COVID-19 Vaccine Safety Technical (VaST) 

Work Group 

Safety Assessments 

H. Keipp Talbot, MD MPH (VaST Chair)

Robert H. Hopkins, Jr., MD (NVAC Chair)

Advisory Committee on Immunization Practices

October 21, 2021
Topics 

 VaST objectives and activities

 Brief overview of selected Moderna and Janssen COVID-19 

vaccination safety data

 VaST assessments 

– Moderna COVID-19 vaccination 

– Janssen COVID-19 vaccination

– Heterologous boosting

 VaST future plans

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COVID-19 Vaccine Safety Technical (VaST) Work Group

Objectives

 Review, evaluate, and interpret post-authorization/approval COVID-19 

vaccination safety data

 Serve as the central hub for technical subject matter expertise from 

federal agencies conducting post-authorization/approval safety 

monitoring

 Advise on analyses, interpretation, and data presentation

 Provide updates to the ACIP COVID-19 Vaccines Work Group and the ACIP 

on COVID-19 vaccine safety

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VaST continues to review COVID-19 vaccination safety 

data from passive and active surveillance systems

 U.S. safety monitoring systems including Vaccine Adverse Events 

Reporting System (VAERS), Vaccine Safety Datalink (VSD), FDA BEST 

System,1 VA, IHS, DoD

 Israel, Canada, Global Advisory Committee on Vaccine Safety

 Special evaluations underway, such as follow-up studies of myocarditis 

cases

1https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/cber-biologics-effectiveness-and-safety-best-system

VA, Veterans Affairs; IHS, Indian Health Service; DoD, Department of Defense

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VaST activities

Dec 12 

Pfizer

(16+)

Feb 28 

Janssen 

(18+)

Apr 14 

CVST 

following 

Janssen

Dec 19 

Moderna

(18+)

Apr 23 

TTS updates; 

Janssen resumed

December 21, 2020 – present

38 independent meetings to review vaccine safety data

10 joint meetings with COVID-19 Vaccines Work Group focused on safety

Jan 27

Anaphylaxis 

following 

mRNA 

vaccination

Mar 1

Anaphylaxis 

updates;

Pregnancy 

vaccine safety 

data

ACIP 

votes

VaST 

assessments 

at ACIP 

meetings or 

website

CVST, cerebral venous sinus thrombosis; TTS, thrombosis with thrombocytopenia syndrome; GBS, Guillain-Barré syndrome 5

Dec Jan Feb March April May

May 12 

Pfizer

(12-15)

May 12

TTS 

updates

May 17 & 24

Myocarditis
VaST activities

December 21, 2020 – present (continued)

38 independent meetings to review vaccine safety data

10 joint meetings with COVID-19 Vaccines Work Group focused on safety

Jun 23

Myocarditis 

updates

ACIP 

votes

VaST 

assessments 

at ACIP 

meetings or 

website

CVST, cerebral venous sinus thrombosis; TTS, thrombosis with thrombocytopenia syndrome; GBS, Guillain-Barré syndrome 

July 22

GBS 

following

Janssen

Aug 13

Additional mRNA 

vaccine doses for 

immunocompromised

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Aug 30

Pfizer BLA 

(16+)

Aug 30

Safety 

overview

Sept 23

3rd dose

Pfizer

Sept 22

Pfizer 

3rd dose

June July Aug Sept Oct

Oct 21

Moderna 3rd dose

Janssen 2nd dose

Oct 21

3rd dose

Pfizer 

2nd dose 

Janssen
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 Myocarditis following mRNA COVID-19 vaccination identified, May 20211

 CDC issued clinical guidance for myocarditis/pericarditis following mRNA 

vaccination, May 2021

 Data presented at the VRBPAC meeting, June 10

 Data and VaST assessment presented to ACIP June 232 and MMWR published

 EUA fact sheets revised with warning added, June 25

 FDA approval of Pfizer BioNTech COVID-19 vaccine, August 23

– Information on myocarditis/pericarditis in package insert3

VRBPAC, Vaccines and Related Biologics Products Advisory Committee 

1https://www.cdc.gov/vaccines/acip/work-groups-vast/index.html; 2https://www.cdc.gov/vaccines/acip/meetings/slides-2021-06.htm;

3https://www.fda.gov/media/151707/download

Moderna COVID-19 vaccination: Overview of postauthorization safety – myocarditis/pericarditis
Moderna COVID-19 vaccination: Overview of postauthorization safety – myocarditis/pericarditis

 Data available to date show association of myocarditis with both mRNA vaccines in 

adolescents and young adults, males > females

– Some systems show greater risk after Moderna than Pfizer vaccination

• United States (VSD), Canada, Scandinavian countries

– Other U.S. safety monitoring systems do not show a difference between the 

two mRNA vaccines

• VAERS, FDA BEST Systems, VA

 Further data are being compiled to understand 

– Differences between safety systems

– Optimal management strategies

– Long-term outcomes 

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Moderna COVID-19 vaccination safety data, dose 3

