National Center for Emerging and Zoonotic Infectious Diseases

JYNNEOS Vaccine Effectiveness 

Anna Chard, PhD, MPHLT, US Public Health Service

Advisory Committee on Immunization PracticesFebruary 22, 2023

Vaccine Effectiveness TeamVaccine Task Force2022 Multinational Mpox Outbreak ResponseCenters for Disease Control and Prevention
Background

 Efficacy of JYNNEOS against mpox has been inferred from an

immunogenicity studies, but has never been demonstrated 

 No real-world vaccine effectiveness (VE) estimates for JYNN

mpox disease prior to current multinational outbreak

 Key questions:

1. What is the effectiveness of JYNNEOS vaccine against mpox diseas

a) What is VE of partial (1 dose) versus full (2 doses) vaccination?

2. Are there differences in VE by route of vaccine administration?3. Are there differences in VE among persons with immunocomprom4. What is the duration of protection conferred from JYNNEOS vaccin
Organization of presentation 

 Vaccine performance

 Incidence of mpox among unvaccinated persons versus persons receiv

dose in the United States (U.S)

 Vaccine effectiveness (VE) of JYNNEOS given as post-exposur

(PEP) against mpox disease, New York City

 VE of JYNNEOS given as pre-exposure prophylaxis (PrEP) ag

disease

1. Israel single dose VE Study: Real-world effectiveness of a single dose 

in males

2. EPIC Cosmos Case-Control Study: VE of 1 and 2 doses against mpox d3. Multi-jurisdictional Case-Control Study: Interim estimate of VE of 2 d

mpox disease in 12 U.S. jurisdictions

4. New York State Case-Control Study: Preliminary estimates of VE of 1 

against mpox disease 
Vaccine performance
Weekly mpox incidence by vaccination status: M

 Data sources: Mpox case data, vaccine administration data, es

vaccine eligible population*

 Design: Comparison of mpox incidence among persons who w

unvaccinated and those who had received either 1 or 2 JYNNEO

 Population: 9,544 reported mpox cases among men aged 18–4

43 U.S. jurisdictions

 Time period: July 31–October 1, 2022 Analysis: 

 Estimated weekly mpox incidence for persons with partial (1 dose) and 

vaccination and persons eligible but unvaccinated

 Calculated incidence rate ratio using negative binomial regression

*Estimated population per jurisdiction of men who have sex with men (MSM) who are living with HIV or MSM who exposure prophylaxis.Source: Payne AB, et al. Reduced Risk for Mpox After Receipt of 1 or 2 Doses of JYNNEOS Vaccine Compared with Persons — 43 U.S. Jurisdictions, July 31–October 1, 2022. MMWR Morb Mortal Wkly Rep 2022;71:1560–1564. 
Weekly mpox incidence,* by vaccination status among males ag

eligible for vaccination§

0

50

100150200250300350

31-Jul-22

2-Aug-22

4-Aug-22

6-Aug-22

8-Aug-22

10-Aug-22

12-Aug-22

14-Aug-22

16-Aug-22

18-Aug-22

20-Aug-22

22-Aug-22

24-Aug-22

26-Aug-22

28-Aug-22

30-Aug-22

1-Sep-22

3-Sep-22

5-Sep-22

7-Sep-22

9-Sep-22

11-Sep-22

13-Sep-22

15-Sep-22

17-Sep-22

19-Sep-22

21-Sep-22

23-Sep-22

25-Sep-22

Monkeypox Incidence

Week

UnvaccinatedVaccine dose 1 received ≥ 14 days earlierVaccine dose 2 received ≥ 14 days earlier

* Cases per 100,000 population. Rate in vaccinated persons = number of probable or confirmed cases reported to CDC with date of illness onset, specimen collection, lab test completion, admission, diagnosis, discharge, case inv

reported to the county, state, or public health department (earliest available date) ≥14 days after receiving the first dose or second dose of JYNNEOS vaccine among total vaccinated population as of 2 weeks previously. Rate in u

reported to CDC without evidence of vaccination among total unvaccinated population.§ Gay, bisexual, and other men who have sex with men who have HIV infection or who are eligible to receive HIV preexposure prophylaxis were considered eligible for vaccination.¶ Alabama, Alaska, California, Colorado, Connecticut, District of Columbia, Florida, Georgia, Hawaii, Idaho, Illinois, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, Missour(excluding New York City), North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Puerto Rico, Rhode Island, South Carolina, South Dakota, Tennessee, Utah, Vermont, Virginia, West Virginia, Wisconsin, and Wyoming.** Jurisdictions were included if age and sex assigned at birth or gender identity was available for ≥70% of cases reported, vaccination status was available for ≥50% of cases in males (defined by either sex assigned at birth or ge

cases were linked to immunization registry entries, and de-identified vaccination administration data were submitted to CDC. Source: Payne AB, et al. Reduced Risk for Mpox After Receipt of 1 or 2 Doses of JYNNEOS Vaccine Compared with Risk Among Unvaccinated Persons — 43 U.S. Jurisdictions, July 31–October 1, 2022. 

