptomatic infection

3

Asymptomatic SARS-CoV-2 

infection Important No Studies No systematically collected PCR data are available to develop an estimate for this outcome ND

Harms

Serious adverse events Critical RCT (3) SAEs were balanced between vaccine and placebo arms. 3 

participants had SAEs judged by FDA as likely related to vaccination 2

Reactogenicity Important RCT (3) Severe reactions were about 3 times more common in vaccinated vs. 

placebo; any grade ≥ reaction was reported by 2.5% of vaccinated 1

Evidence type: 1=high; 2=moderate; 3=low; 4=very low; ND, no data

In summary, the WG felt that the desirable anticipated effects were large and that the 

undesirable anticipated effects were small. Based on this, the WG felt that when considering 

how the desirable effects balance with undesirable effects, it favors the intervention—the 

Janssen COVID-19 vaccine.

The questions for the values domain are, “Does the target population feel that the desirable 

effects are large relative to undesirable effects?” and “Is there important uncertainty about, or 

variability in, how much people value the main outcome?” As detailed previously, a review was 

conducted of the scientific literature, media, and reports updated through February 26, 2021. 

The overall acceptability of a COVID vaccine was moderate,

3 with the proportion intending to 

receive the vaccine ranging from 42% to 86%. A recent survey in February showed that 46% 

would receive the vaccine as soon as possible, 27% plan to wait and see, and 18% said they 

would not receive it.

4 Another recent survey detailed the populations with the highest estimates 

for people who do not intend to receive a COVID vaccine, particularly younger adults, women,

non-Hispanic Black adults, adults living in non-metropolitan areas, and those with less 

education and income and without health insurance.5 This graphic combines the data from now 

45 surveys, with the proportion reporting positive vaccine intent by month of data collection, with 

bubbles proportional to the survey sample size:

3 APNORC; Harris; Fisher Ann Intern Med.; ICF; Kreps JAMA Netw Open.; Lazarus Nature Med.; Malik EClinicalMedicine.; Pogue 

Vaccines.; Reiter Vaccine.; Thunstrom SSRN. Szilagyi JAMA. Axios-IPSOS. Pew. KFF. ABC News-IPSOS. Quinnipiac. Monmouth.

4 KFF COVID-1 Vaccine Monitor February 2021. February 26, 2021. https://www.kff.org/coronavirus-covid-19/poll-finding/kff-covid19-vaccine-monitor-february-2021/

5 Nguyen KH, Srivastav A, Razzaghi H, et al. COVID-19 Vaccination Intent, Perceptions, and Reasons for Not Vaccinating Among 

Groups Prioritized for Early Vaccination — United States, September and December 2020. MMWR Morb Mortal Wkly Rep 

2021;70:217–222. DOI: http://dx.doi.org/10.15585/mmwr.mm7006e3
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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In addition, surveys with multiple time points are shown with the same color. From March to 

September, vaccine intention slowly declined. However, since the winter when there were 

tangible data on safety and effectiveness of vaccines, it appears intent has increased slightly 

and leveled out around 60%.

This map shows the percentage of adults who have not yet received a COVID vaccine but

definitely will once available, with the darker shade of green representing higher intent to 

vaccinate using data from early February and showing that the likelihood of receiving a COVID19 varies by state and region of the country:

 

 

 

 

 

 

 

 

 

 

 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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Intent to receive a vaccine by race and ethnicity come from data from surveys around 

theoretical vaccines when the questions were asked before data was known on any specific

vaccine. Two of the surveys were conducted in January or February 2021 when information was

known around specific vaccines.6 Overall, vaccination intention varied substantially by race,

ethnicity, and socioeconomic status. Common reasons for positive intentions included protecting

self, family, and community from COVID; belief that vaccines are safe; and the ability to resume 

social activities. Common concerns included vaccine side effects and uncertainty around 

vaccine safety. Most of the data presented so far were for overall COVID vaccines. However, 

one recent survey addressed a situation that could be related to this specific vaccine. This 

survey asked about a 2-dose vaccine with high efficacy compared to a 1-dose vaccine with a 

moderate efficacy estimate. Over half would choose the 2-dose vaccine with higher efficacy, 7% 

would choose the 1-dose vaccine, and 21% would take either. there wasn't a follow-up question.

There was a follow-up question that asked of those who stated that they would choose the 2-

dose vaccine would wait a month to receive that 2-dose vaccine or would receive the 1-dose 

vaccine now. Of those who initially said that they would want the 2-dose vaccine, 28% said they 

would get the 1-dose vaccine now instead of waiting.7 Limitations for the data include that most 

surveys are conducted prior to the availability of information on the Janssen vaccine and 

convenience samples may not be representative.

The WG interpretation of the first question was that yes, the desirable effects are large relative 

to undesirable effects. However, they also felt that there was probably important uncertainty or 

variability in how much people value the main outcomes.

The question addressed for the acceptability domain was, “Is the Janssen COVID-19 vaccine 

acceptable to key stakeholders?” A review of the literature was conducted as well as other 

relevant information, including news media. There are still no published provider knowledge,

attitude, and practices surveys. Previously, the WG presented a survey of State Health Officers8

demonstrating concern with vaccine hesitancy, safety, and communications. They were recently

made aware of concern from jurisdictions regarding vaccine supply and unmet demand in a 

letter to the President from the National Governors Association (NGA) Executive Committee.

9

The logistics of this particular vaccine may make it more acceptable to a wide variety of 

stakeholders. This is a single-dose vaccine with more convenient storage and does not require

dilution. In addition, COVID vaccination programs have been implemented in a variety of 

settings, including state and local health departments, health care sites and hospitals, mass 

vaccination clinics, long-term care facilities (LTCF), and retail pharmacies. As of February 27, 

2021, over 72 million doses have been administered. Over 48 million people have initiated the

series, over 23 million have completed 2-dose series, and over 7 million doses have been given 

in LTCF.

10 Addressing the main question for this domain, the WG felt that the Janssen COVID19 vaccine was acceptable to key stakeholders.

6 Szilagyi PG, homas K, Shah MD, et al. ational rends in the US Public’s Likelihood of Getting a COVID-19 Vaccine—April 1 to 

December 8, 2020. JAMA. 2021;325(4):396–398. doi:10.1001/jama.2020.26419

7 NORC AmeriSpeak, Feb 11-15, 2021. CDC unpublished data.

8 CDC COVID-19 Response Team.

9 National Governors Association. Executive Committee Letter To President Regarding Vaccine Distribution 

Process. https://www.nga.org/advocacy-communications/executive-committee-letter-to-president-regarding-vaccine-distributionprocess/

10 COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#vaccinations.
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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The question for the feasibility domain was, “Is the Janssen COVID-19 vaccine feasible to 

implement?” he specific characteristics of this vaccine likely make it more feasible to 

implement. Vaccine shipment and storage is at refrigerator temperatures and is a single-dose 

series. To address possible financial barriers, COVID-19 vaccines are provided free of charge. 

However, as discussed previously, health systems or health department could incur cost for 

vaccine implementations and clinics. There is also concern for personal investments in time and 

travel to obtain the vaccine that may be a barrier for some groups. However, for the Janssen 

product, these costs related to implementation or vaccine receipt would presumably be less for 

a 1-dose compared to a 2-dose schedule. For complexity of recommendations, 1 adenoviral 

vector vaccine and 2 mRNA vaccines under an EUA with a different number of doses, dosing 

intervals, and storage and handling requirements may make vaccine recommendations more 

complex. In addition, there is the potential for emerging challenges related to managing choice 

or preference for providers and consumers for different products.

In terms of access to vaccines, adding a third vaccine will increase access in terms of total 

vaccine doses available. However, access to vaccines still could be limited for people who are 

underserved or live in rural or other hard-to-reach areas. Jurisdictions need to consider 

differential access when planning vaccination locations, communicating vaccination information,

and scheduling appointments.11 A variety of programs are coming on board including the 

Federal Retail Pharmacy Program12, Federally Qualified Health Center Program13, and the 

FEMA Community Vaccination Centers14 which should further expand access. Finally, a vaccine 

without freezer requirements could be used in individual provider offices once supply allows. 

Based on these considerations, the WG felt that yes, COVID-19 vaccine is feasible to

implement.

The question for the resource use domain was, “Is the Janssen COVID-19 vaccine a reasonable 

and efficient allocation of resources?” As has been discussed previously, health-related costs 

have been estimated at $8.5 trillion.15 It is worth noting that this estimate was provided before 

the December/January surge in cases, so it is likely even higher at this point. The US 

Government (USG) has committed over $10 billion to provision of vaccines

16 and is committed 

to purchasing hundreds of millions of doses of vaccines over the next several months. A recent 

study estimated the cost per quality adjusted life year (QALY) for a hypothetical vaccine. This

vaccine was not provided under the current situation, is not provided free-of-charge, and 

modeling did not consider societal costs associated with the pandemic. However, even with 

these limitations, there were many circumstances where the vaccine was cost-saving depending

on the target population.17 Finally, one modeling study concluded that there are only limited 

situations that would favor foregoing currently available vaccines for higher efficacy vaccines 

11 COVID-19 Vaccination Program Interim Playbook for Jurisdiction Operations. October 29, 

2020   https://www.cdc.gov/vaccines/covid-19/covid19-vaccination-guidance.html

12 CDC. Understanding the Federal Retail Pharmacy Program for COVID-19 Vaccination. https://www.cdc.gov/vaccines/covid19/retail-pharmacy-program/index.html 

13 CDC. Ensuring Equity in COVID-19 Vaccine Distribution. https://www.cdc.gov/vaccines/covid-19/planning/health-centerprogram.html

14 FEMA. https://www.fema.gov/press-release/20210216/fema-supports-vaccine-distribution-amid-winter-weather-response 

15 1 Cutler and Summers. 2020. JAMA. “ he COVID-1 pandemic and the $16 trillion virus.”

16 Source: https://www.hhs.gov/about/news/2020/05/15/trump-administration-announces-framework-and-leadership-for-operationwarp-speed.html

17 Kohli M, Maschio M, Becker D, Weinstein M. "The Potential Public Health and Economic Value of a Hypothetical COVID-19 

Vaccine in the United States: Use of Cost-Effectiveness Modeling to Inform Vaccination Prioritization." Vaccine 2021 Feb 12; 39(7): 

1157–1164.
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

39

available later in the pandemic. These situations were only for a vaccine with efficacy lower than 

the current FDA threshold for an EUA.

18

The precise cost-effectiveness analysis and economic impact of vaccination depends on a 

number of factors that are currently unknown, including real-world vaccine effectiveness and 

duration of protection, vaccination coverage levels and speed of vaccination, implementation 

costs associated with large vaccination program, and the overall course of the pandemic. The 

WG again concluded the cost-effectiveness may not be a primary driver for decision-making 

during the pandemic and for vaccine use under an EUA. This will need to be reassessed in the 

future as more becomes known about the variables discussed here. However, during the 

pandemic, the data show that the best utilization of resources is to employ all available vaccines 

with acceptable vaccine efficacy. This will save cost and lives. Based on the current situation,

the WG felt that yes, the Janssen COVID-19 vaccine is a reasonable and efficient allocation of 

resources.

The question for the health equity domain was, “What would be the impact of the Janssen 

COVID-19 vaccine on health equity?” A number of groups have experienced increased COVID19 disease or decreased uptake of COVID-19 vaccine, including the following:

❑ Racial and ethnic minority populations and tribal communities

❑ People living in poverty or with high social vulnerability

❑ Essential workers:

– Almost one quarter live in low-income families19

– Some racial/ethnic minority populations disproportionately represented in subsets 

of essential workers, e.g., public transit, building cleaning services, construction, 

food and agriculture 19, 20, 21 

❑ Residents in congregate settings, such as long-term care facilities, correctional/detention 

facilities, homeless shelters, and group homes

❑ People with disabilities

❑ People with substance abuse disorders

❑ Sexual and gender minorities (social or structural inequities leading to health disparities)

Based on states’ initial vaccine allocation plans, only 19 (38%) states used a Social Vulnerability 

Index (SVI) to deliver vaccines more equitably.

22

 There was a national survey in early January

2021 that showed that Black persons were 52% less likely than White persons to be vaccinated 

or plan to get vaccinated.23 As of February 26, 2021, there is a lower proportion of Black and 

Hispanic persons who have received the vaccine compared to the demographics of the overall 

population.

24

18 Bartsch SM, O'Shea KJ, Wedlock PT, et al. The Benefits of Vaccinating With the First Available COVID-19 Coronavirus Vaccine. 

American Journal of Preventive Medicine. 2021 Jan 19.

19 1Rho HJ, Brown H, Fremstad S. A basic demographic profile of workers in frontline industries. April 2020. Washington, DC: 

Center for Economic and Policy Research;2020. https://cepr.net/a-basic-demographic-profile-of-workers-in-frontline-industries 

20 2Bui DP, McCaffrey K, Friedrichs M, et al. Racial and ethnic disparities among COVID-19 Cases in workplace outbreaks by 

industry sector — Utah, March 6–June 5, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1133–8. DOI: 

http://dx.doi.org/10.15585/mmwr.mm6933e3

21 3Waltenburg MA, Rose CE, Victoroff T, et al. Coronavirus disease among workers in food processing, food manufacturing, and 

agriculture workplaces Emerg Infect Dis. 2021 Jan. https://wwwnc.cdc.gov/eid/article/27/1/20-3821_article

22 Schmidt et al. Equitable Allocation of COVID-19 Vaccines. 2020: https://scholarship.law.georgetown.edu/facpub/2333/

23 Kim et al. https://www.medrxiv.org/content/10.1101/2021.02.16.21251769v1

24 CDC. https://covid.cdc.gov/covid-data-tracker/#vaccination-demographic as of Feb 17 2021 , and US Census Bureau 10-year 

July 2019 National Population Estimates
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There are specific characteristics of the Janssen COVID-19 vaccine that could impact health 

equity. In terms of storage, handling, and administration requirements, this refrigerator-stable 

vaccine will facilitate the ability of the vaccine to get into most community settings and mobile 

sites once supply allows. A single-dose schedule could be an advantage to equity, particularly in 

settings or populations where follow-up for a second dose would be challenging. It also would

allow for increased vaccine options and more doses available. This vaccine could make it easier 

to reach some disproportionately affected groups, such as persons experiencing homelessness,

rural resident, justice-involved persons, disabled persons, homebound persons, or persons with 

limited access to health care. Community engagement and education will be important as new 

vaccines are utilized. Finally, equity and vaccine program implementations are closely linked. 

Advancing health equity requires community engagement and focused efforts to identify and 

reduce vaccine access and confidence-related25 barriers to vaccination among groups who 

experience a disproportionate COVID-19-related morbidity. In addition, wherever possible when 

setting and supply allow, consideration should be given to extending choices for COVID-19 

vaccines.

The WG felt that the impact of the Janssen COVID-19 vaccine would be to increase health 

equity. The feasibility of the Janssen COVID vaccine to be implemented in a wider variety of 

settings is an opportunity to improve equitable access to an effective COVID-19 vaccine.

This table summarizes the EtR domains, questions, and WG judgments from everything that 

was just presented:

25 CDC. COVID-19 Vaccination Program Interim Playbook for Jurisdictions Operations Annex: Considerations for Increasing COVID19 Vaccination, Reaching and Increasing Uptake in Priority Populations (January 2021 Version 

1.0). https://www.cdc.gov/vaccines/covid-19/downloads/COVID-19-vaccination-program-playbook-annex.pdf

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
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After reviewing the data, the WG provides a judgment on the balance of consequences based 

on the following categories:

❑ Undesirable consequences clearly outweigh desirable consequences in most settings

❑ Undesirable consequences probably outweigh desirable consequences in most settings

❑ The balance between desirable and undesirable consequences is closely balanced or 

uncertain

❑ Desirable consequences probably outweigh undesirable consequences in most settings

❑ Desirable consequences clearly outweigh undesirable consequences in most settings

❑ There is insufficient evidence to determine the balance of consequences

The WG felt that the desirable consequences clearly outweigh undesirable consequences in 

most settings. In addition, after reviewing the totality of information presented in the EtR 

Framework, the WG discussed the type of recommendation proposed to ACIP. The options are:

❑ We do not recommend the intervention

❑ We recommend the intervention for individuals based on shared clinical decision-making

❑ We recommend the intervention

Based on the totality of data presented, the WG has proposed to recommend the intervention 

the ACIP.

Discussion Points

Dr. Whitley-Williams (NMA) found it more reassuring to see 13% African American and 14% 

Hispanic or LatinX participation in the US and asked whether there are data on the AEs by 

race/ethnicity. She understood that the total SAEs are small in numbers to begin with. Given the 

requirement that all participants are encouraged to remain in the study up to 2 years to assess 

efficacy, safety, immunogenicity, she wondered if any information was available about how 

many of the URM participants have remained in the study and if those in the placebo group 

were offered vaccine and also are being followed in the 2-year follow-up study.

Dr. Goldman (ACP) said that if this vaccine is approved for recommendation by ACIP, it will be 

important to be very clear on the messaging regarding the lack of comparison of the vaccine, 

but that in and of itself, this appears to be a very safe and effective vaccine based on good data. 

They must ensure that the public understands that the best vaccine is the one to which they can 

get access. He encouraged Governors and jurisdictions to adhere to the ethical framework in 

order to get the vaccine out to the most people possible. As a primary care physician (PCP), he 

emphasized that many PCPs are eager to be able to vaccinate their populations. This vaccine 

may be very helpful in achieving that goal with the refrigerator-stable storage. He inquired as to 

whether Dr. Oliver could provide more details about the thromboembolic events that were 

reported.

Dr. Oliver called upon representatives from Janssen and the FDA to provide an overview of the 

thromboembolic events.

Dr. Douoguih indicated that Janssen has observed a slight imbalance in thromboembolic 

events, although there is not a big difference between groups. As mentioned during her 

presentation, a large proportion of participants who have had these events had predisposing 

factors, underlying medical conditions, that plausibly could have contributed to these events. 

Right now, they do not believe there is a causal association with the vaccine. However, they 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

42

have committed to monitor this post-authorization beginning immediately. As the vaccine is 

rolled out, it is Janssen’s intent to e amine these events closely—keeping in mind that COVID19 is also an underlying factor that will have to be included in the assessment.

Dr. Long expressed appreciation that the WG’s judgement that the level of confidence in

prevention of asymptomatic infection is tempered by low numbers. This is important to

remember, because it would be the opposite of every instance that is known in terms of efforts 

to prevent severe disease with basically IgG antibody that is derived from an IM injection. It 

prevents more invasive and more severe disease better than it does upper respiratory tract or 

asymptomatic disease. It would be great news if this vaccine prevents some asymptomatic

infection, especially transmission from that. She appreciated that the WG concluded that the 

confidence in that is not high. To discuss these vaccines one against the other or one compared 

with another and nuances of recommendations, she was especially appreciative of some of the 

public comments as she has been thinking about some of these issues, age groups, and the 

difficulty in reaching some populations. She asked whether the plan was to focus the first day of 

the meeting on the recommendation and put off other nuances until the next day.

Dr. Romero indicated that ACIP’s mandate was to make recommendations regarding this 

specific vaccine and each specific vaccine as it comes forward. At this time, they were not 

tasked with comparing the vaccines to one another and making specific recommendations for 

each one independent of the other. They could discuss this further during the second day of the 

meeting, but at this moment that was not a decision they were ready to make.

Dr. Duchin (NACCHO) expressed appreciation for the presenters for highlighting that it is 

inappropriate to try to compare the 3 available vaccines directly with respect to effectiveness. It 

is clear that they all provide a high level of protection against what is more important, which is 

severe illness, hospitalizations, and deaths. However, it seemed to him that they may be able to 

compare the reactogenicity and particularly the severe and Grade 3 systemic reactions among 

the available vaccines. It appeared to him that the Janssen vaccine has significantly fewer such 

severe reactions. He wondered whether someone would care to comment on that aspect of the 

vaccines.

Dr. Oliver said she thought they also would caution against event comparing reactogenicity 

across the trials, given that this very much depends upon how it was asked in the trials and the 

number and type of symptoms that were asked. These vaccines will be closely monitored as 

they are rolled out and there will be post-authorization safety data that the WG will present to 

ACIP as it becomes available.

Dr. Eckert (ACOG) stated that on behalf of the America College of Obstetricians and 

Gynecologists, she was very happy that Janssen has data for this vaccine being used in 

pregnancy with the Ebola platform. While acknowledging that this information is present in the 

VRBPAC materials and is available publicly, she wondered when the results from the Ebola 

pregnancy trials would be published. Pregnant women are very interested in safety data about 

this vaccine as is everyone else.

