Document text
National Center for Emergin g and Zoonotic Infectious Diseases
JYNNEOS Vaccine Safety Monitoring During the 2022
Mpox Outbreak ─ United States
Jonathan Duffy, MD, MPH
Immunization Safety Office Centers for Disease Control and Prevention
Advisory Committee on Immunization Practices
February 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) procedures
VAERS
VAERS is the nation’s early warning system for vaccine
safety
JYNNEOS EUA* required reporting to VAERS for
adverse events and vaccine administration errors
The vaccination provider is responsible for MANDATORY reporting of the
following listed events following JYNNEOS to VAERS:
– Vaccine administration errors whether or not associated with an adverse event
– Serious adverse events (irrespective of attribution to vaccination)
– Cases of cardiac events including myocarditis and pericarditis
– Cases of thromboembolic events and neurovascular events
*EUA indications: intradermal injection for individuals aged ≥18 and subcutaneous injection for individuals aged <18 years; Fact Sheet
for Healthcare Providers Administering Vaccine: Emergency Use Authorization of Jynneos (Smallpox and Monkeypox
Vaccine, Live, Non-Replicating) for Prevention of Monkeypox Disease in Individuals Determined to be at High Risk for 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 number of
VAERS reports by the number of vaccine doses administered in the U.S.
– Vaccine doses administered during May 22–January 13 and reported to CDC by January 23, 2023
• Dose 1: 698,188
• Dose 2: 426,980
• Total: 1,125,168
VAERS: JYNNEOS report characteristics, n = 1,817
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 n (%)
Dose in series
1 1,013 (56)
2 471 (26)
Not reported 333 (18)
Route of administration
Intradermal 1,001 (55)
Subcutaneous 378 (21)
Intramuscular 211 (12)
Not reported 227 (12)
VAERS: vaccine administration error reports
Represent 50% of all JYNNEOS VAERS reports
– Of these, 96% did not report an adverse health event
Error reporting rate
– Intradermal: 937 per million doses administered
– Subcutaneous: 306 per million doses administered
Errors frequently reported with attempted intradermal administration:
– Absence of a wheal without vaccine leakage (42%)
– Vaccine leakage from injection site (12%)
rate
All adverse health events VAERS: adverse health event reporting rates per
million doses administered by route of administration
Intradermal rate
All adverse health events 685
Injection site erythema 152 Dizziness 129
Injection site swelling 112
Urticaria 110
Injection site pruritus 93
Erythema 78
Syncope 73
Pruritus 72
Hyperhidrosis 70
Loss of consciousness 69 Injec tion sit e erythema
Injection site swelling
Injection site pain Pain 107
107
99 96
Fatigue Erythema Headache 80 77 77
Dizziness 74
Injection site pruritus Pyrexia 66 66 Subcutaneous
639
Serious Adverse Event definition
Death
A life-threatening adverse event
Inpatient hospitalization or prolongation of existing hospitalization
A persistent or significant incapacity or substantial disruption of the ability
to conduct normal life functions
A congenital anomaly/birth defect
An important medical event that based on appropriate medical judgement
may jeopardize the individual and may require medical or surgical
intervention to prevent one of the outcomes listed above
VAERS: serious adverse events reported after JYNNEOS*,
n = 26
SAE reporting rate: 22 reports per million doses administered
Dehydration Myocarditis (n =5)
Death (n=2)** Idiopathic thrombocytopenic
pur
pura Pericarditi s (n=2)
In
jection site discoloration Urticari a (n=2)
In
jection site pain Appendicitis
Injection site scar Asepti c meningitis
Met
hemoglobinemia Asthenia
Retrograde amnesia Atrial fibrillation
Rha
bdomyolysis Cellulitis
Sudden hearing loss Chest pain
*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 primary
vaccination or revaccination with live vaccinia virus smallpox vaccines
– The mechanism is poorly understood, and it was unknown whether persons who receive JYNNEOS might experience myocarditis or pericarditis
Epidemiologic analysis groupings:
– Myocarditis with or without pericarditis
– Pericarditis
Surveillance risk interval: symptom onset within 30 days after vaccination
Case definitions available at: DOI: 10.15585/mmwr.mm7027e2
Myocarditis rate per million persons during 30-day period
Observed after JYNNEOS
Data source Dose 1
cases doses rate per million
(95% CI) Dose 2
cases doses rate per million
(95% CI)
VAERS 2 726,851 2.75 (0.33–9.94) 3 445,019 6.74 (1.39–19.70)
Vaccine Safety
Datalink 1 37,646 27 (0.67–148) 1 21,919 46 (1.15–254)
Expected
Historical myocarditis population background rates per million persons:
– U.S. military in 20021: 21.6