July 31, 2022 – October 1, 2022 (43 U.S. jurisdictions**) 

Mpox incidence amoindividuals was 7.4 (9

as high as persons reJYNNEOS vaccine. Mpox incidence amoindividuals was 9.6 (9times as high as persof JYNNEOS vaccine.No difference observperformance betweeintradermal administ
Vaccine effectiveness of JYNNEOS 

administered as PEP against mpox
JYNNEOS effectiveness as PEP against mpox, New Yor

(unpublished data)

 Design: Cohort evaluation of individuals ages >18 years residing in NYC ident

routine Department of Health contact investigations to a case-patient with m22—August 24, 2022 and no vaccination or disease history prior to exposure

 PEP: Receipt of 1st dose of JYNNEOS <14 days of exposure and prior to date o

if applicable

 Case-patient: Exposed individuals who developed symptom onset < 21 days 

(incubation period) with laboratory confirmation

 Analysis: VE of a single dose of JYNNEOS administered subcutaneously <14 d

as PEP for preventing laboratory-confirmed mpox disease as [(1 – Relative Ri

 Results: Among individuals with high-risk* exposure, vaccine effectiveness w

51%-92%) with PEP <14 days after last exposure (n=273) and 79% (46%-94%days after first exposure (n=208)**

*Defined according to the CDC Interim Community Exposure Risk Assessment and Recommendation***Unadjusted; in univariate analyses, race/ethnicity and age-group were not significantly associate
Vaccine effectiveness of JYNNEOS 

administered as PrEP against mpox
Israel single-dose VE study: Methods

 Vaccination: Single, subcutaneous dose of Modified Vaccinia A

Nordic (MVA-BN)

 Design: Retrospective, observational cohort using electronic h

from a single integrated health center in Israel

 Population: 2,054 men eligible* for vaccination  Time period: July 31, 2022 – December 25, 2022 Analysis: 

 VE estimated using Cox proportional hazards regression with vaccinati

time-varying covariate

 Model adjusted for sociodemographic and clinical risk factors

*Males aged 18 – 42 years who were dispensed HIV-PrEP at least for one month since January 1, 2022, or (b) males aged 18 – 42 and also were diagnosed with one or more sexually transmitted infections (STIs) since January 1, 2022.Source: Sagy, Y. W. et al. Real-world effectiveness of a single dose of mpox vaccine in males. Nature Medicine https://doi.org/10.1
Israel single-dose VE study: Results

• 5 mpox cases among vaccinated

individuals

• 16 mpox cases among 

unvaccinated individuals

• Adjusted single-dose vaccine 

effectiveness was 86% (95% CI: 59%-95%)

Source: Sagy, Y. W. et al. Real-world effectiveness of a single dose of mpox vaccine in males. Nature Medicine http

023-02229-3 (2023).
Epic Cosmos Case-Control Study: Methods

 Data Source: Epic’s electronic health record (EHR) platform, Co

includes records from >169 million patients across the U.S.

 Design: Case-control analysis, matched 1:4 based on week of in

HHS region, and gender identity 

 Case patients: Patients with an mpox diagnosis or positive orthopo

virus laboratory result from 8/15 - 11/19/2022

 Control patients: Patients with an incident HIV diagnosis or HIV pre

prophylaxis (PrEP) prescription from 8/15 - 11/19/2022

 Analysis:

 VE estimated using conditional logistic regression Adjusted for age, race/ethnicity, social vulnerability index, immuno

conditions

 Stratified by route of administration and immunocompromised sta
Cases

(n=2,913)

Controls(n=8,319) Adjusted* VE (95% CI)

Overall VE, full vaccination (2 doses) 25 335 66 (47, 78)

No immunocompromising conditions 14 312 76 (58, 87)2 doses administered subcutaneously 6 63 54 (-9, 81)2 doses administered intradermally 5 42 46 (-45, 80)2 doses administered heterologously 8 150 75 (48, 88)

Overall VE, partial vaccination (1 dose) 146 1000 36 (22, 47)

No immunocompromising conditions 102 932 41 (25, 53)1 dose administered subcutaneously 106 704 32 (15, 45)1 dose administered intradermally 27 186 41 (7, 62)

-60 -40 -20 0 2

Vaccine Effec

*Adjusted for age, race/ethnicity, social vulnerability index, and immunocompromising conditions.Cases/controls matched on week of index event, HHS region, gender identity.