Dr. Douoguih indicated that these studies are ongoing. One of the studies that she mentioned 

earlier that is ongoing in Rwanda will randomize 2000 individuals. It is in the early phases of 

enrollment, so it will be some time before infant outcomes are available. Of course, they are 

very much committed to publishing as soon as they can. Within the context of the COVID-19 

program, they will make every effort to publish data, perhaps even in the interim. They will be 

conducting open label studies.
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

43

Dr. Romero pointed out that while he agrees with the acceptability as stated for key 

stakeholders, it is still important to have Indian Health Services (IHS) and other stakeholders 

from that group and their advisors weigh in on the acceptability of this vaccine for AI/AN.

Dr. Weiser (IHS) responded that he believes there is a place for this vaccine. Many people

already have mentioned cases and times where this vaccine would be more acceptable in terms 

of mass vaccination campaigns and logistics around easy distribution and administration in 

offices and clinics. Therefore, the IHS feels that this vaccine would be used and anticipates

using this vaccine in accordance with the other ACIP authorized vaccines.

Public Comment Overview

The floor was opened for public comment during the February 28-March 1, 2021 ACIP meeting 

at 2:30 PM ET. Given that many more individuals registered to make oral public comments than 

could be accommodated, selection was made randomly via a lottery. The comments made 

during the meeting are included here. Members of the public also were invited to submit written 

public comments to ACIP through the Federal eRulemaking Portal under Docket No. CDC2021-0021. Visit http://www.regulations.gov for access to the docket to submit comments or 

read background documents and comments received. 

Dorit Reiss, PhD, LLB

Professor of Law

University of California

Hastings College of Law

Thank you for the opportunity to comment. My name is Dorit Reiss. I’m a Professor of Law at 

the University of California Hastings College of Law. I’m grateful to the committee for all its 

work. I have three topics I want to address. First, your safety update today is about Johnson & 

Johnson. I’m looking forward to a more general one. These have been incredibly helpful. As 

you know, there are anti-vaccine activists online misrepresenting the data about COVID-19

vaccine to create or increase vaccine hesitancy. I know some of you also respond to that online. 

I want to thank the committee members personally for their measured, informed responses. We 

really appreciate that. Among other things, anti-vaccine activists are misusing Vaccine Adverse 

Event Reporting System (VAERS) reports in multiple ways and amplifying any harm after 

COVID-19, even if it’s unfounded and even if it’s against the facts. We can’t stop them from 

doing that, but you can help in responding to this. For example, when you provided the numbers 

on the benefits of influenza vaccine, even with limited effectiveness, it was a powerful and 

helpful counter to claims that it is useless. Short materials setting out, for example, death report

numbers in context, background race, causes, and why you conclude that there is no link to

vaccines for most of them would be helpful. Short material summaries on the complex safety 

data by Johnson & Johnson that you covered would be extremely helpful. Short materials about

VAERS reports and what they mean would be helpful. Although this is not the committee, if 

there is a way to add to every VAERS table generated explaining the reason that mentions the 

limits, that would also be helpful. My other two comments are about allocation. First, I hope you 

will consider the point made during your February 24-25 meeting about the need to prioritize 

incarcerated people. Up to this point, this population is being disproportionately impacted by 

COVID-19, is at high risk, and may be mistreated in distribution. When you incarcerate people, 

you take responsibility for their needs. ACIP discussed these people early on with long-term 

care facilities (LTCFs), but it is not reflected in the guidance. Maybe it’s time to revisit and 

redefine long-term care facilities to cover incarcerated people, for example, by redefining priority 

institutions as residential institutions for those who have limited ability to leave. They deserve an 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

44

opportunity to get vaccines if they want them. Finally, as mentioned in the last presentation, 

we’re seeing strong inequities in access to the vaccine. That is not on you. That is not your 

recommendation, but maybe it’s time to remind states that they need to prioritize high need 

populations and bring vaccines to where people are, including people who have less access to 

the internet-dependent channel or less mobility. That should be a priority. We need to protect 

everyone to end the pandemic. Thank you for your time.

Ms. Karen Ernst, MA, BA

Executive Director

Voices for Vaccines

Thank you. Hello ACIP members. My name is Karen Ernst and I am the Director of Voices for 

Vaccines. A year ago, I attended ACIP in person where Dr. Messonnier delivered an update on 

the SARS-CoV-2 and its spread overseas. At the time, there were 80,413 cases worldwide. 

Today, you are discussing the third vaccine approved by the Food and Drug Administration 

(FDA) under Emergency Use Authorization (EUA) to fight this virus. Thank you and thank

everybody who worked to get us here today. This single dose vaccine elicits a lot of hope. We 

all know that many people who need COVID vaccines the most are often having difficulty getting 

them. Some of this is simple supply and demand, some of it is distribution, and some of it is 

people gaming the system. My own parents were frustrated for weeks working within the system 

as we witnessed younger, healthier people cross state lines to access vaccine likely meant for 

others. An entire Vaccine Hunters Facebook group locally to me has 18,000 members and 190

posts today and works on the premise of finding vaccines via connections and rumors. We all 

know that these scenarios exacerbate health inequities. A single dose vaccine that can be 

stored in regular vaccine refrigerators has the potential to get more vaccines to Black, 

Indigenous, and People of Color (BIPOC); rural; and poor communities. I would get the Janssen 

vaccine in a heartbeat, but it has been billed as a less effective vaccine in the media already. If 

we put the single dose vaccine on a bus and drive it to places where people have had access 

issues with other vaccines, we risk the perception that the inferior vaccine is being saved for 

poor people, BIPOC communities, or rural folks. We need some real, plain language, clear 

public education on the difference between clinical trial efficacy and real-world effectiveness.

We need people to understand that the efficacy numbers put out were not on the same scale, 

like a standardized test, and we need people to have at the absolute best medicine and the best 

vaccines available to everyone in an equitable way. Without this work, we risk increasing not 

only vaccine hesitancy, but also distrust in healthcare for years to come. Thank you very much.

Ms. Amy Pisani, MS

Executive Director

Vaccinate Your Family

Good afternoon. My name is Amy Pisani and I’m honored to serve as the Executive Director of 

Vaccinate Your Family (VYF). Our organization was formed on the heels of a measles epidemic 

of ‘89 ’90 as Every Child By Two (ECBT). Our co-founders, former first lady Rosalynn Carter 

and Mrs. Betty Bumpers, knew that even 150 lives lost to a vaccine-preventable disease were 

too many and so they dedicated their lives to vaccine advocacy. We are proud to have been a 

part of the solutions that have resulted in a massive decline in vaccination disparities among 

children, although we recognize that we must continue to be vigilant and focus on ensuring that 

every child has access to life-saving vaccines. Thirty years later, we are renamed Vaccinate 

Your Family and are a part of the fight against a worldwide pandemic. On behalf of all of us, I 

wish to thank the committee and all of the staff at CDC for your unyielding commitment to 

stopping this deadly virus. I agree with the previous public comments with regard to the critical 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

45

importance of transparency in the review of the safety data for COVID-19 vaccines, both preand post-authorization. This intense review and the sharing of safety data is of paramount 

importance to help advocacy organizations like ours as we prepare resources that may help 

increase not only confidence in vaccinations, but also COVID-19 vaccine readiness, particularly 

among minority communities. I also wish to thank the members of the National Academy of 

Medicine (NAM) and the ACIP Work Group for the diligent work you conducted to not only 

research disproportionate burden of coronavirus on various communities and ethnic 

populations, but also to develop the prioritization plans. Not all states chose to follow the plans. I 

can tell you that based on the calls that flooded into our organization on phone and email lines,

particularly in the early weeks, that the overwhelming majority of calls were received from 

seniors desperately searching for COVID-19 vaccinations came from states that failed to follow 

your prioritization scheme. Confusion and chaos in those states was real and we hope that 

when the pandemic is behind us, government agencies and legislators will conduct a 

postpartum analysis to determine which prioritization plans resulted in reduced cases and 

overall public health functionality. Here at Vaccinate Your Family, we paid close attention not 

only to the morbidity and mortality data, but also to the plan and we redoubled our efforts to 

eliminate immunization disparities, particularly among communities of color. In December, we

proudly announce our partnership with the National Council of Negro Women (NCNW) to create 

the Good Health Women’s Immunizations Network (Good Health WINs), which will begin in 10 

states where we will create a network of African-American women who will become COVID

vaccine allies, encouraging their local communities to vaccinate against this deadly disease. We

have also set our sights on developing new culturally competent resources and videos featuring 

experts in many languages and we’re translating our website into Spanish. We are also 

translating a large portion of our resources into over 6 languages. We wish to thank you so very 

much for everything you’re doing. We know that everyone on this committee is committed to our 

shared mission to save lives. We look forward to working with you now and into the future.

Jeffrey Silberzweig, MD

Chief Medical Officer

The Rogosin Institute

Good afternoon. Thank you for the opportunity to address ACIP today. I am Jeffrey Silberzweig, 

Chief Medical Officer of the Rogosin Institute in New York City (NYC). We are a non-profit 

provider of kidney care, including dialysis to some 1500 patients. I speak today on behalf of my 

colleagues, the 21,000 members of the American Society of Nephrology (ASN), whose COVID19 Response Team I have Co-Chaired for the past year, and dialysis providers large and small

for-profit and non-profit across the United States. Most importantly, I speak on behalf of the 

500,000 Americans with chronic kidney disease (CKD) who depend on life-sustaining dialysis 

treatments. By virtue of their primary condition and the invasive nature of their ongoing regular 

care, these individuals when infected with SARS-CoV-2, are at higher risk of serious COVID

requiring hospitalization and of more mortality than age-matched Medicare beneficiaries.

Dialysis patients must go out into the community 3 times weekly for 4 to 6 hours in each time.

They do not have the option of sheltering at home, increasing their risk and the risk of those in 

their family and community. Patients with chronic kidney disease are disproportionately AfricanAmerican, Hispanic, and Native American. They experience the effects of lifelong health 

disparities, heightening their susceptibility. Data show that they have a higher risk of acquiring 

COVID and of more severe complications from it due to their multiple comorbid medical 

conditions. In the US and around the world, mortality rates of dialysis patients with COVID range 

from 20% to 40%. The dialysis community has committed to working together to ensure that 

patients and staff get vaccinated if vaccines are allocated. Because our patients are treated 3

times weekly, administration of the second dose is less problematic than in most patients.
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

46

Because of the long-standing trusted relationship between dialysis patients in the staff who care 

for them, we have consistently had high rates of vaccination against infectious diseases, like 

influenza and hepatitis B. Our patients are less likely to be able to register online for vaccine 

appointments because of their medical and socio-economic conditions, and are less likely to be 

able to wait in line for vaccinations. I do not envy the responsibility you carry in recommending 

who merits priority for vaccination, but I ask that you consider that dialysis patients are like 

daytime congregate care facility patients with similar mortality and should be prioritized like 

residents of long-term care facilities. They are among the highest risk groups of dying from

COVID. I beseech you to provide an allocation of 500,000 doses of vaccine to allow dialysis 

providers to protect these mostly Black and Brown patients. Thank you for your time today.

Albert Faro, MD

Vice President, Clinical Affairs

Cystic Fibrosis Foundation

Good afternoon. My name is Dr. Albert Faro and I’m the Vice President of Clinical Affairs at the 

Cystic Fibrosis Foundation (CF Foundation). On behalf of the foundation and the more than 

30,000 people with CF in the United States, I would like to thank the committee for the 

opportunity to provide comments regarding development and allocation of COVID-19 vaccines. 

The CF Foundation is a national organization actively engaged in research and development of 

new therapies for CF, a rare life-threatening genetic disease characterized by thick, sticky 

mucus in the lungs resulting in frequent acute and chronic respiratory infections. These chronic 

airway infections are punctuated by pulmonary exacerbations—events often triggered by 

respiratory viral infections that are a risk factor for an irreversible decline of lung function and 

associated with morbidity and mortality. Continued progression of the disease can result in 

advanced lung disease so severe that lung transplantation may be the only life-extending 

option. COVID-19 represents a serious threat for people with CF. The CF Foundation Patient 

Registry collects information on the health status of people with cystic fibrosis who receive care

in CF Foundation-accredited care centers. The data underscores the threat this infection poses 

to people with CF. A published global analysis of 181 COVID-19 cases among people with CF

demonstrated that CF patients with advanced lung disease and those who are post-lung 

transplant are at increased risk of severe outcomes, including death. We recognize that to date,

the ACIP included those with high-risk conditions as a prioritized group in the committee’s 

COVID-19 vaccine allocation recommendations, and we are pleased that these 

recommendations are accompanied by language from the CDC about using individuals clinical 

judgment to identify patients whose risk factors warrant priority vaccine access. However, we 

are deeply concerned about the wide range of interpretations of ACIP’s recommendations 

among states and localities, in some cases not including rare diseases like CF on lists of 

prioritized populations and in other cases, opting to use age-based criteria alone. The desire for 

simplicity must not come at the expense of those who are most vulnerable to the consequences 

of this infection. People with CF and others with high-risk conditions must be prioritized for early 

access. Some current state and local practices run counter to ACIP’s intent of prioritizing those 

at highest risk of morbidity and mortality and are placing people with CF and other underlying 

medical conditions at greater risk, solely for the sake of expediency. We urge the ACIP to 

provide clarifying language on Phase 1c recommendations for rare disease populations to 

ensure that high-risk patients with diseases like CF are able to gain early Access to COVID-19 

vaccines. Thank you again for your attention and consideration of people with CF as you tackle 

these critical issues. 
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Jonathan Brand, JD

President

Cornell College

Thank you. My name is Jonathan Brand. I am President of Cornell College in Mount Vernon, 

Iowa. I’d like to offer an idea of using the 1 shot Janssen vaccine right now to target a 

population that as a group moves around the most—the 53 million 18 to 29 year old population,

which includes college and university students. In fact, at over 30 million, 18 to 24 year olds are 

also a group highly likely to live in congregate settings, residence halls, and apartments—an 

environment that greatly increases spread. A strategy that relies on colleges and universities to 

vaccinate all 18 to 29 year olds, not just our students, could jumpstart a second front against 

COVID. Vaccinating those ages 18 to 29, some of our biggest spreaders, will dramatically 

accelerate reaching herd immunity. In addition, colleges and universities can be set up as mass 

vaccination sites, inoculating thousands of individuals in this cohort in short order rather than 

further taxing current mass vaccination sites. We have the gyms, the arenas, the field houses, 

the parking lots. Because schools of higher education are located all over the country in urban,

suburban, and rural settings, we can increase access. We are everywhere. Fortunately, the 

Janssen vaccine does not need special cold storage. Because it’s a 1 shot deal, this vaccine 

resolves a logistical challenge we’ll soon confront—a group that tends to relocate throughout the 

country in May or June and won’t be able to easily return to the same location or state for a 

second shot. Finally, because about 45% of those ages 18 to 24 work in retail and leisure 

hospitality industries where we’ve been concerned with COVID transmission and the harmful 

economic impact of COVID, this vaccination strategy can only help to jumpstart those sectors as 

we return to normalcy. Some believe my idea would encourage reckless behavior postvaccination. I don’t believe that. I’m not seeing 20 year olds at bars and restaurants any more 

than older populations. At Cornell, we currently have a 0% student positivity rate and 

cumulatively 1.6% because our students, like so many others, are willing to sacrifice. I am 

confident that this will continue until you tell us we can relax our protocols. States should 

continue their current phases with Pfizer and Moderna, but they should plan to concurrently

mass vaccinate all 18 to 29 year olds with the Janssen vaccine. Higher education can help get 

this done now. Thank you.

Mr. Eugene Jackson, III

NxStage

My name is Eugene Jackson and I am currently a dialysis patient in Waco, Texas. I want to 

thank you for giving me the opportunity to give my voice. I am an African American male and I 

work in the African American community as well as the dialysis community. We now understand 

that African-Americans and Hispanics are disproportionately being affected by COVID-19. 

African Americans are 1.9% more likely to have COVID-19 and Hispanics are 2.3% more likely 

to be affected by COVID-19. Our communities have been ravaged by this dreaded disease and 

the only way to receive protection is by vaccination. I appreciate the effort to be vaccinated, but 

also it seems to me that we seem to be further down the line to be vaccinated. If we are such a 

high risk, it would seem to me that we should be more likely to be one of the first ones to be 

vaccinated. I understand that it’s up to each state to disseminate the vaccinations as you see fit, 

but I just wanted to get an understanding of why it is that those who have such morbidity 

conditions seem to be so far down the line. If we know that we are so disproportionately affected 

by this dreaded disease, why are we so haphazardly down the line to be vaccinated? I 

appreciate the effort that has come about from the CDC and the ACIP to get the vaccines out,

but I just hope that in the future, these people become more of a priority. Thank you.
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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Michelle Fiscus, MD, FAAP

Board Certified Pediatrician

Medical Director

Vaccine-Preventable Diseases and Immunization Program

Tennessee Department of Health

Good afternoon. I’m Dr. Michelle Fiscus. I am the Medical Director of Tennessee’s VaccinePreventable Diseases and Immunization Program. I’m also a Board Certified Pediatrician. I'd 

like to thank the committee for all its work during this challenging time. The work you do has 

never been more important to the health of this nation. We all owe you a debt of gratitude for 

sacrificing your time to ensure that the COVID-19 vaccines that have been granted emergency

use authorization are administered based upon sound research and science. It’s easy to lose 

sight of the tremendous magnitude of this pandemic, which is far and away the most significant 

infectious event ever to impact the world in more than a century. It has justifiably impacted every 

aspect of our lives. More than half a million Americans are dead—41 times the number of lives 

lost during the 2009 H1N1 pandemic. More than 28 million, nearly 1 in 11 of us, have been 

affected by the SARS-CoV-2 virus with 13% of the cases in children. That amounts to 1 out of 

every 25 children in the United States having been infected with this virus, the long-term 

outcomes of which are still unknown. It is likely reasonable to assume that the more than 2000 

children who have gone on to develop multi-system inflammatory syndrome children, or MIS-C, 

will have their lives shortened by this disease. Early studies have indicated that more than half 

of these children suffer heart damage, 70% suffer acute kidney injury, and many require 

dialysis. While it’s true that children tend not to die from acute COVID-19, how many more 

children will suffer the chronic effects of this disease? Yet, children will be the last to be 

vaccinated, in part due to their lower risk of acute morbidity and mortality, but most importantly 

due to the lack of an authorized vaccine. It is critically important that the vaccine manufacturers 

make progress in pediatric COVID-19 vaccine trials as quickly as possible not only to prevent 

infections, but to achieve herd immunity. As children comprise nearly a quarter of the US 

population, being able to vaccinate children against SARS-CoV-2 is crucial to our ability to 

achieve herd immunity in this country. In the meantime, we need every qualified individual to 

say “yes” when offered a COVID-19 vaccine, no matter the vaccine, and do their part to end this 

pandemic. We need to work tirelessly to earn the trust of those who are hesitant, especially our 

Black and Hispanic brothers and sisters, so that these populations that have been 

disproportionately impacted by COVID-19 will also accept this truly remarkable opportunity to 

protect themselves, their loved ones, and their communities against this terrible infection. Thank 

you again for your dedication to this work.

Mr. Ben D'Avanzo, MPA

Senior Health Policy Analyst

National Immigration Law Center

Thank you. My name is Ben D'Avanzo. I appreciate the committee members for your service. I 

am the Senior Health Policy Analyst with the National Immigration Law Center (NILC). We are 

the primary advocacy organization working on behalf of low-income immigrants, particularly 

engaging on health and benefits issues. We have a long history of working to protect the health 

rights of immigrants, including through a network of community legal advocacy organizations. 

There are over 22 million non-citizens living in the US and they’ve been disproportionately 

serving on the front lines of this pandemic. The ACIP and CDC have worked hard to prioritize 

different populations based on risk factors, such as being frontline workers. Yet, being eligible 

for vaccine is not much use if you face deep barriers to accessing it. We have seen from our 

partners and media reporting that many immigrants face numerous barriers to accessing the 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

49

vaccine. Because many communities of color have high rates of foreign-born individuals, we 

cannot address racial equity without addressing immigrants. I want to address a few of those 

barriers that this committee can play a role in addressing. First, we did send comments to the 

committee. In your December meeting, there were concerns immigrant-heavy industries like 

food and agriculture production may be left out of state definitions of essential workers. These 

can be isolating places to work that have seen many outbreaks, like meat packing plants, and 

also has workers in congregate settings. Workers may be unaware of their eligibility for vaccine, 

even if they are technically included in that definition. We are also very concerned about 

attempts to ask that immigrants bring in identification documents. Many immigrants, particularly 

low-income ones, lack such documents. Well-intentioned efforts that require proof of residency, 

place of work, or medical status may exclude those communities. Asking for an email harms 

those who are less educated or have low technology literacy, and asking for Social Security 

Numbers (SSNs) for the uninsured deters many from getting the vaccine. If the goal is to get as 

many shots in arms and to as many higher risk populations as possible, we should not be 

creating barriers. We need clear standards to vaccine-providing entities and states that they 

cannot prioritize anyone based on their immigration status, which we have seen both political 

leaders declare intentions to do and providers denying people because they are undocumented. 