– MarketScan database, males 18–64 yrs in 2017–20192: 2.7 – 7.5
Historical myocarditis rates after live, replicating smallpox vaccines (Dryvax or ACAM2000) ranged from 78 to 5,230 cases per million persons
1,3
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 period
Observed after JYNNEOS
Data source Dose 1
cases doses rate per million
(95% CI) Dose 2
cases doses rate per million
(95% CI)
VAERS 4 726,851 5.50 (1.50–14) 2 445,019 4.49 (0.54–16.23)
Vaccine Safety
Datalink 0 37,646 0 0 21,919 0
Expected
Historical pericarditis population background rates per million persons:
– Italy, 2001–20051: 22.8
– U.S. Nationwide Inpatient Sample database, 2003–20122: 4.7
Historical pericarditis rate after live, replicating smallpox vaccines (Dryvax
or ACAM2000) was 925 cases per million persons in one U.S. military study3
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 monitoring
Smartphone-based system that uses text messaging to initiate web-based
survey monitoring for adverse events following vaccination
V-safe is used to:
– Characterize the basic safety profile of a vaccine when given outside a clinical trial setting
– Provide information for public health communication around vaccine safety
– Facilitate reporting to the Vaccine Adverse Event Reporting System (VAERS)
for medically attended adverse events following vaccination
V-safe supplements CDC’s other vaccine safety monitoring systems, VAERS and
Vaccine Safety Datalink (VSD)
V-safe Mpox: characteristics of active participants*
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 N=181
n (%)
Race/Ethnicity
White, non-Hispanic 111 (61.3)
Hispanic 28 (15.5)
Asian, non-Hispanic 11 (6.1)
Black, non-Hispanic 10 (5.5)
Multiracial, non-Hispanic 10 (5.5)
Other race, non-Hispanic 2 (1.1)
Unknown race or ethnicity 9 (5.0)
*active participants defined as having completed at least one
survey, November 16, 2022 – January 29, 2023 **defined as self-report of immunocompromising condition or taking immunosuppressive medications at the time of vaccination
V-safe Mpox: reactions and health impact events reported by v-safe
participants at least once in days 0-7 after vaccination, by dose
100
90
81
62
26
19
14
5 80
54
16 14
10
0
0 10 20 30 40 50 60 70 80 Percentage
Any injection site reaction Any systemic reaction Any health impact Unable to perform normal Unable to work or attend Sought medical care (clinic
daily activities school only)
Dose 1 Dose 2
Includes 42 participants who completed at least one survey after dose 1 and 50 participants who completed at least one survey
after dose 2, data collected November 16, 2022 – January 29, 2023
V-safe Mpox: top injection site and systemic reactions reported by v-safe
participants at least once in days 0-7 after Mpox vaccination, by dose
100
90
80 70
6462
60 50
40
30 20 10
0
Redness at site Itching at site Lump at site Swelling at site Fatigue Headache Pain at site Myalgia Rash at site Fever 55 52 50
40
24 24 24
17 17 54
46
40 42
28 26
22
16
6
Dose 1 Dose 2
Includes 42 participants who completed at least one survey after dose 1 and 50 participants who completed at least one survey
after dose 2, data collected November 16, 2022 – January 29, 2023 Percentage
Adverse Events in persons <18 years of age
Single-patient emergency Investigational New Drug
(EIND) procedures
CDC facilitate d JYNNEOS EIND authorization s fro m FDA fo r 65 person s aged <1 8
year s prior to the EUA being issue d o n August 9, 2022
– CDC solicite d informatio n fro m vaccine provider s about adverse event s
occurring durin g the 28 day s afte r each dose
Ages: 4 months to 17 years
Sex: 58% male
Adverse events reported:
– D
ose 1: 10 (18%) of 57
– Dose 2: 5 (21%) of 24
– Injection site reactions: pain, erythema, swelling, and induration
– Systemic adverse events: fever, fatigue, and headache
No serious adverse events were reported
VAERS: reports for persons aged <18 years
JYNNEOS vaccine was administered to 1,245 persons aged <18 years in the
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 subcutaneous dose
– Only 1 adverse health event reported: syncope
– No serious adverse events reported
Conclusions
Conclusions
JYNNEOS post-licensure and post-authorization vaccine safety surveillance
findings to date are consistent with those observed in clinical trials
No new or unexpected safety concerns have been identified
Serious adverse events were rare among adults, and none have been identified among persons aged <18 years
VAERS and Vaccine Safety Datalink data do not suggest an increased risk for myocarditis or pericarditis following JYNNEOS, but the possibility of a small risk cannot be excluded
For more information, contact CDC
1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov
The 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.