National Center for Emerging and Zoonotic Infectious Diseases

JYNNEOS Vaccine Safety Monitoring During tMpox Outbreak ─ United States Jonathan Duffy, MD, MPHImmunization Safety OfficeCenters for Disease Control and PreventionAdvisory Committee on Immunization PracticesFebruary 22, 2023
CDC Mpox vaccine safety data sources

 Vaccine Adverse Event Reporting System (VAERS) Vaccine Safety Datalink (VSD) V-safe after vaccination health checker Single-patient emergency Investigational New Drug (EIND) pr
VAERS
VAERS is the nation’s early warning system fo

safety
JYNNEOS EUA* required reporting to VAERS f

adverse events and vaccine administration er

 The vaccination provider is responsible for MANDATORY repo

following listed events following JYNNEOS to VAERS:

– Vaccine administration errors whether or not associated 

adverse event

– Serious adverse events (irrespective of attribution to vac– Cases of cardiac events including myocarditis and pericar– Cases of thromboembolic events and neurovascular even

*EUA indications: intradermal injection for individuals aged ≥18 and subcutaneous injection for individuals agfor Healthcare Providers Administering Vaccine: Emergency Use Authorization of Jynneos (Smallpox Vaccine, Live, Non-Replicating) for Prevention of Monkeypox Disease in Individuals Determined to be Monkeypox Infection (fda.gov)
VAERS: JYNNEOS surveillance methods

 VAERS reports received and processed by January 20, 2023 Adverse event reporting rates were calculated by dividing the 

VAERS reports by the number of vaccine doses administered 

– Vaccine doses administered during May 22–January 13 a

CDC by January 23, 2023

• Dose 1: 698,188• Dose 2: 426,980• Total: 1,125,168
VAERS: JYNNEOS report characteristics, n = 1,8

Characteristic n (%)

Sex

Male 1,415 (78)Female 238 (13)Not reported 164 (9)

Age

0-17 25 (1)18-64 1,501 (83)≥65 83 (5)Not reported 208 (11)

Other vaccines on same day

Yes 45 (2)No 1,772 (98)

Characteristic 

Dose in series

1 2 Not reported 

Route of administration

Intradermal Subcutaneous Intramuscular 

Not reported 
VAERS: vaccine administration error reports

 Represent 50% of all JYNNEOS VAERS reports

– Of these, 96% did not report an adverse health even

t

 Error reporting rate

– Intradermal: 937 per million doses administered– Subcutaneous: 306 per million doses administered

 Errors frequently reported with attempted intradermal admin

– Absence of a wheal without vaccine leakage (42%)– Vaccine leakage from injection site (12%)
VAERS: adverse health event reporting rates p

million doses administered by route of admin

Intradermal 

All adverse health events Injection site erythema Dizziness Injection site swelling Urticaria Injection site pruritus Erythema Syncope Pruritus Hyperhidrosis Loss of consciousness 

Subcutaneous rate

All adverse health events 639Injection site erythema 107Injection site swelling 107Injection site pain 99Pain 96Fatigue 80Erythema 77Headache 77Dizziness 74Injection site pruritus 66Pyrexia 66
Serious Adverse Event definition

 Death A life-threatening adverse event Inpatient hospitalization or prolongation of existing hospitaliz A persistent or significant incapacity or substantial disruption 

to conduct normal life functions

 A congenital anomaly/birth defect An important medical event that based on appropriate medic

may jeopardize the individual and may require medical or surintervention to prevent one of the outcomes listed above
VAERS: serious adverse events reported after 

n = 26 Myocarditis (n=5) Death (n=2)** Pericarditis (n=2) Urticaria (n=2) Appendicitis Aseptic meningitis Asthenia Atrial fibrillation Cellulitis Chest pain

 Dehydration Idiopathic thromb

purpura 

 Injection site disco Injection site pain Injection site scar Methemoglobinem Retrograde amnes Rhabdomyolysis Sudden hearing lo

SAE reporting rate: 22 reports per million doses admini

*The report of an adverse event to VAERS is not documentation that a vaccine caused the event.**Reported causes of death: drowning, cocaine toxicity.
Myocarditis and pericarditis
Myocarditis and pericarditis

 Myocarditis and pericarditis have occurred following either p

vaccination or revaccination with live vaccinia virus smallpox 

– The mechanism is poorly understood, and it was unknow

persons who receive JYNNEOS might experience myocardpericarditis

 Epidemiologic analysis groupings:

– Myocarditis with or without pericarditis– Pericarditis

 Surveillance risk interval: symptom onset within 30 days afte

Case definitions available at: DOI: 10.15585/mmwr.mm7027e2
Myocarditis rate per million persons during 30-day p

Observed after JYNNEOSExpected Historical myocarditis population background rates per millio

– U.S. military in 2002

1: 21.6

– MarketScan database, males 18–64 yrs in 2017–2019

2: 2.7 – 7.