These events are spread by social media and by the news and can overpower important 

messages coming from public health officials about the vaccine to communities. We must 

provide clear information in as many languages as possible to immigrants about the availability 

of the vaccine, the fact that their immigration status does not preclude them from getting it, and 

the fact that their data is safe. Thank you very much.

Vote: Janssen COVID-19 vaccine

Sara Oliver, MD

LCDR, U.S. Public Health Service

Co-lead, Advisory Committee for Immunization Practices COVID-19 Vaccines WG

COVID-19 Response

Centers for Disease Control and Prevention

Dr. Oliver reminded everyone that the policy question considered by the WG was, “Should 

vaccination with the Janssen COVID-19 vaccine (1-dose, IM) be recommended for persons 18 

years of age and older under an emergency use authorization?” he WG interpretation was that 

the desirable consequences clearly outweigh undesirable consequences in most settings. 

Therefore, the WG recommended the vaccine and proposed the following interim 

recommendation language:

“The Janssen COVID-19 vaccine is recommended for persons 18 years of age and older 

in the U.S. population under the FDA’s Emergency Use Authorization.”
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50

Motion/Vote: Janssen COVID-19 Vaccine

Dr. Poehling made a motion to accept the proposed language for an ACIP vote on the interim 

recommendation for use of the Janssen vaccine as presented, “ he Janssen COVID-19 vaccine 

is recommended for persons 18 years of age and older in the U.S. population under the FDA’s 

Emergency Use Authorization.” Dr. Lee seconded the motion. Dr. Chen recused himself from 

the vote due to a potential COI. The motion carried with 12 affirmative votes, 0 negative votes, 

and 1 abstentions. The disposition of the vote was as follows:

12 Favored: Bahta, Bell, Bernstein, Daley, Kotton, Lee, Long, McNally, Poehling, Romero, 

Sanchez, Talbot

 0 Opposed: N/A

 1 Abstained: Chen

 2 Absent: Ault, Frey

Discussion Points

Ms. McNally inquired as to whether V-SAFE would be adapted to accommodate the Janssen 

vaccine.

Dr. Cohn indicated that recipients of the Janssen vaccine could enroll in V-SAFE the same as 

for the other two recommended vaccines.

Reflecting on Dr. Bell’s introductory comments and the scope of the tragedy, Dr. Daley stressed 

that in the midst of this tragedy, there was some reason for optimism. A very common greeting 

in the world has been, “Have you eaten today?” hat is reflecting a fundamental human need. 

Now the most common greeting is, “Have you gotten vaccinated?” People are intensely 

concerned about where they are on the prioritization list, and that has been very complicated. 

People want to get vaccinated as soon as possible to protect themselves and their families. In 

many ways this may be an obvious point, but he said he wanted to state explicitly how very 

grateful he is that there are now 3 safe and highly effective vaccines and remind everyone that if 

they use all supplies of all 3 vaccines, then everyone essentially moves up on whatever 

prioritization list they are on. For that, he thought everyone should be very grateful.

Dr. Lee expressed appreciation for Dr. Daley’s comments and reiterated that the life expectancy 

overall has decreased by 1 full year. However, life expectancy has decreased disproportionately 

for Black populations by 2.7 years and Hispanic populations 1.9 years. In parallel, there 

continue to be challenges with regard to equity, access, and the substantial variability that 

continues to occur by state and county. Those numbers mean to her that it is imperative to 

continue to ensure that equity is at the forefront of how vaccines are implemented and that this 

must be done systematically. The disproportionate difference in life expectancy is not specific by 

age. It really reflects the overall burden of disease in the population. She recognized all of the 

implementation challenges that occur, but emphasized that it would behoove them all at the 

national, state, local, and practice levels to continue to be vigilant in trying to keep equity at the 

forefront.
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

51

Dr. Romero thanked all of the members of the ACIP COVID-19 Vaccine WG for the work that 

they engaged in to bring forward this vote, as well as the voting members and liaisons for giving 

up all of their time on the weekend. He recognized that this is a very heavy and intense 

schedule that cuts into personal time and time with everyone’s families.

Introduction

Beth Bell, MD, MPH 

ACIP, COVID-19 Vaccine WG Chair

Clinical Professor, Department of Global Health

School of Public Health, University of Washington 

Dr. Bell introduced the session, indicating that the agenda for the day would include 

presentations on the following topics:

❑ Implementation Considerations for COVID-19 Vaccines

❑ Clinical Considerations for Use of COVID-19 Vaccines

❑ Vaccine Safety Technical Subgroup (VaST) Introduction

❑ COVID-19 Vaccine Safety Update

❑ VaST Assessment of Safety Data

❑ Emerging SARS-CoV-2 variants

Implementation Considerations for COVID-19 Vaccines

Kathleen Dooling, MD MPH

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention

Dr. Dooling presented on implementation considerations for the Janssen COVID-19 vaccine

specifically, COVID-19 vaccine prioritization, and dosing intervals for mRNA vaccines. In a 

unanimous vote to recommend the Janssen COVID-19 vaccine on February 28, 2021, ACIP 

stated no preference for any of the 3 authorized vaccines. The vaccines were not studied in 

head-to-head trials. Therefore, the results of the Janssen Phase III trial are not directly 

comparable with the messenger ribonucleic acid (mRNA) vaccines. Janssen’s COVID-19 

vaccine was studied at a different calendar time and under different geographical 

circumstances, which led to difference in the circulating SARS-CoV-2 variants and a higher 

background incidence during their study. The Janssen vaccine demonstrates strong protection 

against severe COVID-19, with 93% VE against hospitalizations with 2 cases in the vaccinated 

compared with 29 cases in the placebo. Moreover, there were no COVID-associated deaths in 

vaccinated group versus 7 in the placebo group.

Given that the Janssen COVID-19 vaccine has been authorized for emergency use by the FDA 

and recommended by the ACIP, consideration can be given to how this vaccine best fits into the 

national COVID vaccination program. The characteristics of this vaccine are that it is a 1-dose 

regimen and may be transported and stored at 2

o

to 8

oC for up to 3 months. It requires no 

diluent or reconstitution at the point of use. In terms of where the Janssen COVID-19 vaccine

Coronavirus Disease 2019 (COVID-19) Vaccines: March 1, 2021
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

52

may best fit into a vaccination program, jurisdictions may consider use in places such as mobile

or pop-up clinics, newly established vaccine administration sites, and sites that do not have 

freezer capacity such as in most adult healthcare provider (HCP) offices. It should be noted that 

that the type of vaccine available at any given appointment should be transparent to the 

consumer. Recipients of this vaccine might include people who want to be fully vaccinated 

quickly, people who do not want to return or cannot return for a second dose, and mobile 

populations or homebound populations.

Ultimately, the WG thought that during a pandemic and under an EUA, offering Janssen 

COVID-19 vaccine to persons 18 years of age and older, according to established allocation 

and eligibility recommendations in a given jurisdiction, is an effective implementation strategy. 

This approach allows for jurisdictional flexibility, supports rapid vaccination and increases in 

population immunity, does not single out any particular group, and allows individuals to be 

vaccinated with the earliest vaccine available.

Regarding vaccine prioritization, the original goals of the COVID-19 Vaccine Program were to: 

1) ensure the safety and effectiveness of COVID-19 vaccines; 2) reduce transmission, 

morbidity, and mortality of COVID-19 disease; 3) help minimize disruption to society and the 

economy, including maintaining healthcare capacity; and 4) ensure equity in vaccine allocation 

and distribution. As of February 27, 2021, more than 72 million doses of COVID-19 vaccine 

have been administered in the US. However, jurisdictions continue to face constrained supplies 

and continued reliance on large vaccination centers. Most jurisdictions are in Phase 1b or 

expanding into Phase 1c, and most states have made modifications to the ACIP prioritization 

framework26. These modifications include either sub-prioritization or delayed vaccination of 

essential workers, adding eligibility age bands for people younger than 65 years of age, and 

sub-prioritization of high-risk medical conditions or requiring ≥2 conditions. Looking forward 

toward the next several weeks, vaccine manufacturers have made specific commitments by the 

end of March 202127. Pfizer has indicated that they will produce 120 million doses, Moderna

committed to 100 million doses, and Janssen committed to 20 million doses. The fulfillment of 

these commitments will result in a significant increase in available vaccines compared to prior 

months.

Even with increased vaccine supply, a number of implementation challenges remain. There are 

a number of responses jurisdictions may consider to meet those challenges. First, adjudicating

eligibility in large vaccination centers, particularly on the basis of essential worker status or highrisk medical conditions, can be difficult and time-consuming. It should be noted that verification 

of eligibility should not hamper throughput at large vaccination clinics. Medical care homes or 

PCPs may be better able to assess eligibility on the basis of underlying medical conditions. 

Another challenge is implementing the list of high-risk conditions. The CDC list relies on 

published studies and is not exhaustive. Certain conditions on the list encompass a wide range 

of severity. Therefore, clinical judgement may determine if rare conditions not on the list confer 

increased risk of severe COVID-19.

Another challenge is that the size of the eligible groups in Phase 1c may exceed vaccine supply. 

Jurisdictions may consider the addition of eligibility age bands for people younger than 65 years 

of age (e.g., 60-64 or 55-64 or 50-64) as supply permits. This may be particularly helpful in large 

vaccination settings. Jurisdictions also may consider prioritizing people with ≥2 high-risk 

conditions. Transmission in congregate settings (e.g., prisons, homeless shelters, or LTCFs)

26 https://energycommerce.house.gov/committee-activity/hearings/hearing-on-pathway-to-protection-expanding-availability-of-covid19

27 https://www.kff.org/other/state-indicator/state-covid-19-vaccine-priority populations 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

53

continues to be a challenge. Jurisdictions may consider offering vaccine to all unvaccinated staff 

and residents at the same time without waiting for eligibility of each individual group.

Another major challenge is promoting heath equity while ensuring efficient vaccine distribution 

and administration. Some strategies jurisdictions can use to improve equitable vaccine 

distribution include: 1) using a SVI or other needs-based indexes to place vaccine clinics; 2) 

partnering with FQHCs such that they can be vaccination hubs and help to register eligible 

community members for vaccination; or 3) offering the Janssen COVID-19 vaccine as an option 

for populations for whom returning for a second dose would be difficult. Of course, community 

engagement and education will be important as new COVID-19 vaccines are authorized and 

recommended for use.

In terms of dosing intervals for mRNA vaccines, there are two issues. The first issue regards the 

potential risks and benefits of delaying the second dose of an mRNA vaccine. The second issue 

arises around the potential for a single dose of an mRNA vaccine for individuals with confirmed 

prior SARS-CoV-2 infection. As background for the issue of delaying the second dose, extended 

inter-dose intervals have been adopted by other national vaccine advisory groups and proposed 

by individuals in the US as a strategy to increase 1-dose coverage during a time when demand 

exceeds supply. Note that the current CDC guidance is that, “The second dose should be 

administered as close to the recommended interval as possible. However, if it is not feasible to 

adhere to the recommended interval, the second dose of Pfizer-BioNTech and Moderna 

COVID-19 vaccines may be scheduled for administration up to 6 weeks (42 days) after the first 

dose.”

28

With respect to delaying the second dose, in Phase I/II clinical trials, neutralizing antibodies did 

not show large increases until after receipt of the second dose. In Phase III trials, about 97% to 

98% of recipients received both doses on schedule, which makes the study of prolonged 

intervals almost impossible with these data. The 1-dose VE estimates from those trials are 

between 50% to 90% and are higher when the follow-up time considered is that which happens 

at least 2 weeks after the first dose, thereby making the follow-up under study very short. There 

have been a number of early studies of real-world effectiveness of 1 dose of the vaccine. A 

matched case-control study in Israel29 found effectiveness of a single dose preventing 

hospitalization to be 78% between 21 to 27 days post-dose 1. A prospective cohort study in 

Scotland30 also found 1 dose to prevent hospitalization and found that VE reached a high of 

85% 28 to 34 days post-dose 1, followed by a slight decline after that. It should be noted that 

the group with longer follow-up in that study had a higher proportion of older people.

In terms of the pros and cons of delaying the second dose, the pros are that this strategy could 

provide 1 dose protection to a larger number of people over the next several months. If 1 dose 

protection is high and persists, this could prevent more infections and deaths31. Most experts 

expect that boosting from the second dose is still likely to be effective, even at a longer interval. 

As for cons, lower neutralization antibodies could be protective against “wild-type” COVID-19, 

28 https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html

29 Dagan N, et al. NEJM, 2021 

30 Vasileiou E, et al. Lancet, preprint 2021

31 Accelerate COVID-19 Vaccine Rollout by Delaying the Second Dose of mRNA Vaccines https://doi.org/10.1093/cid/ciab068; The 

effectiveness of the first dose of BNT162b2 vaccine in reducing SARS-CoV-2 infection 13-24 days after immunization: real-world 

evidence | medRxiv
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

54

but not novel variants32-33-34.1-dose vaccination could leave individuals susceptible to variants, 

providing selective pressure and increased transmission of variants35. The estimates of effect 

for a single dose are imprecise and duration of protection after the first dose is unknown.

Additionally, a prolonged interval would contradict FDA’s EUA for a vaccine platform for which 

there is minimal experience.

In summary, the majority of WG members thought that there currently are insufficient data to 

increase recommended intervals and that there is important uncertainty regarding protection 

from the variants following 1 dose of mRNA COVID-19 vaccines. The next steps on this issue 

are to continue to monitor post-authorization effectiveness studies. Any updates to vaccine 

recommendations will be evidence-based, discussed publicly, and made in collaboration with

the FDA.

Moving on to the question of a single dose of mRNA vaccine for individuals with confirmed prior 

SARS-CoV-2 infection, by way of background, there have been anecdotal reports of increased 

reactogenicity following vaccination among people with prior COVID-19. Additionally, recent

published reports suggest high antibody response after 1 dose for individuals with prior SARSCoV-2 infection. The current CDC guidance36 states, “...while vaccine supply remains limited, 

persons with recent documented acute SARS-CoV-2 infection may choose to temporarily delay 

vaccination, if desired, recognizing that the risk of reinfection, and therefore the need for 

vaccination, might increase with time following initial infection.”

Immunogenicity following vaccination among persons with prior SARS-CoV-2 infection was 

evaluated in 2 studies published in pre-print. Both studies assessed antibody titers after 1 dose 

in seropositive compared to seronegative individuals. Both studies showed higher antibody titers 

in seropositive individuals compared to seronegative individuals after 1 dose37,

38. One available 

pre-print study evaluated reactogenicity following mRNA vaccination in seropositive and 

seronegative persons39. This study found that localized injection site symptoms occurred with 

similar frequency between the two groups; however, systemic side effects occurred at higher 

frequency among individuals with pre-existing immunity. The reactogenicity was similar to 

symptoms reported for the second dose for people who did not have pre-existing immunity in 

the Phase 3 trials.

To summarize the pros and cons for the question of a single dose of mRNA vaccine for 

individuals with confirmed prior SARS-CoV-2 infection, the pros are that this strategy could free 

up second doses from seropositive persons to be provided to seronegative persons and that 

seropositive persons would not receive 2 doses of reactogenic vaccine. The cons are that 

current studies included individuals with confirmed antibodies to SARS-CoV-2. Not everyone 

with prior infection still has detectable antibodies and performing large-scale antibody screening 

prior to vaccination is not feasible. Also, correlates of protection are currently unknown. 

32 Increased resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 to antibody neutralization. 2021.01.25.428137v2.full.pdf 

(biorxiv.org)

333SARS-CoV-2 variant B.1.17 is susceptible to neutralizing antibodies elicited by ancestral Spike vaccines Microsoft Word -

Shen_B117_ver10.docx (biorxiv.org)

34 4The E484K mutation in the SARS-CoV-2 spike protein reduces but does not abolish neutralizing activity of human convalescent 

and post-vaccination sera | medRxiv

35 Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimens 

https://doi.org/10.1101/2021.02.01.21250944

36 https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html

37 Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 

mRNA vaccine | medRxiv

38 Single Dose Vaccination in Healthcare Workers Previously Infected with SARS-CoV-2 | medRxiv

39 Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 

mRNA vaccine | medRxiv
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

55

Therefore, it is not possible to extrapolate antibody studies directly to VE. In addition, there are 

currently only limited data and small studies and a single dose would contradict the FDA’s 

evidence-based EUA for a vaccine platform for which there is minimal experience.

In summary, the majority of WG members thought that there are currently insufficient data to 

support changes to guidance or recommendations. The WG did feel that this is an important 

area to pursue further data in the coming weeks and months, and that jurisdictions could 

consider promotion of the existing guidance that those with prior infection may choose to 

temporarily delay vaccination for several months. The next steps are to collect and review 

further data on safety and reactogenicity, as well as immunogenicity and effectiveness of 

COVID-19 vaccines among individuals with prior infection. Any updates to the vaccine 

recommendations will be evidence-based, discussed publicly, and made in collaboration with

the FDA.

In closing, Dr. Dooling posed the following questions for ACIP consideration and deliberation 

during the discussion period:

Janssen COVID-19 Vaccine

❑ Do you agree that offering Janssen COVID-19 vaccine to persons 18 years and older, 

according to established allocation and eligibility recommendations, is an effective 

implementation strategy?

Vaccination Prioritization

❑ What are the key challenges and opportunities of implementation guidance options for:

1. Additional age eligibility brackets <65 years

2. Eligibility based on 2 or more high risk conditions

mRNA Vaccine Dosing

❑ What additional data are needed to inform:

1. Delay the second dose?

2. Single dose of mRNA vaccine for individuals with confirmed prior SARS-CoV-2 

infection?

Discussion Points

Janssen COVID-19 Vaccine: Do you agree that offering Janssen COVID-19 vaccine to 

persons 18 years and older, according to established allocation and eligibility 

recommendations, is an effective implementation strategy?

In terms of whether the Janssen COVID-19 vaccine is an effective strategy, Dr. Bernstein 

inquired as to whether there are data on the effectiveness of the implementation strategy with 

the two mRNA vaccines. When the phases were developed, there were 3 million LTCF 

residents and that discussion included giving the vaccine to the staff in the LTCFs. It was 

mentioned the previous day that although there are 3 million LTCF residents, 7 million doses 

have been administered in LTCFs.

Dr. Dooling indicated that evaluation of the implementation strategies is currently ongoing in a 

number of ways. Slide 30 includes more details on at least the procedural outcomes of how 

many doses have been delivered. More than 48 million people have been vaccinated with 1 or 

more doses, which accounts for approximately 19% of the US adult population 18 years of age 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

56

and older. Of the 7 million doses administered in LTCF, which were considered a priority in 

Phase 1a, over 1.5 million doses have been administered to LTCF staff.

Dr. Messonnier added that this is perhaps a larger topic than the time allotted during this 

meeting and that it is important to assess the safety and effectiveness of both the vaccines and 

vaccine strategies. There are a variety and series of studies that they can come back to the 

ACIP with that are evaluating the short-term effectiveness and duration of protection. 

Specifically, there is work now within CDC looking at the impact of the vaccine in LTCFs in 

which they are trying to disentangle the effect of vaccination and the effect of other mitigation 

measures. Similarly, there are studies ongoing to assess the effectiveness of the strategies 

among healthcare workers (HCW).

Dr. Kotton said that in thinking about where the new Janssen vaccine would be used, she would 

encourage enrichment and enhancement of the comorbidity list. It appeared that the list was 

suggesting that this could be determined by physicians, but she did not think this would be a 

realistic aspect. It would be helpful to have better guidance regarding the comorbidities, given 

that many states are relying on this list.

Dr. Messonnier acknowledged that this is a valid point that is under active discussion. There are 

many issues on which ACIP could provide helpful input, but in the limited time available they 

would like the members to focus on the Janssen vaccine and how to specifically alter, modify, or 

target Janssen’s vaccine.

When discussing eligibility for the Janssen vaccine, Ms. Stinchfield (NAPNAP) suggested also

mentioning those for whom the vaccine would be contraindicated.