 Clinical trial data – 50 μg dose in 171 participants*

– No evidence of increased reactogenicity following a booster dose relative to 

dose 2, with exception of increased axillary swelling/tenderness of the 

vaccination arm1

 Post-authorization safety data for Moderna dose 3, original 100 μg dose2

– v-safe: ~14,000 persons who reported dose 3

• Local reactions were reported slightly more frequently and systemic 

reactions slightly less frequently following dose 3 than dose 2

– VAERS: 1,440 reports after dose 3

• Over 92% of reports were non-serious

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1https://www.fda.gov/media/153087/download 2Hause A, ACIP October 21, 2021 

*participants who received 100 μg primary series; total 344 received 50 μg booster
 TTS1

– Surveillance in VAERS identified reports of CVST and TTS

– Use of vaccine in the United States was paused April 13 

– EUA fact sheets updated with warning about TTS, pause was lifted April 23

– Through October 13, 47 cases of TTS confirmed (15.3 M doses administered)

• Most cases in women, aged 18-49 years; evaluation ongoing 

 GBS2

– Surveillance in VAERS identified reports of GBS

– Higher than expected reporting, males > females; EUA fact sheets updated 

with information about observed risk, July 12

– Through July 24, 130 reports of GBS identified

• Observed reports > expected across multiple age groups

CVST: cerebral venous sinus thrombosis; TTS; thrombosis with thrombocytopenia syndrome; GBS, Guillain Barre Syndrome; 

1 Shimabukuro T, ACIP October 21, 2021; 2https://www.fda.gov/media/153132/download 10

Janssen COVID-19 vaccination: Overview of postauthorization safety, TTS and GBS
Janssen COVID-19 vaccination safety data – dose 2 

 Clinical trial data1

– Approximately 9,000 participants received 2 doses at least 2 months apart; 

approximately 2,700 have had at least 2 months of safety follow-up

– No new safety signals identified following a second dose.

– Interpretation of the data is limited by small sample size, particularly for 6-month 

interval post dose 1

 Post-authorization safety data2

– v-safe

• 83 participants recorded dose 2

– VAERS

• 39 reports after dose 2

• All reports were non-serious

1https://www.fda.gov/media/153130/download and https://www.fda.gov/media/153129/download ; 2Hause A, ACIP October 21, 2021
VaST assessment summary – primary series

 Moderna COVID-19 vaccination

– There appears to be a slightly increased risk of myocarditis among 18–39 

year-olds after Moderna compared with Pfizer vaccination

– Preliminary data from follow-up study, based on data from patients/parents, 

suggest that cases are generally mild, with prompt resolution of symptoms 1

 Janssen COVID-19 vaccination

– Risks for TTS and GBS appear to be unchanged from earlier assessments –

serious but rare 

 Important to communicate to public and patients the balance of benefits 

and risks

1 Follow-up being conducted for confirmed myocarditis cases after COVID-19 vaccination reported to VAERS 12
VaST assessment summary – booster doses 

 Moderna COVID-19 vaccination

– Limited data on risk of myocarditis after dose 3 (original 100 μg dose) from 

safety monitoring systems

– Data on safety of the reduced 50 μg booster dose only available from small 

clinical trial

– Risk of myocarditis observed following the reduced dose Moderna booster 

might be lower than risk following the original dose vaccination 

 Janssen COVID-19 vaccination

– Limited trial data and data from safety monitoring systems for dose 2

– Risks after booster dose are unlikely to be greater than with primary vaccination 

 Important to communicate to public and patients the balance of benefits and risks

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VaST assessment summary – heterologous booster

 Preliminary data from NIH mix and match study1 and limited data from 

post authorization safety data suggest that boosting of Janssen COVID-19 

vaccine recipients with an mRNA vaccine, or of mRNA COVID-19 vaccine 

recipients with Janssen COVID-19 vaccine poses no additional safety risk 

compared with homologous boosting

 No evidence to date of safety concerns with respect to any of the 

prespecified VSD surveillance outcomes for Janssen COVID-19 vaccine 

recipients who received an additional dose of an mRNA COVID-19 vaccine 

14 1 Atmar R, ACIP October 21, 2021
Safety monitoring and VaST next steps

 VaST will continue to:

– Review safety regarding additional and booster doses as data 

become available

– Collaborate with global vaccine safety colleagues on key issues that 

impact benefit-risk balance

– Provide updates to the ACIP COVID-19 Vaccines Work Group and the 

ACIP at future meetings

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VaST Members

VaST Members

Keipp Talbot (ACIP)

Robert Hopkins (NVAC)

Matt Daley

Grace Lee

Veronica McNally

Kathy Edwards

Lisa Jackson

Jennifer Nelson

Laura Riley

Robert Schechter

Patricia Whitley-Williams

CDC Co-Leads

Lauri Markowitz

Melinda Wharton

Ex Officio and Liaison Representatives 

Tatiana Beresnev (NIH)

Karen Farizo; Hui Lee Wong (FDA)

Judith Steinberg (OIDP)

Jeffrey Kelman (CMS)

Matthew Clark (IHS)

Mary Rubin (HRSA)

Fran Cunningham (VA)

Limone Collins (DoD)

Administrative Support

Jared Woo

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