 Historical myocarditis rates after live, replicating smallpox vac

or ACAM2000) ranged from 78 to 5,230 cases per million per

Data source

Dose 1

cases doses

rate per million

(95% CI)

Dose 2

cases doses

VAERS 2 726,851 2.75 (0.33–9.94) 3 445,019 Vaccine Safety Datalink

1 37,646 27 (0.67–148) 1 21,919 

References:1) Halsell, et all. DOI: 10.1001/jama.289.24.3283; 2) Oster, et al. DOI: 10.1001/jama.2021.24110 ;

3) Mandra, et al. DOI: 10.1017/dmp.2020.478
Pericarditis rate per million persons during 30-day p

Observed after JYNNEOSExpected Historical pericarditis population background rates per millio

– Italy, 2001–2005

1: 22.8

– U.S. Nationwide Inpatient Sample database, 2003–201

2

2: 4.7

 Historical pericarditis rate after live, replicating smallpox vacc

or ACAM2000) was 925 cases per million persons in one U.S. 

Data source

Dose 1

cases doses

rate per million

(95% CI)

Dose 2

cases doses

VAERS 4 726,851 5.50 (1.50–14) 2 445,019 Vaccine Safety Datalink

0 37,646 0 0 21,919 

References:1) Imazio, et al. DOI: 10.1136/hrt.2006.104067; 2) Kumar, et al. DOI: 10.1159/000445206;3) Engler, et al. DOI:10.1371/journal.pone.0118283
V-safe
V-safe Mpox: active vaccine safety monitorin

 Smartphone-based system that uses text messaging to initiate w

survey monitoring for adverse events following vaccination

 V-safe is used to:

– Characterize the basic safety profile of a vaccine when given 

clinical trial setting

– Provide information for public health communication around – Facilitate reporting to the Vaccine Adverse Event Reporting S

for medically attended adverse events following vaccination

 V-safe supplements CDC’s other vaccine safety monitoring system

Vaccine Safety Datalink (VSD)
V-safe Mpox: characteristics of active particip

Characteristic N=181

n (%)

Age in years

18-49 112 (61.9)50-64 56 (30.9)≥65 13 (7.2)

Gender identity

Male 139 (76.8)Female 28 (15.5)

Transgender 7 (3.9)

None of the above or unknown

7 (3.9)

Immunocompromised** 32 (17.1)

Characteristic Race/Ethnicity

White, non-Hispanic 

Hispanic Asian, non-Hispanic Black, non-Hispanic Multiracial, non-Hispanic Other race, non-Hispanic Unknown race or ethnicity 

*active participants defined as having survey, November 16, 2022 – January **defined as self-report of immunocotaking immunosuppressive medicatio
V-safe Mpox: reactions and health impact events reported by v

participants at least once in days 0-7 after vaccination, by dose

81

62

26

19

14

80

54

16 14

10

0

102030405060708090

100

Any injection site reaction Any systemic reaction Any health impact Unable to perform normal

daily activities

Unable to work or atten

school

Percentage

Dose 1 Dose 2

Includes 42 participants who completed at least one survey after dose 1 and 50 participants who completed at leafter dose 2, data collected November 16, 2022 – January 29, 2023
V-safe Mpox: top injection site and systemic reactions reported 

participants at least once in days 0-7 after Mpox vaccination, b

62

55 52 50

40

24 24 24

64

54

46

40 42

28 26

22

0

102030405060708090

100

Redness at site Itching at site Lump at site Swelling at site Fatigue Headache Pain at site Myalgia 

Percentage

Dose 1 Dose 2

Includes 42 participants who completed at least one survey after dose 1 and 50 participants who completed at leafter dose 2, data collected November 16, 2022 – January 29, 2023
Adverse Events in persons <18 years 
Single-patient emergency Investigational New 

(EIND) procedures CDC facilitated JYNNEOS EIND authorizations from FDA for 65 pe

years prior to the EUA being issued on August 9, 2022

– CDC solicited information from vaccine providers about adve

occurring during the 28 days after each dose

 Ages: 4 months to 17 years Sex: 58% male Adverse events reported:

– Dose 1: 10 (18%) of 57– Dose 2: 5 (21%) of 24– Injection site reactions: pain, erythema, swelling, and indura– Systemic adverse events: fever, fatigue, and headach

e

 No serious adverse events were reported
VAERS: reports for persons aged <18 years

 JYNNEOS vaccine was administered to 1,245 persons aged <1

U.S during this surveillance period

 VAERS received 25 reports for persons aged <18 years

– Ages from 12 through 17 years– Vaccine administration errors, n = 21 (84%)

• e.g., administered intradermal dose instead of subcu

– Only 1 adverse health event reported: syncope– No serious adverse events reported
Conclusions
Conclusions

 JYNNEOS post-licensure and post-authorization vaccine safet

findings to date are consistent with those observed in clinica

 No new or unexpected safety concerns have been identified Serious adverse events were rare among adults, and none ha

identified among persons aged <18 years

 VAERS and Vaccine Safety Datalink data do not suggest an inc

myocarditis or pericarditis following JYNNEOS, but the possibrisk cannot be excluded
For more information, contact CDC

1-800-CDC-INFO (232-4636)TTY: 1-888-232-6348 www.cdc.govThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.