Dr. Dooling indicated that CDC is not aware of any contraindications and the FDA information 

does not include any specific contraindication outside of an allergic reaction to any of the 

vaccine components.

Dr. Long agreed with the WG’s interpretation that this is not an inferior vaccine and instead of 

talking about who should not receive it, they should talk about how to further the desire to 

immunize all people by particularly discussing targeting the use of this vaccine. It could and 

should be prioritized to what are perceived to be difficult-to-reach populations (e.g., homeless,

those without access to transportation, people who cannot take off of work for 2 doses without 

losing income, those who do not have easy access to the internet to get appointments easily) 

and how to best do this without causing more unworkable recommendations. They should give 

guidance to further the goal to increase more people and decrease inequity. She is convinced 

by the data shown that this vaccine is comparable to the others and this one can be given in 1 

dose.

Dr. Daley felt that there were some negatives to separating the Janssen vaccine out (e.g., less 

value, would give local jurisdictions less flexibility, would be less efficient as a delivery strategy, 

and is less evidence-based). He agreed with and supported the statement that “offering 

Janssen COVID-19 vaccine to persons 18 years and older, according to established allocation 

and eligibility recommendations, is an effective implementation strategy.”
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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Dr. Hahn (CSTE) indicated that the National Governors Association (NGA) and Kaiser Family 

Foundation (KFF) both have updated tables state-by-state:

→ https://www.nga.org/wp-content/uploads/2021/02/State-Phased-VaccineDistribution_2.17.pdf 

→ KFF, updated as of 2/22: https://www.kff.org/report-section/state-covid-19-data-andpolicy-actions-policy-actions/

In terms of implementation guidance, Dr. Sonja Hutchins expressed concern that if ACIP/CDC 

state that the Janssen vaccine should be used in mobile clinics, for certain populations or 

communities considered hard-to-reach, this may introduce a level of mistrust because it is a 

single dose vaccine and might lead to increased hesitancy. Therefore, she did not support 

targeting mobile clinics. Those who have run mobile clinics for vaccination know that they can 

return to those communities to give another dose. They must be very careful to understand what 

might be some of the unintended consequences of targeting communities of color, who some 

may think are hard-to-reach when they are reachable.

Dr. Fryhofer (AMA) said that speaking as a practicing general internist, she has a lot of 

immunocompromised patients. They do not recommend live attenuated influenza vaccine 

(LAIV) as a first line for these patients. In terms of thinking about who to give this vaccine to now

that there are two different platforms, she wondered whether additional thought should be given 

to immunocompromised patients. There is good experience using the Janssen platform and the 

company shared the previous day that they have given this vaccine platform to over 193,000 

people, including pregnant women, children, and infants. However, when ACIP asked about the 

specifics of giving this vaccine during pregnancy, the manufacturer indicated that these data 

have not been published. She wondered at this time whether they felt totally comfortable giving 

a viral vaccine to immunocompromised patients.

Dr. Dooling reiterated that being immunocompromised is not a contraindication to this vaccine. 

The vaccine itself is not considered live as it is not capable of replication, which differentiates if 

from live vaccines.

Ms. Bahta indicated that she is very much in support of moving forward using the established 

allocation and eligibility recommendations for the Janssen vaccine. She believes that states and 

local jurisdictions appreciate the nimbleness that this vaccine provides and it really should not 

have preference of one over another, given the potential for unintended consequences or 

sending an indirect message that it is not equivalent. It is a very nimble vaccine that is very 

helpful for the response.

Dr. Lee stated her agreement that for Question 1, the Janssen vaccine should be offered as an 

equivalent to other available vaccines to protect against COVID. In terms of clarifying questions, 

there is extreme variability in the way allocations are done state-by-state and sometimes 

county-by-county. She called upon the American College of Obstetricians and Gynecologists 

(ACOG) to comment on whether there are any difference in the ability to offer vaccine,

particularly the Janssen vaccine, to pregnant women who wish to be vaccinated if, for example, 

an mRNA vaccine is not available.

Dr. Eckert (ACOG) indicated that ACOG does not have a preference about the vaccines. They 

felt that moving ahead with using the Janssen is appropriate in pregnant patients.
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

58

Dr. Drees (SHEA) agreed with others that the Janssen vaccine should be offered similar to the 

other two available vaccines to everyone who is eligible. HCWs have had access to the mRNA 

vaccine from the beginning, but many remain unvaccinated. Anyone who remains unvaccinated 

should have access to the Janssen vaccine as well. Some people may have a preference for a 

single dose, uncertainty about the mRNA technology, or other reasons why they might want the 

Janssen vaccine instead. It sends a good message that they are comfortable giving this vaccine 

to HCW and not just other eligible people.

Dr. Goldman (ACP) said that from the ACP perspective, he certainly thinks the ethical 

framework and allocation strategy that has been previously recommended is well thought out 

and favors maintaining the current strategy. They should look at all of the vaccines as 

somewhat interchangeable in the sense of getting the vaccine to as many people as possible. 

His concern with chronic conditions is that many jurisdictions are requiring physicians to certify 

patients’ health conditions, putting them in the precarious situation of making the patient have to 

disclose protected health information, patients not receiving vaccination who do not have 

access to healthcare, and/or the physicians having to certify heath conditions. He also 

expressed concern with preferentially going to certain jurisdictions and making it seem that this 

vaccine is being reserved for certain areas, minorities, and people of color. This may have the 

unintended consequence of making it seem like an inferior vaccine. It must be messaged 

correctly that this vaccine is effective, everyone should get it, it needs to go out to as many 

people as possible just as the other vaccines do, and it is important to respect minorities and 

people of color to make sure that the frontline gets it. This is why age-based strategies offer him 

great pause and concern in terms of ethics and equity.

Dr. Sanchez noted that based on what Janssen presented the previous day and in agreement 

with what ACOG said, from a neonatologist standpoint, he does not see any concerns about 

contraindications in pregnancy from a fetal standpoint to be vaccinated.

Dr. Howell (AIM) indicated that AIM surveyed its 64 awardees charged with allocating COVID1 vaccine and found that almost 60 are waiting for ACIP’s recommendations in terms of how 

to allocate the Janssen vaccine. AIM would appreciate any guidance that could be provided. It is 

likely that this vaccine will have to be allocated toward certain HCP in order to prevent providers 

from having multiple types of vaccine on hand, which could cause administration errors. It is 

likely that they would allocate toward public health or pharmacies in order for it to be allocated 

easier logistically and to prevent vaccine administration errors by having multiple vaccines on 

hand.

Dr. Poehling agreed with the first question that the Janssen COVID-19 vaccine is 93% 

protective against hospitalizations and deaths. It is known that there is far more demand than 

supply for vaccines. Giving jurisdictions flexibility makes sense to her. They also need to 

address the fact that there is a decrease in the lifespan among Black and Brown communities of 

1.9 and 2.7 respectively in the last year.

Dr. Romero said he thought the Janssen vaccine could be used widely across groups. ACIP is 

at a disadvantage in that initial reports on this vaccine focused on the differences of vaccine 

efficacy compared to the previous 2 vaccines. Messaging must go to all recipients that this 

vaccine is effective in prevention of hospitalizations and deaths. This is what he has been 

stressing to the constituents in his state.
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Vaccination Prioritization: What are the key challenges and opportunities of 

implementation guidance options for: 1) Additional age eligibility brackets <65 years; and 

2) Eligibility based on 2 or more high risk conditions.

Referring to the list of high-risk conditions that currently appear on the CDC website, Dr. 

Poehling expressed concern that the more frequent it is, the more likely it is going to show up. 

For example, thinking mechanistically, Type 1 and Type 2 diabetes are more similar than 

different and they both cause many problems. However, Type 1 diabetes is not on the list 

because it is less frequent. She suggested that perhaps they could adopt the influenza 

recommendations for high-risk conditions so that less common conditions are not excluded.

Dr. Romero indicated that individual states already are modifying the definition of diabetes to 

include Type 1.

Dr. Hayes (ACNM) asked whether there are any data on the variety of the guidelines from stateto-state in terms of how each state has made its own decisions about who are the priorities for 

the vaccines, and whether this might be useful moving forward.

Dr. Romero indicated that this information does exist from a number of sources, including CDC.

As a reminder, Dr. Dooling showed a schematic (Slide 31) of how prioritization was laid out 

when the ACIP voted on this matter in December 2020. Phase 1a included LTCF and HCP; 

Phase 1b included persons 75 and older and frontline essential workers; and Phase 1c included 

persons 65 to 74 years of age, other essential workers, and persons 60 to 64 years of age with 

high-risk medical conditions. She also showed the number of unique individuals estimated to be 

in each of those categories (Slide 32). A lot has happened since the time that the ACIP last 

voted. Many jurisdictions have adapted the guideline to their local needs and have moved to 

include all persons 65 and older earlier in their prioritizations, which has expanded Phase 1b.

Regarding vaccination prioritization, Dr. Lee said that she felt very challenged by ensuring that 

they continue to stress equity as a focus for implementation of the COVID Vaccination Program. 

Having information about age, race, and ethnicity in terms of severe disease, hospitalizations, 

and deaths would be incredibly helpful to know in terms of what the intended and unintended 

consequences might be. It also will be helpful to understand how comorbidities layer in. She 

worries about having additional age eligibility brackets, decrementing by 5 years at a time, 

because that functionally delays the ability to potentially effectively reduce deaths, particularly 

where there has been a disproportionate share of infection and severe disease in minority 

populations. She challenged them to think about implementation efforts in this space. Age alone 

does not tell the story clearly. The question about comorbidities has come up in terms of 

whether there are additional comorbidities in these age groups. The risk is not even across age 

groups. Someone who has multiple comorbidities and is 30 or 40 years of age might carry a 

different risk of mortality and hospitalization than somebody who is 50 years of age and 

perfectly healthy. She expressed her hope that they would continue to bring this back into view 

for those on the frontline who are trying to figure out how to best vaccinate given the resources 

they have.

Referring to Slides 40 and 41, Dr. Dooling highlighted data on deaths in 2020 that were 

associated with COVID-19. This basically tells them that for minority groups, a higher proportion 

of deaths occurred among younger age groups. For White, non-Hispanic groups as has come to 

be expected, as the older age groups take up a higher and higher proportion of the deaths 

among that particular race/ethnicity group. The opposite trend is occurring in other minority 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

60

groups, whereby the highest proportions of deaths are happening among people in their 30s, 

40s, and 50s.

Dr. Romero emphasized that he is not in favor of eligibility brackets under 65 years of age, 

which is being implemented in some states. While it is an easier way to distribute vaccine 

among large populations in the US, it will lead to inequity. Dr. Dooling presented data earlier 

that clearly showed this. In the rush to administer vaccine, equity cannot be sacrificed. That has 

been a primary principle of the ACIP in developing these guidelines and they need to stand by 

that. Dr. Lee agreed completely.

Dr. Poehling also agreed with Dr. omero’s statement and the rationale behind it for eligibility. 

She does think that the high-risk conditions are concerning. Dr. Goldman explained earlier that 

he is personally being asked to sign off on conditions. She encouraged ACIP to think about 

simplifying the high-risk conditions to something like those for influenza vaccine, because they 

seem to be very similar. She worries that saying 2 or more conditions will create administrative 

barriers.

Dr. Dooling called upon the SME who is working on the list of high-risk conditions, Dr. Naeemah

Logan to speak to future directions.

Dr. Logan responded that in attempting to answer this question, it may be helpful first to provide 

some context to clarify. The primary purpose of the list on the consumer webpage is and always 

was to inform individuals about risks, but the list is not exhaustive and does not include every 

condition that may increase one’s risk of getting COVID-19. This is clearly stated on the current 

webpage. They understand that ACIP provides a framework for decision-making regarding 

prioritization and realize the challenges everyone is facing. They hope that HCP and 

jurisdictions will consider additional conditions as consideration for vaccination.

Dr. Daley reminded everyone that he raised two issues about age bands on a COVID-19 

Vaccines Workgroup call, in part because he was asked by local public health who said they 

were struggling to figure out how to implement that at mass vaccination clinics. While he 

appreciates the challenges that local public health is facing with implementation, the solution is 

not to abandon the strategy that has been taken for exactly the reasons Dr. Romero outlined, 

given that it is more likely to increase inequality.

Dr. Long said she found this issue to be somewhat more difficult, not because of the principle 

but in thinking about how unnamable the current recommendations are. Some states and 

jurisdictions where HCP are currently giving vaccine to their patients who are much younger. 

She is also concerned that multigenerational families are not eligible thus far, most of which 

have younger people who are taking care of older individuals. Although this is being done 

because of principle and equity, the translation of guidance has resulted in inequity in some 

situations. Those who have good follow-up in healthcare systems who do not have underlying 

conditions may be getting vaccinated, while those who do not have a medical home, are less 

well-cared-for, or are less informed about ways to get on lists are not getting vaccinated. She 

expressed her hope that ACIP could clarify at least the risk conditions to make that manageable 

and that this recommendation does not stand for longer than 30 to 60 days.
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

61

Dr. Talbot noted that her other daytime job is collecting information on people who are 

hospitalized with COVID-19 and agreed that the most common conditions in the US are the 

ones that come up first and the rare ones do not. Simplifying the high-risk conditions as they 

did for influenza would have great impact. However, she would not use 2 or more high-risk 

conditions because there could be a well-controlled diabetic and well-controlled hypertensive 

who get in line before someone who has poorly controlled diabetes. She also did not think they 

should start trying to make hierarchies of whose disease is more severe than others. The impact 

of certain diseases compared to others is not known with regard to one’s risk for COVID-19. The 

goal is to vaccinate everyone with a high-risk condition and ultimately everyone in the US. They 

have to stress to people that they are working their way to getting everyone vaccinated and to 

please be patient. She also emphasized that they should not expect anyone to police this. There 

are going to be people who will try to cheat the system. It is not worth wasting time arguing

about that. She supported continuing with the recommendations as designed and simplify and 

be more inclusive for people with high-risk conditions.

Dr. Bell stressed that the ACIP wants to be as helpful as possible at any juncture to further the 

goals as Dr. Dooling laid them out. ACIP is providing guidance or advice to CDC. Dr.

Messonnier asked them earlier to tell CDC what ACIP thinks about the Janssen vaccine, for 

which they provided feedback. Now they were on the issue of the list and, as everyone could 

hear and as she has been hearing as the Chair of the WG for quite some time, there is a lot of 

anxiety and displeasure with this list. While she recognizes that they are at a certain juncture, 

she was hopeful that within a month they would not have to worry about this list. The list is 

currently a problem and barrier for many on the frontline in many states. Therefore, there is a 

need to address this list in some way. They heard from Logan at CDC that what they are doing

in terms of the list is not actually going to address the concerns raised by the committee. One 

could make the case that the reality is that ACIP has used this list and cannot rewrite history. 

She felt that it would be very difficult for the ACIP to do anything other than state what they think 

the objectives of improving the list should be. They heard that there are some concerns about 

complexity, so she expressed hope that CDC address these concerns that they were hearing 

loud and clear about current status of this list.

Dr. Sanchez agreed that it is a difficult decision to go to less than 65 years of age. He thinks 

using the age strata in terms of who receives the vaccine is the easiest route because at least 

there is something concrete upon which to decide. Among the states that have vaccinated those 

over 65 years of age, it is because that is where the majority of deaths are occurring. He 

understands the need for equity, but also understands high-risk conditions that put some 

individuals at higher risk are essential to consider. He also agreed that documentation would not 

be feasible. In addition, he agreed that they must start including contacts of individuals who are 

high-risk themselves, particularly the elderly. Those who care for elderly individuals or other 

compromised individuals at home should be prioritized.

Dr. Bernstein noted that based on the phased allocation, the number of unique persons in each 

group for Phases 1a, 1b, and 1c is 202 million. With 72 million doses already administered and 

240 additional anticipated within a month from the 3 manufacturers, he thought that broadening 

this to reach as many people as possible might be appropriate at this point in order to include 

those in different age groups and with high-risk conditions without documentation from any 

provider.
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Dr. Poehling add that 160 to 170 million doses were expected to be distributed by the end of 

March, so a lot more people should be able to be vaccinated. She also expressed concern 

about requiring 2 or more high-risk conditions, given the difficulty in trying to judge who that is 

and the potential to create health inequities. She wondered whether the MMWR update would 

offer an opportunity to provide an update on high-risk conditions as well.

Dr. Cohn clarified that the MMWR would discuss only the Janssen recommendation made the 

previous day, and that CDC was discussing a separate web-based implementation guidance 

document that is nimbler and can be updated frequently. This would address how to think 

through the list, which already was in the process of being updated as described earlier.

Dr. Lee agreed that they should not state 2 or more high-risk conditions, given that there is not 

enough information to compare high-risk conditions. While that information is needed, trying to 

implement based on that makes an assumption about the science and data that are simply not 

available. Among the proportion of people hospitalized in pediatric and young adult populations, 

the most common condition is obesity. That does not necessarily mean that they have other comorbid conditions. It is important to be inclusive in the ability to vaccinate the younger adult and 

older teen populations, particularly for younger populations who may not have multiple 

comorbidities. That also includes an example of pregnancy, which is a high-risk medical 

condition for which requiring 2 conditions makes no sense as that would exclude the majority of 

pregnant women. She strongly stated that she did not support moving toward 2 or more highrisk conditions for implementation. For the record, she said she thought that families of 

individuals who cannot get vaccinated but are at the highest risk should be prioritized above the 

general population, such as stem cell transplant patient. She emphasized that at this stage in 

the vaccination program, they must move away from a punitive approach to an improvement 

mindset in thinking about vaccine implementation. Many facilities are extremely worried about 

getting it exactly right, it is actually inhibiting access except for those who are the strongest 

advocates. The more restrictions they place on things, the more likely it will continue to 

inadvertently create a disincentive for enhanced outreach. Given that the intent is to vaccinate 

everyone anyway, other than in the most egregious of situations, access should be provided 

and states and jurisdictions should move toward a more positive mindset.

Dr. Hutchins (NMA) expressed gratitude for sharing the slide of the higher proportion of deaths 

among younger age groups among populations of color compared with non-Hispanic White 

populations. She asked whether CDC had a slide of current age-specific risk of severe COVID19 disease (hospitalization and death) by race and ethnicity? 

mRNA Vaccine Dosing: What additional data are needed to inform: 1) delay the second 

dose; and 2) a single dose of mRNA vaccine for individuals with confirmed prior SARSCoV-2 infection?

Dr. Sanchez asked whether the study showing reactogenicity after the first dose was for both 

the Pfizer and BioNTech nRNA vaccines.

Dr. Oliver indicated that the pre-print article refers to a single dose of mRNA and does not 

specify between the Pfizer and BioNTech nRNA vaccines. CDC does not have reason to think 

that there would be substantial difference between the two. 

Dr. Sanchez wondered about the current guidance in terms of the second vaccine dose to 6 

weeks only and where that comes in, given that it will have issues with respect to later doses.
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Dr. Dooling clarified that the current guidance is to adhere to the 3- to 4-week interval as closely 

as possible, but that a 6-week interval may be used for the purpose of scheduling in extenuating 

circumstances where that is not possible. The 42-day interval was used as the analytic interval 

in the Moderna and Pfizer analyses, with very few doses were given out that far.

Dr. Sanchez disagreed with delaying the second dose of the mRNA vaccine at this time and 

emphasized that they need to follow the science from the RCTs showing optimal efficacy in 

order to bring this pandemic under control. Eliminating and delaying a second dose at this time 

has the potential to raise questions about whether the vaccine is needed at all. Therefore, they 

should abide by the current recommendations and guidance that are supported by what the 

evidence has shown thus far. Whether a single dose is sufficient for those with confirmed prior 

infection is an intriguing and important question. Gathering additional information on this will be 

extremely beneficial, because it is possible that these individuals may not require a second dose 

if one infection turns out to develop an anamnestic response such that the vaccine would act as 

a booster dose.

Dr. Talbot did not feel the need for more data on the second question as they know there is a 

prime boost with the first dose, and the data they were shown are sufficient to make a decision 

rather than waiting on the second part of the question.

Ms. Bahta agreed with Dr. Sanchez said about the second dose. More information is needed, 

especially in light of variance development. For the second question, it made sense to her from 

a priming and boosting standpoint that only a single dose may be necessary. However, she 

would like to know more about the behavior of coronaviruses and how the vaccination might 

compare to the reoccurrence of diseases.