Epic Cosmos Case-Control Study: JYNNEOS VE for fulvaccination, August 15-November 19, 2022, United S(unpublished data)
Multi-jurisdictional Case-Control Study: Metho

 Design: Case-control study Population: Men who have sex with men; ages 18-49; 12 U. Methods:

 Cases identified from jurisdictions’ probable and confirme

lists

 Controls identified from healthcare settings providing HIV 

sexually transmitted infection (STI) clinics

 Demographics, exposure history, and vaccination history c

electronic surveys

 Vaccination status confirmed by state immunization regist

 Analysis: Logistic regression with random intercept for jurisd

adjusted for age, race/ethnicity, number of sexual partners, with a confirmed/probable case, and month of index event
Cases

(n=167)

Controls(n=256) Adjusted* VE (95% CI)

Overall VE, full vaccination (2 doses) 14 122 76% (48%-89%)

No immunocompromising conditions 8 61 90% (66%-97%)Immunocompromising conditions

Overall VE, partial vaccination (1 dose)

No immunocompromising conditionsImmunocompromising conditions

0 20 

Multi-jurisdictional Case-Control Study Interim Resul

vaccination (unpublished data)

Not sufficiently powered for interi

*Adjusted for age, race/ethnicity, immunocompromised status, reported close contact with a confirmed/suspected mpox case in 3 weeks prior to index event, and month of index event
New York State Case-Control Study: Preliminary Estim

(unpublished data)

 Data source: Linkage of case surveillance to immunization registr

State, excluding New York City

 Cases: Adult male mpox cases during July 24 – October 31, 2022 Controls: Adult male STI cases (rectal gonorrhea or primary syphi

24 – October 31, 2022

 Analysis: Conditional logistic regression model adjusted for diagn

age, region within state

mpox cases

(n=252)

STI controls

(n=255) V

Unvaccinated 230 (91%) 204 (80%) Partial vaccination 10 (4%) 23 (9%) 68% Full vaccination 2 (1%) 19 (7%) 89% 
Summary
Vaccine effectiveness of JYNNEOS against mpox range

89% for full vaccination and 36%-86% for partial vacc

Cases Controls Adjusted* VE (95% CI)

Full vaccination (2 doses)

Epic Cosmos case-control study 25 335 66% (47%- 78%)Multi-jurisdictional case-control study 14 122 76% (48%-89%)New York State case-control study 2 19 89% (44%-98%)

Partial vaccination (1 dose)

Israel single-dose study 5 16 86% (59%-95%)Epic Cosmos case-control study 146 1000 36% (22%-47%)New York State case-control study 10 23 68% (25%-86%)

0 20 

Vacc
Vaccine effectiveness of JYNNEOS against mpox

 JYNNEOS vaccine is effective at reducing risk of mpox diseas Protection provided by both 1 and 2 doses of JYNNEOS vacc Highest protection provided by 2 doses, regardless of route 

administration

 Further research needed to evaluate whether immunocomp

modulates VE 

 Further research needed to assess duration of protection
Acknowledgements

• Alpha Oumar Diallo• Alexandra Dalton• Amy Fothergill• Leora Feldstein• Nicholas Deputy• Danielle Moulia• Amanda Payne• Tom Shimabukuro• Mo Patel• Adam Cohen• Rosalind Carter• Amanda Cohn• Daniel Payne• Logan Ray• Kristen Kugeler• Michelle Canning• Matthew Cole• Kennedy Houck• Nathaniel Lewis• Jennifer Farrar• Lizzie White• Epic COSMOS Investigators

• Jackie Gerhart• Danessa Sandman• Dave Little• Cory Sweet• Joe Deckert• Eric Barkley• Neil Sandburg

• Investigators from NYC Health

• Jennifer B. Rosen• Robert J. Arciuolo• Preeti Pathela• Jennifer Baumgartner• Julia Latash• Lenka Malec• Ellen H. Lee• Vasudha Reddy• Renee King• Joseph Edward Real• Jane R. Zucker

• Investigators from New York State Health 

Dept

• Eli Rosenberg• Vajeera Dorabawila• Rachel Hart-Malloy• Wilson Miranda• Bridget Anderson• Bryon Backenson• Charlotte DelBarba• Meaghan Abrego• Cori Tice• Claire McGarry• Emily Lutterloh• Michele Boulais• Ethan Mitchell• Charles Gonzalez• Travis O’Donnell• Michael Kharfen• James McDonald• Ursula Bauer

• Multi-jurisdictional case-control study 

investigators:

• Bridget Anderson• Suzanne McGuire• Adam Rowe• Kerianne Engesser

• Jemma Rowlands• Ghinwa Dumyati• Christina Felsen• Erin Licherdell• Kristin Smith• Shealynn Hilliard• Will Still• Allison Morrow• Sarah Gillani• Eric Anthony• Mary Fran DeRose• Jessica Castilho• Mary Margaret Fill• Keipp Talbot• Tiffanie Markus• Danielle Ndi• Kristine Mansilla-Dubon• Bentley Akok• Sweta Tiwari• Caleb Wiedeman• Jacqueline Logan• Greg Chambers• Yelena Tourkina• Kim Toevs• Lynn Rampe• Eric Richardson• Jaxon Mitchell• Josh Arevalo• Melissa Sutton• Paul Cieslak• Sam Hawkins• Amber Britton• Bianca Perez• Erica Hazra• Molly McAlvany• Taelor Moran• Tamsin van der Woude• Katherine Lee• Rachael Gill

• • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • 
1-800-CDC-INFO (232-4636)

TTY: 1-888-232-6348 www.cdc.gov