Dr. Lee agreed that there are not sufficient data to delay the second dose beyond what is 

currently recommended of up to 6 weeks. If there are large differences identified, they can be 

dynamic about their decision-making process. She also agreed with Dr. Talbot in part because 

she does feel that the infection is the prime and the vaccine is the boost. She did not see any 

advantage to giving a second dose either from an immunogenicity standpoint or from a safety 

standpoint. She feels like the second dose is not necessary and felt that she had sufficient 

evidence for that now.

Dr. Long agreed with everything stated thus far for all of the reasons presented. Delaying a 

second dose would be very confusing. Regarding the second question, she would like to see 

more data on harm or systemic reactions among people who previously had coronavirus 

disease and were then vaccinated in terms of whether they needed a second dose. Over time 

with more data, they may even learn that perhaps people who had coronavirus disease do not 

need a first dose. Her own brother who lives in Alaska where there was no coronavirus in March 

became severely ill, recovered fully, and had a central nervous system (CNS) vasculopathy 8 to 

9 months later for no explicable reason other than perhaps related to coronavirus and from 

which he recovered. He got his first vaccine and had a recrudescence of the CNS symptoms. 

Whether that was from coronavirus is unknown. It may have been from an inflammatory 

response. It is important to know whether the first dose confers enough benefit to be worth the 

risk of harm. For her, it seems that the second dose would have much more likelihood of harm 

than benefit that perhaps this should remain a relative contraindication until more is known.

Dr. Romero agreed with the theory and science already presented, but it is important to 

remember that the data available on the boosting after the first dose in individuals previously 

infected are in individuals who already have adequate or high titers of antibody to SARS-CoV-2. 

The question in his mind regards what happens to individuals with no antibody or very low 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

64

antibody at the time of being sampled. While he agreed that an anamnestic response is most 

likely to occur, it is not clear whether people have enough memory B cells available to boost to 

levels that would be protective. Those are the studies that he thinks will need to come forward.

Ms. Stinchfield (NAPNAP) agreed with Dr. Romero that they need to understand the longevity of 

protection. She has not been a fan of the recommendation to delay the second dose due to 

concerns about variants. Reflecting on the good science/ethics/implementation triangle, most 

scheduling systems are developed for the 2 doses and the first and second appointments are 

made at the same visit. To change that would be a significant lift on the ground.

Dr. Bernstein agreed that for the first question, they should go where the science leads them 

and should stay where they are at the moment. He also agreed with Dr. Romero and others 

regarding the second questions, given that more data are needed about correlates of protection, 

duration of immunity, and how the current mRNA vaccines fit with the variants that are 

increasing in the community. With that in mind, he was not enthusiastic about a single dose in 

those with confirmed prior SARS-CoV-2 infection.

Dr. Bell agreed with others on Question 2, including on making this a priority in terms of 

obtaining additional data. They certainly do not want to do harm. She was not comfortable 

making a recommendation because it makes immunologic sense. Insufficient information is 

known about the unintended consequence. There is also the issue about knowing who has 

antibodies and who does not and want happens with a single dose for those who do not have 

antibody. In terms of what ACIP can do, it would be very useful for the committee to send a 

strong message that this needs to be a priority for study. It may not be that difficult logistically to 

obtain this additional data in order to make evidence-based recommendations on this topic. The 

current recommendation about how long after SARS-CoV-2 infection a person should wait to 

get vaccinated is to consider waiting for 90 days. Her understanding anecdotally is that a lot of 

people rushed to get a vaccine after infection. She wondered whether people had an opinion 

about whether it would be useful to clarify or strengthen the guidance about waiting for a while 

after a confirmed infection even to get a single dose.

Dr. Sanchez emphasized that those who have had symptomatic disease very likely will have an 

immunologic response, which raised concerns for him about having the first dose. He also 

thinks guidance is needed in terms of the 6-week delay after the first dose, as well as those who 

are beyond the 6-week delay for the second dose.

Dr. Fink (FDA) supported the statements made by Drs. Romero, Bell, and others. They all want 

to make the best recommendations possible to cover the universe of potential circumstances. 

He acknowledged that the ACIP has the difficult task of developing recommendations to cover 

situations and circumstances not covered in the FDA labeling and even on occasion makes 

recommendations that are off-label for approved products when this makes sense and is 

backed by data. The fact is that at this time, these COVID-19 vaccines remain unapproved 

products that are available under EUA. The label used under EUA is based on data that are 

sufficient to support that use, but are rapidly evolving and that FDA continues to gather. He 

agreed that gathering more data to inform use in previously infected individuals and to inform 

potential changes to dosing intervals should be priority. At this time, they certainly do not have 

data to support any of the types of proposals being discussed in terms of the labeling of these 

unapproved products that are made available under EUA.
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Dr. Kotton said that she was comfortable with the immunologic data for Question 2 in terms of a 

single dose for confirmed infection. There may be a need for boosters in the future, which will be 

an interesting area for which they do not have significant information. Hopefully, more 

information will be available about correlates of protection that will help ACIP make good 

decisions. While a single dose of mRNA vaccine would be acceptable for healthy people who 

have had COVID-19 infection, but it probably would not be adequate for immunocompromised 

populations. It will be challenging to create a guideline that would fit everybody and would 

probably require distinguishing between different at-risk cohorts.

 eferring to Slide 2 in Dr. Dooling’s presentation, Ms. McNally noted that the third bullet under 

next steps said that any update would be made in collaboration with FDA. She wondered 

whether this involves a formal collaboration process or if these are ongoing discussions and 

how the public becomes aware the discussions. In terms of reactogenicity among persons with 

prior infection, she wondered how they would be made aware.

Dr. Dooling responded that there are numerous mechanisms for FDA and CDC collaboration, 

including informally as agencies within the HHS structure and additionally through the 

collaborations with ACIP, with Dr. Doran Fink being the ex officio member who represents FDA 

at the ACIP table and also sits on the COVID Workgroup of the ACIP to name a couple of 

mechanisms. Regarding reactogenicity, there are no current mechanisms to state that there is 

any difference in reactogenicity for persons who may have had prior infection.

Dr. Cohn added that CDC is currently assessing its data sources and ability to examine whether 

there is increased reactogenicity or AEs among people who previously have had infection, and 

should soon have an update for the ACIP.

Clinical Considerations for Use of COVID-19 Vaccines

Jessica MacNeil

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention

Ms. Mac eil reviewed CDC’s clinical considerations for the use of COVID-19 vaccines in the 

US. CDC’s clinical considerations for mRNA COVID-19 vaccines were presented to ACIP in 

December 2020 and are published on the CDC website. During this session, she presented 

proposed updates to the clinical considerations to include information on the newly authorized 

Janssen viral vector COVID-19 vaccine. In addition, she highlighted other key updates that have 

been raised as clinical considerations since the December 2020 ACIP meeting. These 

considerations will continue to be updated as additional information becomes available or if 

additional vaccine products are authorized. She also noted that people can sign up on the CDC 

website to receive email updates when the clinical considerations are updated.40

Beginning with vaccine administration, COVID-19 vaccines are administered intramuscularly as 

either a 2-dose series or as a single dose. One valid vaccination series should be administered, 

meaning either a 2-dose mRNA COVID-19 vaccine series or a single dose of Janssen COVID19 vaccine. Individuals are not recommended to receive more than one complete COVID-19 

vaccination series at this time. he vaccines’ authorized age groups, dose volumes, number of 

doses in the vaccine series, and the interval between doses are shown in this table which is 

also included in the clinical considerations document:

40 https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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Vaccine Dose Dose Volume Number 

Doses/Series

Interval 

Between Doses

Pfizer-BioNTech 30 μg 0.3 ml 2 3 weeks (21 days)

Moderna 100 μg 0.5 ml 2 1 month (28 days)

Janssen 5×1010 viral particles 0.5 ml 1 N/A

Any of the currently authorized COVID-19 vaccines can be used when indicated. The ACIP 

does not state a product preference. However, the COVID-19 vaccines are not interchangeable

and the safety and efficacy of a mixed product series has not been evaluated. In exceptional 

situations where the first dose of an mRNA COVID-19 vaccine was received but the patient is 

unable to complete series with either the same or different mRNA COVID-19 vaccine (e.g., 

contraindication), a single dose of Janssen COVID-19 vaccine may be administered at minimum 

interval of 28 days from the mRNA COVID-19 vaccine dose. However, these patients should be 

considered to have received a valid, single-dose Janssen vaccination, not a mixed mRNA/viral 

vector series. The currently authorized COVID-19 vaccines are all inactivated vaccines. COVID19 vaccine should be administered alone with a minimum interval of 14 days before or after 

administration with any of the other vaccines. However, a shorter interval may be used in certain 

situations where the benefits of vaccination are deemed to outweigh the potential unknown risks

of vaccine co-administration (e.g., tetanus toxoid vaccine for wound management, rabies 

vaccination for post-exposure prophylaxis, or measles or hepatitis A vaccination during an 

outbreak) or to avoid barriers or delays to COVID-19 vaccination (e.g., LTCF residents or HCP 

who received influenza or other vaccinations prior to admission or onboarding).

Regarding the considerations for vaccination among people with prior or current SARS-CoV-2 

infection, persons with prior SARS-CoV-2 infection should be offered vaccination regardless of 

history of prior symptomatic or asymptomatic SARS-CoV-2 infection. Data from clinical trials

suggest that the currently authorized COVID-19 vaccines can safely be administered to persons 

with evidence of a prior SARS-CoV2 infection. Viral testing for current infection or serologic 

testing for prior infection is not recommended for the purpose of vaccine decision-making. 

Vaccination among persons with known current SARS-CoV-2 infection should be deferred until

the person has recovered from acute illness if person had symptoms and criteria have been met 

to discontinue isolation. While there is no recommended minimal interval between infection and 

vaccination, current evidence suggests that reinfection is uncommon in the months after initial 

infection. While vaccine supply remains limited, persons with recent documented SARS-CoV-2

infection may choose to temporarily delay vaccination if desired, recognizing that the risk of 

reinfection and therefore the need for vaccination might increase with time following initial 

infection.

41

There are currently no data on the safety and efficacy of COVID-19 vaccines in persons who 

received monoclonal antibodies or convalescent plasma as part of COVID-19 treatment. Based 

on the estimated half-life of such therapies and evidence suggesting that reinfection is 

uncommon in the 90 days after initial infection, vaccination should be deferred for at least 90 

days. This is a precautionary measure until additional information becomes available to avoid

potential interference of the passive antibody therapy with vaccine-induced immune responses. 

This recommendation does not apply to persons receiving antibody therapies not specific to 

COVID-19 treatment. There is currently no recommended minimum interval between antibody 

therapies not specific to COVID-19 treatment and COVID-19 vaccination.42

41 https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-in-home-patients.html; https://www.cdc.gov/coronavirus/2019-

ncov/hcp/duration-isolation.html

42 https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html
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In terms of COVID-19 vaccinations in special populations, COVID-19 vaccines can be 

administered to persons with underlying medical conditions who have no contraindications to 

vaccination. The clinical considerations document includes information for vaccination of 

immunocompromised persons; those with autoimmune conditions; and people with a history of 

Guillain-Barré syndrome (GBS), Bell's palsy, and dermal filler use. Clinical trials have 

demonstrated similar safety and efficacy profiles in persons with underlying medical conditions, 

including those that place them at increased risk for severe COVID-19 compared to persons 

without comorbidities.

43

Persons with HIV infection, other immunocompromising conditions, or who take 

immunosuppressive medications or therapies might be at increased risk for severe COVID-19. 

Immunocompromised individuals may receive COVID-19 vaccine if they have no 

contraindications for vaccination, but should be counseled about the unknown vaccine safety 

profile and effectiveness in immunocompromised populations, as well as the potential for 

reduced immune responses and the need to continue to follow current guidance to protect 

themselves against COVID-19.44

Observational data have demonstrated that pregnant people with COVID-19 have an increased 

risk of severe illness, though the absolute risk is low. Additionally, they may be at increased risk 

for adverse pregnancy outcomes. There are currently limited data on the safety of COVID-19 

vaccines in pregnant people. No safety concerns were demonstrated in animal developmental 

and reproductive toxicity (DART) studies in any of the animals that received any of the 3 

authorized COVID-19 vaccines. In addition, the adenovirus vector platform used in the Janssen 

COVID-19 vaccines has been used for other vaccine development programs that included 

pregnant people vaccinated during any trimester, including a large-scale Ebola vaccination trial. 

No adverse pregnancy-related outcomes, including infant outcomes, were determined to be 

related to the vaccines in these trials. Based on current knowledge, experts believe that COVID19 vaccines are unlikely to pose a risk to the pregnant person or fetus, because the currently 

authorized COVID-19 vaccines are all inactivated vaccines. However, the potential risks of 

COVID-19 to the pregnant person and fetus are unknown because these vaccines have not 

been studied in pregnant people. Clinical trials to evaluate safety and efficacy of COVID-19 

vaccines in pregnant people are planned or underway. The vaccine manufacturers are following 

outcomes in people in clinical trials who became pregnant.45

Pregnant people may choose to receive a COVID-19 vaccine when eligible. A conversation 

between the patient and their clinical team may assist with the decision about the use of 

COVID-19 vaccine, though a conversation with a HCP is not required prior to vaccination. When 

making a decision, pregnant people and their HCP should consider the level of COVID-19

community transmission, the patient’s personal risk of contracting COVID-19, the risks of 

COVID-19 to the patient and the potential risks to the fetus, the efficacy and side effects of the

vaccine, and the limited data about use of the vaccine during pregnancy.

43 https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html

44 https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html; 

https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html#phrecs

45 https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/pregnancy-breastfeeding.html; 

https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/special-situations.html
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Recommendations for contraindications and precautions for COVID-19 vaccines are 

summarized in this table:

This table summarizes information related to the contraindications and precautions by vaccine 

type:

In closing, Ms. MacNeil posed the following discussion questions for ACIP consideration and 

discussion:

❑ Does ACIP agree with the proposed clinical considerations related to vaccination?

❑ Are there any sections of the clinical considerations that ACIP would like to discuss?

Discussion Points

Dr. Romero noted that current guidelines state that 14 days after receipt of the second dose of 

an mRNA vaccine, an individual who has been fully vaccinated does not have to enter into 

quarantine and wondered whether the same would apply to the Janssen vaccine product.

Ms. MacNeil indicated that the current version of the clinical consideration does include a public 

health recommendation for vaccinated people. It has been updated to state 2 weeks following 

receipt of 1-dose of Janssen vaccine. This section of the guidance likely will be updated in the 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

69

next week or so with additional recommendations pertaining to quarantine for vaccinated 

individuals.

Dr. Drees (SHEA) recalled that Ms. MacNeil indicated that someone who received the first dose 

of an mRNA but was unable to receive a second dose due to a contraindication could get a 

single dose of the Janssen vaccine, but that some of the ingredients are similar such as 

polysorbate or polyethylene glycol (PEG). She asked whether patients who had a possible 

allergic reaction to the first vaccine should be advised to get the Janssen vaccine to complete 

their series.

Ms. MacNeil clarified that the way the considerations are written currently, persons who had a 

contraindication or anaphylactic reaction with either mRNA or Janssen vaccine will be 

considered to have a precaution against vaccination with the other type of vaccine. If they are 

vaccinated, it should be done in a setting where any reactions could be managed and have a 

30-minute observation period. 

Dr. Drees observed that the risk of anaphylaxis for the Pfizer and Moderna vaccines is very low 

at 2 to 5 cases per million doses given, which is similar to other vaccines for which 15 minutes 

of monitoring is not required. As she recalled, the majority of cases were among people with a 

history of severe allergy of some type and she wondered if there had been any consideration for 

dropping the 15-minutute monitoring recommendation for people who do not have that allergy 

history.

Ms. MacNeil indicated that the usual recommendation for any vaccine is to monitor the recipient 

for 15 minutes following vaccination. In terms of the 30-minute window following vaccination for 

people who have had anaphylactic reactions, people are still feeling relatively conservative and 

that is why the 30-minute window was maintained. She is fine with the 30-minute window for 

high-risk people. From an implementation standpoint, there are large mass vaccination 

influenza clinics all of the time and the majority do not monitor for 15 minutes. Therefore, this 

feels very different from other vaccines.

Dr. Mbaeyi added that they have been thinking through this and conducting analyses of the 

anaphylaxis cases that have been reported so far in terms of trying to understand the 

incremental benefits of a 30-minute wait period for high-risk patients. They would like to review 

more data before making a decision.

Dr. Poehling emphasized that because anaphylaxis to the two mRNA is very rare, she was still 

struggling with where the information was coming from regarding 28 days later with the Janssen 

vaccine it is not needed.

Ms. MacNeil indicated that the 28-day interval came from the interval that is being used 

between mRNA doses if one product is unknown. This was carried forward for this 

recommendation as well.

Dr. Mbaeyi added that they wanted to provide an interval and for it to be an appropriate interval 

not only for reactogenicity considerations, but also to ensure a good boost if it is going to be 

given as a dose after a previous mRNA dose. The 28-day window seemed most reasonable 

because the interval for the authorized Pfizer mRNA vaccine is 21 days and Moderna mRNA 

vaccine is 28 days.
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Dr. Daley noted that he was staffing a large vaccination clinic a couple of weeks previously and 

was amazed at the number of true precautions that arose and the number of things that were

not precautions but were perceived as such. The individual risk balance was still strongly in 

favor of vaccination that day and these were individuals who may have had significantly 

increased risk of COVID disease. Waiting because of a precaution puts them at risk of COVID. 

Therefore, he wondered whether there is a place to clarify that the vast majority of cases with a 

precaution for vaccination should be vaccinated that day after a conversation with whomever is 

there and perhaps just be observed for longer. 

Ms. MacNeil indicated that they will review the language to ensure that it is clear.

Dr. Sanchez recalled that the previous day when he asked about concomitant vaccinations with 

the Janssen product, it was indicated that other vaccines should not be given for 1 to 2 months 

and he wondered whether that was part of the 28-day window as well. He is very much in favor 

of having a more lenient approach to other vaccinations with any of these 3 vaccines.

Ms. MacNeil pointed out that all of the studies handled this issue differently. In terms of 

concomitant administration with other vaccines, the guidance states that there should be 14 

days between the administration of COVID vaccine and any other vaccines unless there is an 

urgency to receive the vaccine such as tetanus for wound prophylaxis.

Dr. Cohn added that they are looking very closely at concomitant administration and the 14-day 

interval. They plan to review the safety data to evaluate whether there is an ability to relax that 

guidance in the near future.

Referring to Slide 9, Dr. Lee stressed that increasing younger population will begin to be 

vaccinated in the coming months. She worries about late complications of COVID-19 such as 

Multisystem Inflammatory Syndrome in Children (MIS-C) or Multisystem Inflammatory 

Syndrome in Adults (MIS-A). Even though there is a minimum interval between infection and 

vaccination other than the quarantine restrictions, she would say that advocating for waiting 4 to 

6 weeks makes sense from a clinical standpoint to ensure that they are not conflating late 

complications of COVID-19 infections versus AEs to the vaccine. Many considerations may be 

important in terms of the timing.

Ms. Stinchfield (NAPNAP) said she was glad that the professional societies are supporting

vaccination of pregnant women with all of the products available, but fever in a pregnant woman 

should be avoided for the fetus. She wondered if the Janssen product would be preferable for 

that reason, given that the risk of fever is reduced because of just one dose.

Dr. Meaney-Delman indicated that CDC did discuss this with their colleagues at ACOG and 

others and decided that they did not want to limit the opportunity for any vaccine. Whatever 

vaccine a pregnant woman has in front of her, she should receive. The guidance does include 

that acetaminophen can be given if temperature rises, which they think will address the issue.

Dr. Kotton found the considerations presented to be excellent overall, but highlighted a phrase 

in the middle of Slide 13 reading, “all currently authorized vaccines are inactivated vaccines.” 

She suggested considering a different word than “inactivated” in that this implies that they have 

been active and were rendered inactive. For clarity and uptake, the Janssen vaccine is a nonreplicating viral vector and mRNA vaccines were never active in any way.

Ms. MacNeil indicated that they would revisit this wording.
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VaST Introduction

Grace M. Lee, MD MPH

Chair, ACIP COVID-19 Vaccine Safety Technical Subgroup

Associate CMO, Stanford Chil ren’s eal 

Professor of Pediatrics, Stanford University School of Medicine

Dr. Lee provided an overview of the COVID-19 vaccine safety activities on behalf of the VaST

Subgroup. As a reminder, the objectives of the COVID-19 VaST Subgroup are to: 1) review, 

evaluate, and interpret post-authorization/approval COVID-19 vaccine safety data; 2) serve as 

the central hub for technical subject matter expertise from federal agencies conducting postauthorization/approval safety monitoring; 3) advise on analyses, interpretation, and data

presentation; and 4) provide updates to the ACIP COVID-19 Vaccines Work Group (WG)

and the ACIP on COVID-19 vaccine safety.

VaST has met 24 times since June 2020 and 10 times specifically since December 21, 2020 to 

review the post-approval vaccine safety data. The Janssen vaccine that was approved on 

February 28, 2021 has now been added. As a reminder, this graphic illustrates the vaccine 

safety surveillance systems engaged in the VaST meetings and as mentioned in prior ACIP 

meetings, vaccine safety monitoring has relied on v-safeSM, the VA Adverse Drug Event 

Reporting System (VA ADERS), the Vaccine Adverse Event Reporting System (VAERS), and 

Clinical Immunization Safety Assessment (CISA) early in the US vaccination program as early 

detection systems for safety: 

Dr. Lee expressed gratitude to federal colleagues and their investigator teams who have been 

collecting and reviewing these data each week for presentation to the VaST Subgroup. It takes 

a tremendous amount of effort each week for the teams to do this work and it requires them to 

be nimble, patient, and responsive to the VaS Subgroup’s many questions.

In terms of the VaS Subgroup’s procedures, the group engages in a weekly review of available 

data on vaccine administration and adverse events of special interest (AESI). All members, 

federal partners, and SMEs are present for presentation of data. VaST members discuss these 

findings independently after the meetings. A summary and interpretation of aggregate data are 

 

 

 

 

 

 
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provided to the ACIP Secretariat on a regular basis. Since the last ACIP meeting, VaST has 

covered the following topics:

❑ Reviewed routine data from VAERS, v-safeSM, VA ADERS, VSD, and CMS

❑ Reviewed special topics including:

– Background rates for AESI 

– Maternal immunization

– Thrombocytopenia

– Multisystem Inflammatory Syndrome (MIS)

– Vaccination of persons with prior infection 

❑ Initiated monthly sessions with additional experts to review data on vaccine safety in 

pregnancy 

This session included a COVID-19 vaccine safety update overall and with a special focus on 

maternal immunization at the request of ACIP members during the last meeting, as well as the 

COVID-19 VaST Subgroup’s discussion and interpretation of those data.

COVID-19 Vaccine Safety Update

Tom Shimabukuro, MD, MPH, MBA

Immunization Safety Office

Vaccine Safety Team

CDC COVID-19 Vaccine Planning Unit (VPU)

National Center for Emerging and Zoonotic Infectious Diseases

Centers for Disease Control and Prevention

Dr. Shimabukuro provided an update on v-safeSM, VAERS, VSD, CISA, and COVID-19 vaccine 

safety in pregnancy. As a reminder, v-safeSM is CDC’s smartphone-based active surveillance 

system that uses text messaging with links to web-based surveys to help conduct check-ins on 

individuals after vaccinations. These check-ins occur daily the first week after vaccination, 

weekly through 6 weeks, and then at 3, 6, and 12 months. This process basically resets when a 

person has a second dose. The daily check-ins during the first week post-vaccination solicit 

responses on local and systemic reactions. Local and systemic reactions are not asked about 

after that. On all check-ins, there is a health impact assessment. If an individual reports that 

they received medical care, that information is transmitted to a VAERS call center, the person is 

contacted, and a VAERS report is taken if appropriate. There are also questions on the surveys 

to capture information on pregnancy status. An effort is made to enroll people who were 

pregnant at the time of vaccination or became pregnant after vaccination in the v-safeSM

pregnancy registry through a separate process.

Based on an analysis of v-safeSM data as of February 16, 2021, approximately 55 million people 

had received 1 or more doses of COVID vaccine in the US and roughly 3.9 million v-safeSM

registrants had completed at least 1 health check-in. Of these, there were just over 30,000 selfreported pregnancies in v-safeSM. It is known from reviewing the data that the highest amount of 

reactogenicity is reported on Day 1. Based on a fairly recent publication in the MMWR on the 

initial safety findings for mRNA COVID-19 vaccines, comparing Dose 1/Day 1 (the day after 

vaccination) of the Pfizer-BioNTech and Moderna vaccines, the safety profiles are quite similar 

and consistent. The takeaway is that a substantial amount of reactogenicity is reported and 

these vaccines are known to be reactogenic. In terms of Day1/Dose 1 compared to Day 1/Dose 

2 of the Pfizer-BioNTech vaccine, striking is that the reported systemic reactions are 

substantially more following Dose 2. In some cases, they are 3- to 4-fold higher. Therefore, the 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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reactogenicity profiles based on v-safeSM are consistent with what was observed in the clinical 

trials in terms of reactogenicity in general and the observation that there is more systemic 

reactogenicity after Dose 2. At the time of this analysis, CDC did not have information on Dose 

2 of the Moderna vaccine. They now have those data and will be updating this analysis in the 

future.46

VAE S is the nation’s early warning system for vaccine safety. It is a spontaneous reporting or 

passive surveillance system that is co-managed by CDC and FDA. The strengths of VAERS are 

that it is national data of essentially the entire US population who is eligible to receive a vaccine. 

Because of the size and breadth of VAERS, it can rapidly detect safety signals and rare AEs. 

The main limitation is that VAERS is not designed to assess causality. VAERS accepts all 

reports from everyone regardless of the plausibility of the vaccine causing the event or the 

clinical seriousness of the event. As a hypothesis-generating system, VAERS identifies potential 

vaccine safety concerns that can be studied in more robust data systems. As of February 16, 

2021, there were just over 104,000 reports to VAERS of which 94% are non-serious and 6% are 

serious. That breakdown of serious and non-serious is similar to what is observed for other 

vaccines administered to adults such as influenza vaccines. Comparing the most commonly

reported AEs to VAERS after COVID-19 vaccines, systemic reactions are most commonly 

reported and local reactions are commonly reported for both the Pfizer-BioNTech and Moderna 

vaccines. The safety profiles for these two vaccines look remarkably similar. Importantly, no 

empirical Bayesian data mining alerts were detected for any adverse event-COVID-19 vaccine 

pairs. The takeaway message from the v-safeSM and VAERS data is that the initial safety 

profiles of these vaccines are consistent with what was observed in the clinical trials and are 

generally reassuring. In terms of anaphylaxis follow mRNA COVID-19 vaccines from a fairly 

recent publication in the Journal of the American Medical Association (JAMA)

47, after additional 

data were accumulated from the last time ACIP was briefed, there are updated reporting rates. 

For the Pfizer-BioNTech it is 4.7 cases per million doses administered and for Moderna it is 2.5 

cases per million doses administered.

The VSD is a CDC collaboration with 9 participating integrated healthcare organizations

data on over 12 million persons per year. The VSD has electronic health record data and 

administrative data to include information on immunizations, encounters with the healthcare 

system, birth and death certificate information, and demographics that are all linked by unique 

study identifications (IDs). The VSD also has rapid access to charts and electronic health 

records to go in and review cases. The VSD is conducting near real-time sequential monitoring 

called Rapid Cycle Analysis (RCA) for COVID-19 vaccines. In RCA, the data are refreshed 

weekly. The outcomes that are monitored are pre-specified (i.e., identified in advance). It 

includes methods to adjust for sequential testing when sequential testing is performed. RCA is a 

surveillance activity, which is not the same as an epidemiologic study. It is designed to detect 

statistically significant associations and statistical signals, which are values above specified 

statistical thresholds. Not all statistical signals indicate a safety problem and need to be 

assessed further. When a statistically significant association or signal occurs, assessment 

involves a series of checks and evaluations. Chart-confirmation of a diagnoses to confirm or 

exclude cases as true incident cases is a key part of statistical signal assessment.

46 Gee J, Marquez P, Su J, et al. First Month of COVID-19 Vaccine Safety Monitoring — United States, December 14, 2020–

January 13, 2021. MMWR Morb Mortal Wkly Rep. ePub: 19 February 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7008e3

47 Shimabukuro TT, Cole M, Su JR. Reports of Anaphylaxis After Receipt of mRNA COVID-19 Vaccines in the US—December 14, 

2020-January 18, 2021. JAMA. 2021;325(11):1101–1102. doi:10.1001/jama.2021.1967 
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The VSD RCA planned for COVID-19 vaccines include unvaccinated concurrent comparators 

(currently being conducted), vaccinated concurrent comparators (currently being conducted), 

self-controlled risk interval (planned), and historical comparators (planned). The combined total 

of VSD COVID-19 vaccine doses administered by February 12, 2021 was roughly 630,000 

Dose 1 doses and just over 200,000 Dose 2 doses. These doses are broken down by 

manufacturer, age group, and dose number through February 13, 2021 in the following table, 

with the blue bar (ages 65-84) having increased as time has gone on, likely indicating expansion 

of the vaccination program more toward the general population:

The VSD unvaccinated concurrent comparator analysis for COVID-19 vaccine safety after either 

dose of any mRNA vaccine through February 13, 2021 allowed CDC to get data most quickly on 

the following 21 pre-specified outcomes that are being monitored:

❑ Acute disseminated encephalomyelitis

❑ Acute myocardial infarction

❑ Acute respiratory distress syndrome

❑ Anaphylaxis 

❑ Appendicitis

❑ Bell’s palsy

❑ Convulsions/seizures

❑ Disseminated intravascular coagulation

❑ Encephalitis/myelitis/encephalomyelitis

❑ Guillain-Barré syndrome

❑ Thrombotic thrombocytopenic purpura

❑ Immune thrombocytopenia

❑ Kawasaki disease

❑ MIS-C and MIS-A

❑ Myocarditis/pericarditis 

❑ Narcolepsy and cataplexy

❑ Stroke, hemorrhagic

❑ Stroke, ischemic

❑ Transverse myelitis

❑ Venous thromboembolism

❑ Pulmonary embolism (subset of VTE)

 

 

 

 

 

 

 

 
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The concurrent comparator analysis is basically an assessment of vaccinated individuals 

compared to unvaccinated individuals matched on certain characteristics. It does not require 

maturation of vaccinated individuals into the control window, so it can provide information as 

soon as individuals begin to get vaccinated and events begin to accrue. No statistically 

significant increased risks were detected in this analysis for any of the prespecified outcomes in 

the unvaccinated concurrent comparator analysis. No statistical signals were detected in the 

preliminary results of the VSD sequential vaccinated concurrent comparator analysis for 

COVID-19 vaccine safety after either dose of any mRNA vaccine as of February 13, 2021. The 

next steps for the VSD RCA include dose-specific analyses, product-specific analyses, analyses 

for two risk intervals (1-21 and 1-42 days), and a historical comparator analysis.

The CISA project is a collaboration between CDC and 7 participating medical research centers. 

The CISA project, COVID-vax, is and e tension of CDC’s CISA48 Project’s clinical consultation 

service for US healthcare providers and health departments for complex COVID-19 vaccine 

safety questions/issues that are49 about individual patients residing in the US that are not readily 

addressed by CDC or ACIP guidelines50. The CISA team and its partners include individuals 

with vaccine safety subject matter expertise in multiple specialties (e.g., infectious diseases, 

allergy/immunology, neurology, OB/GYN, pediatrics, geriatrics). Requests for a CISA consult 

about COVID-19 vaccine safety can be made by contacting CDC-INFO: 800-CDC-INFO (800-

232-4636) or webform51 and indicating the request is for a “CDC CISA” consult (no patient 

identifiers).

CISA has responded to 331 clinical inquiries or consultation requests about COVID-19 vaccine 

safety during the period from December 14, 2020 through February 10, 2021. These requests 

were received from 43 states, with over 90% from healthcare provider or health departments. 

The most common topics include anaphylaxis/allergic reactions and nervous system disorders. 

This includes inquiries about AEs and for clinical guidance without AEs. The CISA project also 

has assisted state health departments with evaluation of complex medical issues pertaining to 

COVID-19 vaccine safety. The CISA Project also established a WG with allergy and 

immunology specialists to provide expert input on anaphylaxis and other allergic reactions to 

inform clinical considerations for use of COVID-19 vaccines. The WG is engaged in ongoing 

work to investigate a possible mechanism for anaphylaxis after COVID-19 vaccine in 

collaboration with FDA, NIH, and other partners.

Moving into COVID-19 vaccine safety in pregnancy, there have been just over 30,000 selfreported pregnancies reported during v-safeSM health check-ins as of February 16, 2021 as 

noted earlier. Looking at local reactions for Doses 1 and 2 post-vaccination for Pfizer-BioNTech 

recipients and Dose 1 for Moderna recipients, no substantial differences have been observed in 

local reactions in pregnant and non-pregnant women 16-54 years of age. In fact, there appear 

to be less reported reactions in pregnant women compared to non-pregnant women, although

the numbers are small. The same is observed with systemic reactions in pregnant compared to 

non-pregnant women. In fact, there may be more self-reported systemic symptoms in nonpregnant women. Substantially more systemic symptoms were reported after Dose 2 compared 

48 https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/cisa/index.html

49 Advice from CDC and CISA is meant to assist in decision-making, rather than provide direct patient management 

50 https://www.cdc.gov/vaccines/acip/recommendations.html

51 https://wwwn.cdc.gov/dcs/ContactUs/Form
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to Dose 1 for the Pfizer BioNTech vaccine, but there were no concerning patterns that differed 

among pregnant versus non-pregnant women.52

In terms of the v-safeSM pregnancy registry, participants who report pregnancy following COVID19 vaccination are actively contacted to enroll in the pregnancy registry. Participants are

contacted once per trimester, after delivery, and when the infant is 3 months old. The outcomes 

of interest include miscarriage and still birth, pregnancy complications, maternal ICU admission, 

adverse birth outcomes, neonatal death, infant hospitalizations, and birth defects. As of 

February 19, 2021, there were 1815 pregnant women have been enrolled in the v-safeSM

pregnancy registry. In the enrolled population, there have been 275 completed pregnancies, 

including 232 live births. Other outcomes have included miscarriage, stillbirth, ectopic/tubal

pregnancies, and other. In terms of v-safeSM pregnancy registry outcomes of interest in COVID19 vaccinated pregnant women as of February 18, 2021 compared to background rates based 

on the published literature, no concerning patterns have been observed.

Regarding characteristics of COVID-19 vaccine pregnancy reports to VAERS through February 

16, 2021, of which there have been 154, the median maternal age is 33 years (16–51) and the 

median gestational age is 13 weeks (2–38). Just over half of the reports involved pregnancies 

during the first trimester (60/118; 51%) , about a third during the second trimester (36/118; 

31%), and the remainder were in the third trimester (22/118; 19%). The vaccines received 

included 97 (63%) Pfizer-BioNTech, 56 (36%) Moderna, and 1 (0.6%) unreported. About 73% of 

the 154 reports involved non-pregnancy-specific AEs that would be expected in the general 

population that typically are systemic and local reactions as shown in this table:

Adverse Events N (%)

Pregnancy/Neonatal Specific Conditions 42 (27)

 Spontaneous abortion/miscarriage† 29

 Premature rupture of membranes 3

 Fetal hydrops 2

 Neonatal death in 22-week preterm birth 1

 Premature delivery 1

 Gestational diabetes 1

 Vaginal bleeding 1

 Stillbirth 1

 Shortened cervix 1

 Leakage amniotic fluid 1

 Calcified placenta 1

Non-Pregnancy Specific Adverse Events (top 10)

Headache (31), fatigue (29), chills (21), pain in extremity (17), nausea (15), dizziness (14), 

pain (14), pyrexia (13), injection site pain (13), injection site erythema (10)

112 (73)

To put the 29 reports of miscarriage into perspective, the frequency of clinically recognized early 

pregnancy loss for women 20 to 30 years of age is estimated to be between 9% to 17%, at age 

30 it is 20%, at age 40 it is 40%, and at age 45 it is 80%.53

There are other ongoing CDC COVID-19 maternal vaccination safety activities. In the VSD, 

there is a COVID-19 vaccination coverage project in pregnant women; a study on the risk of 

miscarriage and stillbirth following COVID-19 vaccination; and a safety in pregnancy study 

focused on acute AEs in pregnancy, longer-term safety assessment of acute AEs, pregnancy 

complications and birth outcomes, and infant follow-up for the first year of life. In the CISA

52 CDC unpublished v-safe data through January 13, 2021

53 ACOG Practice Bulletin No. 200: Early Pregnancy Loss. Obstet Gynecol. 2018132(5): e197-e207
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Project, a prospective observational cohort study is planned to examine adverse pregnancy and 

birth outcomes, SAEs, local and systemic reactogenicity, and infant health outcomes for the first 

3 months of life.

To summarize maternal vaccination safety, pregnant women were not specifically included in 

pre-authorization clinical trials of COVID-19 vaccines. Post-authorization safety monitoring and 

research are the primary ways to obtain safety data on COVID-19 vaccination during 

pregnancy. Substantial numbers of self-reported pregnant persons (>30,000) have registered in 

v-safeSM. The reactogenicity profile and AEs observed among pregnant women in v-safeSM did 

not indicate any safety problems. Most (73%) reports to VAERS among pregnant women 

involved non-pregnancy-specific AEs (e.g., local and systemic reactions). Miscarriage was the 

most frequently reported pregnancy-specific AE to VAERS. The numbers are within the known 

background rates based on presumed COVID-19 vaccine doses administered to pregnant 

women.

Closing thoughts on COVID-19 vaccine safety are that 75 million COVID-19 vaccine doses have 

been administered in the US through February 28, 2021. Reactogenicity profiles of mRNA 

vaccines in v-safeSM monitoring are consistent with what was observed in clinical trials, and 

systemic and local reactions are most commonly reported to VAERS. Anaphylaxis following 

both vaccines has been reported to VAERS, though rarely. No other safety signals for SAEs 

have been detected in VAERS. No safety concerns have been identified among VSD RCA

prespecified outcomes as of February 13, 2021. No unexpected pregnancy or infant outcomes 

have been observed related to COVID-19 vaccination during pregnancy. Safety monitoring in 

pregnant women is ongoing and planned in v-safeSM, VAERS, VSD, and CISA.

VaST Assessment of the Safety Data

Grace M. Lee, MD MPH

Chair, ACIP COVID-19 Vaccine Safety Technical Subgroup

 ss ia e O S an r il ren’s eal 

Professor of Pediatrics, Stanford University School of Medicine

Dr. Lee provided VaST’s discussion and interpretation of the safety data. Well-established 

vaccine safety surveillance systems remain the cornerstone for monitoring the safety of 

approved COVID-19 vaccines in the US. Enhanced approaches to surveillance have enriched 

the understanding of COVID-19 vaccine safety in the early phases of vaccine deployment. 

VaST continues to meet weekly to review all available data and to ensure a coordinated 

approach across multiple safety surveillance systems.

Local and systemic reactions continue to be the most commonly reported AEs following 

vaccination in v-safeSM, VAERS, and VA-ADERS. Anaphylaxis reporting rates range from 2.5 to 

4.7 cases per million doses administered and is the most common reason for CISA 

consultations. Allergy and immunology specialists provide expert input on clinical 

considerations. The VSD RCA uses multiple methods for surveillance depending on the phase 

of the vaccination program. Dr. Lee anticipates that into the future, VaST will continue to dive 

deeper into those VSD data. Pre-specified outcomes are actively being monitored and no

statistical signals have been detected to date. VaST also has reviewed the CMS RCA

descriptive analyses and the sequential analyses are to begin soon.
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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A large number of pregnant women have chosen to receive COVID-19 vaccines in the US. A 

novel pregnancy registry was established in v-safeSM to monitor pregnancy and birth outcomes.

VaST is greatly appreciative of CDC being nimble enough to establish such a registry. It was not 

anticipated that so many pregnant women would be interested in vaccination, so this is a great 

opportunity to have a better understanding of the safety and outcomes. Similar to non-pregnant 

adults, pregnant women commonly report local and systemic reactogenicity (e.g. pain, fatigue, 

headache). Pregnancy and birth outcomes following COVID-19 vaccination appear to be similar 

to rates reported in the literature.

Since the last ACIP emergency meeting at the end of January 2021, colleagues have published 

two additional vaccine safety publications in the MMWR and JAMA as Dr. Shimabukuro 

presented. CDC54 and FDA55 have each posted additional information on their web pages, with 

the anticipation that these will continue to be updated in the future.

In terms of VaST plans for the future, statistical signals should be expected in a robust 

monitoring program. Timely investigations will be conducted once signals are identified. Only 1 

in 10 statistical signals have been true associations. Maternal vaccine safety data from multiple 

sources will be regularly reviewed in collaboration with pregnancy experts. Future vaccine 

safety surveillance activities will include the newly approved Janssen COVID-19 vaccine. VaST 

will continue to update the ACIP COVID-19 Vaccines WG, the ACIP Secretariat, and the full 

ACIP on a regular basis.

Discussion Points (Lee & Shimabukuro)

Dr. Hahn (CSTE) recalled that v-safeSM also includes questions about whether any AEs have 

impacted activity in any way and wondered whether there are any data on this. Some people 

will not get a second dose if they have a severe allergic reaction to their first dose, but she 

wondered whether there have been any reports of severe allergic reaction among people with 

no reaction to the first dose who have an anaphylactic reaction to the second dose.

Dr. Shimabukuro indicated that part of the v-safeSM process is that if a person reports that they 

received medical care in any health check-in, there is an attempt to contact that person to take a 

VAERS report. CDC is in the process of collecting that information and analyzing those reports, 

and will report the findings of the v-safeSM-generated VAERS reports during a future ACIP 

meeting. There are some automated data in which people self-report that they have missed 

work or cannot engage in daily activities. He will take this back to the v-safeSM group to find out 

what type of analysis can be done with the data they have within v-safeSM in terms of using that 

as a proxy measure for severity. In terms of anaphylaxis with the second dose, most of the 

cases occur after the first dose based on the most recent published data and only a handful 

occur after the second dose. These data are from early in the vaccine rollout, so this may just 

represent the status of the rollout. Anaphylaxis continues to be monitored, but there still are not 

a lot of cases following the second dose. There could be a variety of reasons for that, which will 

require a deeper look. The pattern continues with most anaphylaxis reports occurring after the 

first dose and a relatively small number following the second dose.

54 https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety.html

55 https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/covid-19-vaccine-safety-surveillance
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Dr. Bernstein emphasized what an amazing job CDC is doing in monitoring the safety of the 

COVID-19 vaccines. eferring to slide 11 from Dr. Shimabukuro’s presentation, he observed 

that about 6% SAEs occurred, but it appeared that there was a lower number of doses in Pfizer 

than Moderna and more than twice as many SAEs after the Pfizer vaccine. He wondered 

whether that was because the data include more second doses. In addition, he asked whether 

Dr. Shimabukuro could comment on lymphadenopathy.

Dr. Shimabukuro stressed that these are spontaneous reports. The difference between 97% 

and 3% and 91% and 9% when dealing with spontaneous reports is difficult to determine. The 

two vaccines look fairly comparable in terms of the most common AEs. It is not clear whether in 

VAERS it will be possible to ascertain the true or meaningful difference, if any. Looking at the 

general pattern, about 90% non-serious and 10% serious is fairly standard depending upon the 

vaccine and the age of the individual being vaccinated. That is pretty standard for a lot of 

vaccines given for adults. Lymphadenopathy is not included as a pre-specified AE in the VSD 

RCA. There may be a variety of reasons for that, one of which regards whether it is medically 

attended. Typically for the VSD RCA, medically attended events are more conducive to 

monitoring. Lymphadenopathy and lymphadenitis reports have been received in VAERS and 

this was observed in the prelicensure clinical trials. These tend to be mild, non-serious, selflimited, and resolve pretty quickly on their own. No disproportional reporting has been observed 

for lymphadenopathy, nor has there been a safety signal for it. Lymphadenopathy occurs with 

other vaccines as well.

Dr. Lee reiterated that because VAERS is numerator only, VaST felt that it was hard to interpret 

the data due to the greater number of Pfizer doses given overall in the US at that time. There 

are differences in reporting behaviors. These reports are from people who actually report in. 

There was a lot of reporting in early on, which is terrific and encouraged, but there are changes 

over time and there could be changes in the numbers that do not actually translate into 

differences in AEs.

Dr. Bernstein said he was thinking that the 3-week interval for Pfizer products might be why 

there may me more second doses included, which tends to be more reactogenic.

Dr. Ault expressed gratitude for collection of all of the pregnancy data. He recalled that it was 

not that long ago that they were talking about the 300,000 HCP among the 20 million HCP and 

how that demographic skewed younger and female. These data should be very reassuring to 

the people who already have been vaccinated.

Dr. Poehling thanked Dr. Shimabukuro and his team for following the safety of these vaccines in 

real-time, which is incredibly important and demonstrates great confidence in this enormous 

effort. Referring to slide 21, she observed that the data on thromboembolism and pulmonary 

embolism appeared to be higher than the expected rates and requested additional information 

on this.

Dr. Shimabukuro indicated that it is still early and that follow-up time can impact the expected 

events. Their statisticians have indicated that the reason a small number like zero is expected 

sometimes is because some of the rare events have not accumulated follow-up time. In the 

unvaccinated concurrent comparator analysis does not rely on unvaccinated individuals moving 

through their follow-up time so certain vaccinated individuals can be compared with other 

vaccinated individuals. In this case, there are vaccinated versus unvaccinated so time can be 

accumulated right away. While there are limitations to this unvaccinated concurrent comparator 

analysis, in the early stages this was a way to obtain data as quickly as possible to get an idea 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

80

of what was occurring with associations and determine whether there was any statistically 

significant increased risks. They are in the process of transitioning into the VSD sequential 

vaccinated concurrent comparator, but need to accumulate more data and let more vaccinated 

individuals accumulate follow-up time. That will impact some of these numbers within expected 

events. Sequential statistical analyses are being performed on these. According to the 

thresholds, no statistical signals have been observed for any of these outcomes.

Ms. Bahta asked whether anything further could be said about nervous system disorders.

Dr. Shimabukuro indicated that these are primarily serious neurologic AEs such as GBS and 

other acute demyelinating disorders. It is important to remember that just because there are 

temporally associated cases of serious neurologic events does not imply that there is causal 

association or a safety problem. These are cases in which there is a temporally associated

event and an astute HCP or public health partner is requesting consultation, in which case CISA 

will do a deep review of these cases.

Ms. Stinchfield (NAPNAP) emphasized how useful these data are. She has 80 of Children’s 

Hospital of Minnesota staff vaccinated, but 10% have neither opted in or opted out. They are the 

people who are waiting and watching. She thinks these data will be extremely helpful to them in 

terms of safety. Regarding an earlier conversation, she wondered if consideration had been 

given to adding a question to v-safeSM such as, “Have you had a laboratory-confirmed case of 

COVID?” his might be a good time to do it with the addition of a third product.

Dr. Shimabukuro indicated that they do ask about COVID disease after vaccination. In some 

cases, that may be breakthrough disease and in others it may not depending upon the timing of 

the vaccination. They have had some long discussions and he could not recall why they opted 

not to include this. To get at the issue of reactogenicity and people who have been previously 

infected with COVID, a nested case-control study in v-safeSM is in the planning stages in which 

reactogenicity will be assessed in recipients, cases and controls will be selected, and then 

contact will be made with these individuals to ask about prior infection. There is a lot of interest 

in the issue of reactogenicity and whether prior symptomatic infection may predispose an 

individual to having more reactogenicity. They thought this would be the best way to analyze 

these data in v-safeSM.

Dr. Arthur (BIO) thought inclusion of the background rates was beneficial in helping people 

understand these data and make sure that the explanation of these incidents within the 

vaccinated groups are explained well to the general public. Referring to slide 8, Dr. Arthur said 

she has been hearing anecdotally that there is much more reactogenicity in younger people. 

Perhaps it would be good to see how the Dose 2 data split out by age groups and to 

communicate to people what to expect.

Dr. Shimabukuro indicated that they have a study underway that is assessing reactogenicity, 

which is much more detailed than what is presented on the two tables on slides 7 and 8. The 

investigators may already be doing this, but he will present Dr. Arthur’s suggestion to them in 

case they are not.

Dr. Hayes (ACNM) reiterated that the background rates are critical in terms of AEs and 

pregnancy. She reported that she volunteered at two clinics where most of the people did not 

know about v-safeSM, so she feels like the promotion of this is still missing on some level. She 

has 10 friends who were vaccinated, none of whom were told about v-safeSM. Noting that there 

has been some concern about women getting a mammogram immediately after being 
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81

vaccinated because of the lymphadenopathy and having a false positive mammogram, she 

asked what CDC has heard about this and if they are monitoring it. In addition, she inquired as 

to whether there has been a way to track whether reactogenicity is related to body mass index 

(BMI).

Dr. Shimabukuro acknowledged that the acceptability of v-safeSM has been somewhat 

inconsistent, so CDC certainly will speak to the communications team to maintain awareness of 

v-safeSM as vaccination rolls out more broadly. He is aware of the issue of lymphadenopathy

and mammograms, which would lie more within the purview of the group that issues clinical 

recommendations. Lymphadenopathy and lymphadenitis has been observed in postauthorization safety monitoring. BMI is not one of the variables used in the surveillance, so he 

could not comment on that or whether it is biologically plausible.

Dr. Long emphasized how remarkable it is to have so much data already. Regarding the 

background occurrence rate specifically related to pregnancy outcomes, it is known that there is 

overrepresentation in AEs of pregnancy in very young pregnant women in racially differentiation 

as well as socioeconomics. She assumed that background pregnancies from the medical 

literature outcomes includes everybody and that there was no attempt to try to match outcomes 

by age, race, socioeconomic status (SES), et cetera. She presumed that vaccinated pregnant 

women are more likely to be white, educated, and SES advantage. The stillbirth rate was 1% for 

vaccinees and 0.5% from the medical literature. She wondered whether there were any 

concerns about mismatching of the groups being assessed.

Dr. Shimabukuro said that part of enrolling women into the v-safeSM pregnancy registry is to 

conduct detailed intake interviews, so they are likely to obtain demographic information. When 

the v-safeSM pregnancy registry begins to form up and has larger numbers and more detailed 

information, it may be possible to perform some subgroup analyses. While the numbers are still 

fairly small and there are not sufficient data to allow for detailed sub-analyses at this point, that 

is a possibility as they continue to develop the v-safeSM pregnancy registry.

Dr. Sanchez thought it would be helpful with the nested case-control study to ask who had a 

SARS-CoV-2 infection before being vaccinated. In terms of pregnancy, it would be interesting 

as new platforms are developed to assess the safety and AEs including overall side effects by 

vaccine type.

Dr. Duchin (NACHO) asked for which systems race and ethnicity data are available, and if there 

are sufficient data to stratify analyses by race and ethnicity. In addition, he wondered about 

participation rates.

Dr. Shimabukuro indicated that race and ethnicity data are captured on the standard VAERS 2.0 

reporting form. Race and ethnicity have been added to the v-safeSM system. It is asked at initial 

intake and again during check-ins. The VSD also has information on race and ethnicity. In terms 

of stratifying analyses by race and ethnicity, VAERS is spontaneous reporting subject to 

reporting biases, so it is not necessarily representative of the population. V-safeSM is a voluntary 

self-enrollment system that may not be generalizable. Information is collected on race and 

ethnicity and that is analyzed, but they have to be careful about drawing conclusions from race 

and ethnicity in those two systems due to the limitations of the systems. Race and ethnicity are 

captured for VSD, so there is potentially an option to perform some population-based analyses. 

One limitation is that when the data are sliced very finely by age, vaccine, dose of vaccine, race, 

et cetera, the smaller the numbers which can lead to small numbers problems. It will definitely 

be possible to get participation rates form the v-safeSM system. It may not be representative, but 

it will be possible to know who is enrolling by race and ethnicity.
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Dr. Ault noted that being Black in America is a risk factor for pre-term births, but stillbirths and 

miscarriage have 15 to 20 recognized risk factors. One reason HCP were placed at the front of 

the line in the original recommendations was due to the concern for occupational exposure and 

because they are a very diverse and broad group, so this group is not skewed toward all upper 

SES statistics.

Ms. Léger (AAPA) noted that anecdotally, more women are reporting side effects after the 

second dose of mRNA vaccine.

Dr. Shimabukuro will take this information back to investigators performing the reactogenicity 

study in v-safeSM. This has been observed in the past, especially with VAERS reporting.

Dr. Daley asked whether the ability to monitor post-authorization safety of the Janssen vaccine 

might be more limited due to the fact that additional doses may not be quite as high as seen for 

Moderna and Pfizer in the first couple of weeks, and the visibility v-safeSM may be even lower if 

the Janssen vaccine is used in mass vaccination settings.

Dr. Shimabukuro said that while that may be possible, the intent is to conduct enhanced 

surveillance for the Janssen vaccine in VAERS. There are also some things that can be done in 

v-safeSM to get early quick visibility with the Janssen vaccine, such as overenrolling in the 

pregnancy registry to try to even out the numbers. For VAERS, the plan is to monitor the 

Janssen vaccine with the same intensity as the Pfizer and Moderna vaccines were monitored 

when those rolled out and in their initial weeks of vaccination.

Emerging SARS-CoV-2 Variants: Considerations for Vaccine

CDR Heather Scobie PhD, MPH

Center for Global Health

Centers for Disease Control and Prevention

Dr. Scobie reported that multiple SARS-CoV-2 variants are circulating globally. After emerging, 

some disappear and others persist. CDC and others are studying these variants to understand 

whether they spread more easily from person-to-person, cause milder or more severe disease 

in people, can be detected by available diagnostic tests, respond to therapeutics currently used 

to treat people for COVID-19, and/or change the effectiveness of COVID-19 vaccines. Based on 

the evidence, some variants are classified as “variants of concern” and appropriate public health 

actions are taken.56

Viruses constantly change through mutation, so new variants are to be expected. SARS-CoV-2 

has a low mutation rate compared with influenza and HIV. The drivers of evolutionary selection

are still being characterized but may include chronic infection (e.g., immunocompromised), 

interspecies transmission (e.g., minks), therapeutic treatment (e.g., monoclonal antibodies, 

convalescent sera), prior immunity to strains with limited cross-reactivity, increased

transmissibility, and founder effect in which a small number of genotypes seed a new population

by chance.

56 https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant.html;

https://www.who.int/publications/m/item/covid-19-weekly-epidemiological-update
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The D614G is an example of SARS-CoV-2 strain replacement. This variant was discovered in 

January 2020 and increased to almost 100% prevalence worldwide by June 2020. Compared 

with the ancestral strain, this variant has increased infectivity that has attributed to a more open 

conformation of the viral spike protein that helps it bind to host cells. The D614G variant likely 

has increased transmissibility giving it selective advantage, but it is not more clinically severe 

and current vaccines are still highly effective. This variant is not of particular concern, but it 

highlights the potential for similar replacements to occur with variants that may be more 

problematic.57

There are general concerns with 3 SARS-CoV-2 variants of concern as shown in the following 

table:

B.1.1.7 was first detected in the UK, B.1.351 was first detected in South Africa, and P.1 was first 

detected in Brazil and Japan. By now, these variants are being detected in many countries. Both 

B.1.1.7 and B.1.351 are estimated to be 50% more transmissible and have become the 

dominant strains in some areas. Each variant has 2 names, which adds confusion. The names 

point to the ancestry of the viruses and are recognizable because they contain periods. Another 

source of confusion is the many mutations under discussion. For instance, the abbreviation 

E484K means that an amino acid called glutamic acid (E) was replaced with a lysine (K) at 

position 484 in the spike protein, which is a negative to positive change that can be problematic 

if occurring in a key binding site. This will be important later on.

In terms of the US COVID-19 cases caused by variants of concern, 2400 cases have been 

detected of B.1.1.7 in 46 states, 53 cases of B1.351 have been detected in 16 states, and 10 

cases of P.1 have been detected in 5 states.58 B.1.1.7 was first detected in the US in December 

2020, but a study has shown that it likely arrived in November 2020 through multiple 

introductions. The current prevalence is estimated at 1% to 2%.

59 Commercial diagnostic data 

suggest that the US is in an early phase logistic expansion.

60 Two modeling studies suggest that 

57 Callaway E. Nature (2020). https://www.nature.com/articles/d41586-020-02544-6

Volz et al. Cell (2021). https://www.sciencedirect.com/science/article/pii/S0092867420315373

https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html#ref2

58 https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html (data as of 02/28/2021) 

59 https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html

60 Washington et al. medRxiv preprint (Feb 7 2021): https://www.medrxiv.org/content/10.1101/2021.02.06.21251159v1

 

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B.1.1.7 may predominate by late March 2021. One of the studies suggests that high vaccine 

coverage will blunt the public health impact of the variant’s higher transmissibility.

61

The receptor-binding domain (RBD) of spike protein binds the host ACE2 receptor, and 

interaction that is necessary for infection. For SARS-CoV-2, the majority of neutralizing 

antibodies bind the RBD, blocking this interaction and neutralizing the effect of the virus. 

Convergent evolution of different variants has revealed a cluster of several mutations in the 

RBD that increase the binding and infectivity and reduce the efficacy of antibody therapies. The 

mutations are N501Y, which occurs in all three variants, and E484K and K417N that occur in 

the South Africa and Brazil variants. This is illustrated in the following photograph:62

All of the variants of concern are distinguished by the large number of mutations that they have 

in their spike proteins. There is also another variant called P.2 that is the dominant strain in 

Brazil that has an E484K mutation, with fewer spike mutations overall.

In terms of the impact of these variants on vaccine effectiveness, 26 available studies were 

reviewed of vaccines authorized or intended to be authorized in the US containing data on the 

ability of post-vaccination sera to neutralize SARS-CoV-2 variants. There were 8 published 

studies and 18 pre-print studies, all of which had small sample sizes of less than 50 sera. 

Among the studies, 13 assessed only Pfizer vaccine, 3 assessed only Moderna vaccine, 2

assessed studies on AstraZeneca vaccine, 7 studies assessed more than one vaccine study, 

and 8 studies evaluated the effect of single or limited sets of mutations found in the variants and 

generally found minimal impact. Exceptions were E484K and the triple mutation in the receptor 

binding domain, E484K-K417N-N501Y, which had relatively large effects. The largest impacts

observed were for the B.1.351 (South Africa), followed by P.1, P.2 (Brazil), and then B.1.1.7 

(UK). In most studies, B.1.351 had a 3- to 11-fold reduction in neutralization, but ranged up to 

97-fold. Most B.1.1.7 studies generally had a less than 3-fold reduction, but ranged up to 9-fold. 

The threshold of concern for reduction in neutralization activity has not yet been established.

On average across the studies, B.1.351 had a larger reduction in neutralization than B.1.1.7. In 

the 2 variants from Brazil, P.1 and P.2 had an intermediate reduction within the few studies 

available. Several studies noted that a single E484K mutation could account for most of the 

61 Galloway et al. MMWR 2021;70:95–99. https://www.cdc.gov/mmwr/volumes/70/wr/mm7003e2.htm?s_cid=mm7003e2_w

62 https://www.nytimes.com/interactive/2021/health/coronavirus-variant-tracker.html
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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reduced neutralization of the South Africa and Brazil variants. One study assessed a B.1.1.7 

variant with an E484K change that has been detected in the UK and other countries and found 

that neutralization was substantively reduced compared to B.1.1.7. Five studies have shown 

that postponing the second mRNA dose may leave some people less protected against the 

SARS-CoV-2 variants. Normally, minimal or no neutralization against B.1.351 was observed 

after one mRNA vaccine dose. In a few studies, people who had recovered from COVID-19 and 

received one vaccine dose had moderate protection against B.1.351. All of the studies noted 

improved neutralization of B.1.1.7 and B.1.351 after the second vaccine dose. One Pfizer 

vaccine study noted delayed kinetics of the antibody response against the variants. Antibody 

responses to B.1.1.7 and B.1.351 at Week 2 after the first dose were reduced relative to the 

dominant D614G strain, but improved slightly by Week 3, especially for B.1.1.7. Both B.1.1.7 

and B.1.351 improved at Week 4 one week after the second dose. These results suggest that 

maturation of the immune response could be important in protecting against the variants.

It is difficult to estimate how laboratory results might translate to clinical protection, given that 

there is currently no immunological correlate of protection for SARS-CoV-2. In general, 

neutralization antibodies in sera from mRNA vaccine recipients have been shown to be higher 

than for COVID-19 convalescent sera. The variation in the results presented may be explained 

by differences in experimental conditions such as the type of neutralization assays used, 

differences in when and from whom the sera were collected, and whether recombinant viruses 

with limited or full sets of spike mutations were used versus viral clinical isolates. It is also 

important to note that the antigen used from the AstraZeneca vaccine is not the prefusion 

stabilized spike protein used in other authorized vaccines, so results with this vaccine may have 

limited generalizability to other vaccines. Limitation for all studies were small sample sizes and a 

lack generalizability. Many of the studies were pre-prints that had not yet been peer-reviewed.

Switching now to data from clinical studies of vaccine efficacy or effectiveness related to the 

variants, Dr. Scobie reviewed the point estimates in the following table with the caveats that this 

is a summary of the preliminary data available; most of it has not yet been peer-reviewed and it 

is not meant to compare across vaccines as the studies used different outcomes and occurred 

in different epidemiologic settings; and generating additional data on the relative vaccine 

effectiveness for each variant would be useful:

 

 

Dagan et al. EJM (2021https ). www.nejm.org doi full 1 0.10 6 EJMoa2101 6 ?query OC

https www.fda.gov media 14621 download

 ovava . https i r.novava .com news releases news release details novava covid 1 vaccine demonstrates 8 efficacy u k phase 

Madhi et almed iv . preprint (Feb 1 22021) https doi.org 1 0.1101 2021.0 2.1 0.212 124 

Emary et al. Lancet preprint (Feb 2021 4 ) https papers.ssrn.com sol papers.cfm?abstract i d 160

 a ine S e 

 i er Post EUA 86 in UK (predominate B.1.1. circulation) 

 4 in Israel (up to 80 of cases from B.1.1. )

Janssen Pre EUA 4 in U.S.

 66 in Brazil

 2 in S. Africa

 vava Pre EUA

Pre EUA

 6 against non B.1.1. in UK

 86 against B.1.1. in UK

 60 in S. Africa ( of cases from B.1. 1)

 s ra ene a Pre EUA

Pre EUA

 84 against non B.1.1. in UK

 against B.1.1. in UK

 10 against B.1. 1in South Africa

 

 
Advisory Committee on Immunization Practices (ACIP) Summary Report February 28-March 1, 2021

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In summary of the preliminary data, the B.1.1.7 variant is exponentially increasing in prevalence 

in the US, but has minimal impact on vaccine effectiveness. However, variants with additional 

substitutions in RBD, such as E484K, deserve special attention. The B.1.351 variant is currently 

at low prevalence in the US. It has moderate impact on vaccine effectiveness, suggesting that it 

would be prudent to start evaluating variant vaccines in case prevalence begins to substantially 

increase. The P.1 variant has very low prevalence in the US, but has the same triple mediation 

in the RBD as B.1.351, which is worth watching closely. Additional data are still needed on the 

potential impact on vaccine effectiveness. It is important to emphasize that the current 

prevention measures and authorized vaccines offer good protection against SARS-CoV-2 

variants. Efforts are needed to increase the speed and degree of uptake. Periodic updating of 

SARS-CoV-2 vaccines likely will be needed. One modeling study63 has predicted that changing 

COVID-19 vaccines to target faster spreading viral variants will be more effective than targeting 

the slower dominant strain, despite initial prevalence.

Regarding the response to variants, the SARS-CoV-2 Interagency Group (SIG) was established 

by the HHS to improve coordination among several agencies, including: CDC, NIH, FDA, 

Biomedical Advanced Research and Development Authority (BARDA), US Department of 

Agriculture (USDA), and Department of Defense (DoD). The SIG focuses on rapid 

characterization of emerging variants and monitors the potential impact on SARS-CoV-2 

diagnostics, therapeutics, and vaccines.

64

CDC is undertaking a number of efforts to improve genomic surveillance and epidemiology that 

are relevant for monitoring the variants 65. As part of the National SARS-CoV-2 Strain 

Surveillance (NS3), CDC process approximately 3,000 random specimens per month from 

public health laboratories across the US. CDC also has partnered with commercial diagnostic 

laboratories to sequence and addition 6,000 specimens per week. CDC also contracts and 

partnerships with state and local health departments and universities to conduct genomic 

surveillance.66 In addition, CDC leads the SARS-CoV-2 Sequencing for Public Health 

Emergency Response, Epidemiology, and Surveillance (SPHERES) Consortium67 that includes 

approximately 170 domestic partners and facilitates the open sharing of SARS-CoV-2 

sequencing data. CDC also conducts focused molecular epidemiologic studies that are relevant 

to characterizing the variants. This chart shows the cumulative number of published SARS-CoV2 sequences by collection data from laboratories across the US beginning in January 2020 to 

the present:

63 Bedwick et al. medRxiv preprint (Feb 8 2021); doi: https://doi.org/10.1101/2021.01.05.21249255

64 Walensky, Walke and Fauci. JAMA (2021): https://jamanetwork.com/journals/jama/fullarticle/2776739

65 https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance.html

66 https://www.aphl.org/programs/preparedness/Crisis-Management/COVID-19-Response/Pages/Sequence-Based-Surveillance

Submission.aspx

67 https://www.cdc.gov/coronavirus/2019-ncov/covid-data/spheres.html
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Despite high vaccine efficacy, vaccine breakthrough cases are still expected to occur. Some will 

be caused by the variants even if the vaccine has similar effectiveness against the variants. A 

vaccine breakthrough case is defined as “a person with SARS-CoV-2 RNA or antigen detected 

in a respiratory specimen collected at least 14 days after completing the primary series of an 

FDA-authorized COVID-19 vaccine. Cases are identified from the national case-based 

surveillance, VAERS, health departments, and healthcare providers. CDC works with state 

health departments on case investigations. Available respiratory specimens are used for whole 

genome sequencing (WGS) to identify variants. Data from investigations will be posted or 

published when available.

Moderna and Pfizer have announced that they are launching booster studies of current vaccines 

in the US68 and are also developing second-generation vaccines against B.1.351. Moderna’s 

published strategy includes testing a vaccine specific to the South Africa variant and a 

multivalent vaccine that combines the previously authorized vaccine for the ancestral strain and 

the new vaccine for the variant. Still yet to be defined is the framework of evidence indicating

the need for a modified vaccine and the process for evaluating, deciding, and recommending 

whether a modified vaccine is needed. The World Health Organization (WHO) likely will have a 

role in global coordination and is developing a risk assessment framework.

68 https://investors.modernatx.com/news-releases/news-release-details/moderna-covid-19-vaccine-retains-neutralizing-activityagainst;

https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-it-has-shipped-variant-specificvaccine; 

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-initiate-study-part-broad-development

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
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The FDA recently published guidance on the evidence needed to support an EUA amendment 

for vaccines addressing the emerging SARS-CoV-2 variants.

69 The required evidence includes 

the following:

1. Good manufacturing practices and controls

2. Nonclinical data (e.g., laboratory studies, animal models)

3. Clinical data from immunogenicity studies — noninferiority with authorized vaccine

– Primary series or booster dose

– Could be single age group with extrapolation to other age groups

– Safety data from during the immunogenicity evaluation period

4. Laboratory assays and immunogenicity endpoints

– Correlates of protection not yet established

In closing, CDC will continue to monitor evidence on the emergence and spread of SARS-CoV2 variants, vaccine effectiveness, breakthrough infections in vaccinated or previously infected 

persons, and the ability of post-vaccination serum to neutralize emerging variant viruses. The 

COVID-19 Vaccines WG and ACIP will review evidence submitted for any next generation 

vaccines if it becomes clear that they are needed to address variants.

Discussion Points

Dr. Romero asked what is known about recombination and whether it plays a role in the 

development and transmission of new mutations.

Dr. Scobie pointed out that SARS-CoV-2 does not have a segmented genome unlike influenza 

for which this is a major source of variant generation. It is possible for SARS-CoV-2, but it is not 

clear that this is a major source of evolutionary variation. 

Dr. Romero noted that for poliovirus, the RNA will slip down, jump off, and move on to another 

virus.

Dr. Scobie replied that she has seen a few papers that mention that this may be the case, but it 

does not seem to be a major source of introduction of mutation. She called upon someone from 

the laboratory to comment further.

Dr. Wentworth added that it is a good question. RNA recombination is seen in coronaviruses, 

but it has not been observed to drive the evolution of the variants. These variants have evolved 

independently in a linear sense across the genome as point mutations that have occurred and 

then develop further point mutations. When so many mutations are occurring at the same time 

such as in the 351 variant, recombination cannot be ruled out. However, there is no evidence of 

that at this point. That would be intraspike recombination events. Usually with coronaviruses, 

the recombination is everything 3 prime to some point downstream and it is easy to see.

Dr. Maldonado (AAP) pointed out that recombination events are quite frequent with RNA 

viruses. For example, they occur on a regular basis with polioviruses and are usually not 

canonical so they can happen at any point. There are some recent non-peer-reviewed papers 

suggesting that there are combinations that can occur. While these are different, it is not 

insignificant.

69 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-vaccines-prevent-covid19
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Dr. Zahn (NACCHO) commented that from a local public health level, it would be great to have 

a sense of a variant before it becomes a variant of concern. They have had the experience in 

California with researchers identifying new strains that may be reported in the local media and 

the literature and there may be speculation as to how important these news strains are, whether 

they are more infectious, whether they change the epidemiology, and so forth. When they are 

asked about this by local and state public health, it would be beneficial in terms of 

communication to have a roadmap to describe how these events are being assessed.

Dr. MacNeil indicated that this is a very active and ongoing discussion. From the USG 

standpoint, definitions are being developed that are in the interagency phase. CDC is also 

assessing this internally to make decisions about what constitutes a variant of concern. A clear 

definition is needed. Some of the key criteria that go into this include evidence of the virus 

having immune escape, evidence of convergent evolution, the potential impact of diagnostics or 

therapeutics, or evidence of increased transmissibility or disease severity.

Dr. Goldman (ACP) inquired as to whether the reason is known for Florida’s seemingly 

disproportionate number of variants.

Dr. MacNeil replied that with regard to B.1.1.7, early on there were a number of different 

diagnostic PCR assays that were indicative of the deletion of amino acids 69 and 70. Early on 

using the S-Gene Target Failure (SGTF) screening assay, there were attempts to try to rapidly 

identify circulation of B.1.1.7, which somewhat depended on which diagnostic laboratory was 

involved. There was a natural concentration in terms of certain states and enrichment of B.1.1.7. 

That said, in addition to maybe some skewing of the data, there probably is increasing 

transmission in Florida. It may be partly artifactual, but there is evidence of the virus continuing 

to become more prevalent. Also related is that given the evidence that B.1.1.7 has a higher 

reproductive number, once a critical point of growth of that variant is reached, the variant’s 

share is exponential. It may be partly a founder effect where a state like Florida had earlier 

introductions enough that it started the exponential growth phase.

Dr. Kimberlin (AAP Redbook) recalled that slide 20 mentioned that the AZ vaccine being studied 

in the time at South Africa was not a prefusion stabilized spike protein, which therefore limited 

generalizability to other vaccines. He inquired as to whether the mRNA vaccines and the 

Janssen vaccine are prefusion stabilized spike proteins and if the AZ vaccine was unique in not 

being a prefusion stabilized spike protein vaccine among the 3 currently authorized vaccines. 

Dr. Scobie confirmed that this was her understanding.

Dr. Kotton expressed gratitude for mention of immunocompromised hosts as an area of 

emerging interest. As someone who cares for many immunocompromised hosts, she is seeing 

an increased rate of refractory disease with months of infection and disease. She is very 

concerned that this may serve as an important reservoir for multiple mutations and potentially 

nosocomial transmissions, et cetera. She asked whether this would be an area of focus for 

vaccinations and/or research, given that this could be the most significant problem population.

Dr. Wentworth indicated that while there are not particular laboratory studies geared toward this 

at present, he agreed that this is an important population. There are specific cases periodically 

in which people refer to the CDC about a long-term shedder in whom infection cannot be 

resolved.
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Dr. MacNeil added that he is not aware of any studies specifically focused on 

immunocompromised individuals. He agreed with the importance of this point and noted that 

this was one of the prevailing hypotheses behind the emergence of B.1.351 and the fact that 

quite a number of mutations emerged within a single variant. It is possible that 

immunocompromised individuals in essence shed for a long period of time, which will allow the 

virus to acquire quite a number of mutations. There may be an opportunity in locations where 

there is a high prevalence of HIV-positive individuals to conduct enhanced or further 

surveillance.

Dr. Kotton added for the record that she meant immunocompromised in general and not as 

much HIV as patients on rituximab and other potent immunosuppression. While they are not 

currently referring these cases to CDC, that could be done on a large scale. The 

immunocompromised host clinicians would need to be informed about that.

Regarding the emergence of the UK variant, Dr. Sanchez noted that a lot has been said about 

the UK delaying the second dose and he wondered whether any studies had examined the 

potential relationship between delay of the second dose and emergence of variants. He 

emphasized that Dr. Scobie’s presentation seemed to clearly answer the question posed by the 

first presentation of the day about whether to continue with the 2-dose regimen without delay of 

the second dose.

Dr. Scobie clarified that sequentially, B.1.1.7 did arise and become prevalent before the delay in 

the second dose became a policy. She was not aware of any studies assessing the delay of the 

second dose, but quite a few studies are being published in the literature now on the real-world 

vaccine efficacy of 1 dose. She thought those were used as the rationale to support the policy in 

the UK. It is a good question and the more conservative approach is to follow the current 

recommendation in terms of the 2-dose series.

Dr. Long wondered whether there is any signal that children are affected differently with the 

mutant variants. She emphasized that pediatricians are concerned about the next respiratory 

season. It is not clear from whence comes the blessing that children seem to be less affected by 

SARS-CoV-2, but everyone is concerned that if part of the explanation is some cross-protection 

or being primed with other coronaviruses, it is going to be a very complicated next winter when 

there have not been any respiratory viruses such that there will be a double group experiencing 

their first influenza, respiratory syncytial virus (RSV), and potentially children who have not seen 

coronavirus. It will be important to understand the genetics of the organisms that have caused 

disease in children.

Dr. MacNeil indicated that the overall prevailing thought in general outside of B.1.1.7 is that 

these variants do not have differing impact on clinical outcomes. There are some data that have 

not yet been published from reports on a UK study that B.1.1.7 may be more associated with 

increased severity in terms of hospitalizations and deaths. However, he was not aware of any 

evidence as this point specific to children and differences in terms of outcomes.

Dr. Gluckman (AHIP) asked whether there is any idea about what the speed to market will be 

for the development of second generation Pfizer and Moderna vaccines, and whether it will be 

important to have consistency in the platform for whatever a patient received with first 

generation vaccines. That is, if their primary vaccine was with an mRNA vaccine any second 

generation vaccination also should be with an mRNA vaccine.
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Dr. Oliver responded that they are going to have to wait to see what the development speed and 

recommendations will be. As mentioned before, FDA is laying the groundwork for how this 

would work. CDC would wait for data to be submitted to FDA and then bring those data to ACIP

for future discussion and recommendations. As has been publicly stated, Moderna has indicated 

that they will be starting trials soon with the variant vaccines. CDC will keep ACIP updated on 

these vaccines moving forward.

Dr. Duchin (NACCHO) noted that it seems with the predicted prevalence of B.1.1.7 in the US 

and the increasing recognition of other variants, the US remains vulnerable to a potentially 

severe fourth wave of this COVID-19 pandemic. It is clear that vaccines ultimately will be the 

best weapon against COVID-19 and its variants, but it is important in this discussion to 

recognize that it cannot be the only strategy at this point. They must reinforce the importance of 

other COVID-19 prevention measures at this time, including limiting activities, well-fit and wellmaintained face masks, good ventilation, avoiding crowded indoor spaces, et cetera. He noticed 

that one slide mentioned that high vaccine coverage will blunt the impact of higher 

transmissibility. Clearly, the more people who are vaccinated the more who are protected. He 

requested further comment on what “high vaccine coverage” meant in this context.

Dr. MacNeil indicated that the modeling team set up dynamic models for this, which he thought 

was based on vaccine coverage increasing over time. He did not immediately recall the 

assumptions, he noted that the study is published in the MMWR.

Dr. Weiser (IHS) asked about the completeness of the surveillance systems, particularly for 

rural areas. Related to that, he wondered who they should contact if interested in participating.

Dr. MacNeil acknowledged that representativeness is certainly a challenge, particularly for a

large proportion of the pandemic during which there was reliance primarily on platforms that 

involved crowd sourcing of sequencing. As Dr. Scobie mentioned earlier, CDC has taken on a 

couple of initiatives to try to scale up the number of sequences and the representativeness of 

these. This includes the NS3 surveillance that functions through CDC’s state and jurisdictional 

public health laboratories as well as trying to generate sequences across the board from large

number of specimens from commercial laboratories. He thinks they are getting much closer to 

being representative and in having a denominator in which they can be confident enough to 

begin generating representative prevalence estimates. That should be coming out soon. In 

terms of participating, NS3 is functioning through state and jurisdictional public health 

laboratories. Working with them would be the way to operate through NS3. There are a number 

of other sequencing efforts through state and local public health laboratories and academic 

partners. As much data as they can get in the public space is going to be helpful and will 

contribute to the overall understanding of the viruses that are circulating.

Dr. Arthur (BIO) suggested that it might also be beneficial for the ACIP to review the emerging 

data on the use of monoclonal antibodies in the preventive space, which could add some 

complexity to the discussion about prevention, particularly in the presence of variants. Some of 

the preliminary data are quite strong and might be worthwhile to provide an opportunity for the 

ACIP WG and members to review those data as they start to roll out.

Dr. Maldonado (AAP) suggested that it might be helpful for ACIP to hear a presentation on how 

the variants that recently have been circulating impact transmission and the concept of herd 

immunity based on current models.
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Upon reviewing the foregoing version of the February 28-March 1, 2021 ACIP meeting minutes, 

Dr. Jose Romero, ACIP Chair, certified that to the best of his knowledge, they are accurate and 

complete. His original, signed certification is on file with the Management Analysis and Services 

Office (MASO) of CDC.

Certification
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Department of Health and Human Services 

Centers for Disease Control and Prevention 

Advisory Committee on Immunization Practices 

December 23, 2020 – June 30, 2021 

CHAIR

ROMERO, José R, MD, FAAP 

Arkansas Secretary of Health 

Director, Arkansas Department of Health 

Professor of Pediatrics, Pediatric Infectious Diseases 

University of Arkansas for Medical Sciences 

Little Rock, Arkansas 

Term: 10/30/2018-06/30/2021 

EXECUTIVE SECRETARY

COHN, Amanda, MD 

Senior Advisor for Vaccines 

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 

ACIP Membership Roster
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BERNSTEIN, Henry, DO, MHCM, FAAP 

Professor of Pediatrics 

Zucker School of Medicine at Hofstra/Northwell 

Cohen Children’s Medical Center 

New Hyde Park, NY 

Term: 11/27/2017-06/30/2021 

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 

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 

FREY, Sharon E, MD 

Professor and Associate Director of Clinical Research 

Clinical Director, Center for Vaccine Development 

Division of Infectious Diseases, Allergy and Immunology 

Saint Louis University Medical School 

Saint Louis, MO 

Term: 11/27/2017-06/30/2021 

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 

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: 7/1/2016 – 6/30/2021 
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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 

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 – ationwide 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 
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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 

Indian Health Service (IHS) 

WEISER, Thomas, MD, MPH 

Medical Epidemiologist 

Portland Area Indian Health Service 

Portland, OR 

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 
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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 

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 
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American Geriatrics Society (AGS) 

SCHMADER, Kenneth, MD 

Professor of Medicine-Geriatrics Geriatrics 

Division Chief 

Duke University and Durham VA Medical Centers 

Durham, NC 

 eri a’s eal ns ran e lans 

GLUCKMAN, Robert A, MD, MACP 

Chief Medical Officer, Providence Health Plans 

Beaverton, OR 

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) 

FOSTER, Stephan L, PharmD CAPT 

(Ret) USPHS 

Professor, College of Pharmacy 

University of Tennessee Health Sciences Center 

Memphis, TN 

Association of Immunization Managers (AIM) 

HOWELL, Molly, MPH 

Immunization Program Manager 

North Dakota Department of Health

Bismarck, ND 
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Association for Prevention Teaching and Research (APTR) 

McKINNEY, W Paul, MD 

Professor and Associate Dean 

University of Louisville School of Public Health and Information Sciences

Louisville, KY 

Association of State and Territorial Health Officials (ASTHO) 

SHAH, Nirav D, MD, JD 

Director

Maine Center for Disease Control and Prevention

Augusta, ME 

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) 

QUACH, Caroline, MD, MSc 

Pediatric Infectious Disease Specialist and Medical Microbiologist 

Medical Lead, Infection Prevention and Control Unit 

Medical Co-director – Laboratory Medicine, Optilab 

Montreal-CHUM 

Montreal, Québec, Canada 

Infectious Diseases Society of America (IDSA) 

BAKER, Carol J., MD 

Professor of Pediatrics 

Molecular Virology and Microbiology 

Baylor College of Medicine 

Houston, TX 
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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 

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 
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Pediatric Infectious Diseases Society (PIDS) 

O’LEA , 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 

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