Estimated Effectiveness of JYNNEOS Vaccine in Preventing Mpox: A Multijurisdictional Case-Control Study — United States, August 19, 2022–March 31, 2023

As of March 31, 2023, more than 30,000 monkeypox (mpox) cases had been reported in the United States in an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and transgender persons (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) was approved by the Food and Drug Administration (FDA) in 2019 for the prevention of smallpox and mpox via subcutaneous injection as a 2-dose series (0.5 mL per dose, administered 4 weeks apart) (2). To expand vaccine access, an Emergency Use Authorization was issued by FDA on August 9, 2022, for dose-sparing intradermal injection of JYNNEOS as a 2-dose series (0.1 mL per dose, administered 4 weeks apart) (3). Vaccination was available to persons with known or presumed exposure to a person with mpox (postexposure prophylaxis [PEP]), as well as persons at increased risk for mpox or who might benefit from vaccination (preexposure mpox prophylaxis [PrEP]) (4). Because information on JYNNEOS vaccine effectiveness (VE) is limited, a matched case-control study was conducted in 12 U.S. jurisdictions,^† including nine Emerging Infections Program sites and three Epidemiology and Laboratory Capacity sites,^§ to evaluate VE against mpox among MSM and transgender adults aged 18–49 years. During August 19, 2022–March 31, 2023, a total of 309 case-patients were matched to 608 control patients. Adjusted VE was 75.2% (95% CI = 61.2% to 84.2%) for partial vaccination (1 dose) and 85.9% (95% CI = 73.8% to 92.4%) for full vaccination (2 doses). Adjusted VE for full vaccination by subcutaneous, intradermal, and heterologous routes of administration was 88.9% (95% CI = 56.0% to 97.2%), 80.3% (95% CI = 22.9% to 95.0%), and 86.9% (95% CI = 69.1% to 94.5%), respectively. Adjusted VE for full vaccination among immunocompromised participants was 70.2% (95% CI = −37.9% to 93.6%) and among immunocompetent participants was 87.8% (95% CI = 57.5% to 96.5%). JYNNEOS is effective at reducing the risk for mpox. Because duration of protection of 1 versus 2 doses remains unknown, persons at increased risk for mpox exposure should receive the 2-dose series as recommended by the Advisory Committee on Immunization Practices (ACIP),^¶ regardless of administration route or immunocompromise status.

A matched case-control study was conducted in 12 U.S. jurisdictions. Case-patients had a confirmed or probable Monkeypox virus or Orthopoxvirus diagnosis on or after August 19, 2022; they were identified or verified through jurisdiction health departments’ case registries. Control patients had visited a sexual health, HIV care, or HIV PrEP clinic on or after August 19, 2022, and did not receive an mpox diagnosis; they were identified through active and passive recruitment approaches at local clinics in each jurisdiction.** Participation was restricted to sexually active^†† persons aged 18–49 years who self-identified as MSM or transgender. Eligible participants were invited to complete a survey administered online or by telephone in English or Spanish. The survey included questions about demographic characteristics, mpox vaccination, mpox diagnosis, immunocompromising conditions, and exposure history anchored to an index date, defined as date of positive test result (case-patients) or clinic visit (control patients). Survey responses were recorded in REDCap (version 13.1.26; Vanderbilt University). Participants’ vaccination status was verified using state vaccination registries, where available. Participants were categorized as fully vaccinated, partially vaccinated, or unvaccinated based on the number of JYNNEOS doses they received relative to their index date.^§§

Each case-patient was matched with up to four control patients based on state or region^¶¶ and index date (within 4 weeks). Conditional logistic regression models were used to estimate crude and adjusted odds ratios evaluating the association between vaccination status and case- or control patient status. The adjusted model accounted for covariates identified a priori, including age, race and ethnicity, immunocompromising conditions,*** and close contact with a person with known mpox.^††† VE was calculated as (1 – odds ratio) x 100%. VE estimates were stratified a priori by immunocompromise status and route of vaccine administration (subcutaneous, intradermal, or heterologous [i.e., a different route for each dose]). Analyses were conducted using the survival package in R statistical software (version 4.2.2; The R Foundation). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.^§§§

Among 1,414 respondents, 1,127 (86.1%) met the minimum data element requirements^¶¶¶ for inclusion in the analysis, and 309 (89.6%) of 345 case-patients and 608 (77.7%) of 782 control patients were matched. A larger proportion of case- than control patients identified as non-Hispanic Black or African American (27.2% versus 16.9%) or Hispanic or Latino (32.4% versus 23.4%) (Table 1). Larger proportions of case- than control patients reported experiencing recent homelessness (7.9% versus 2.7%), engaging in transactional sex (9.1% versus 3.3%), and living with HIV (48.1% versus 24.0%); among participants who did not report living with HIV, a smaller proportion of case- than control patients reported using HIV PrEP (54.4% versus 66.8%). Larger proportions of case- than control patients were classified as immunocompromised (46.6% versus 26.0%) and reported recent close contact with a known mpox case (23.0% versus 3.9%).

Among the 917 participants included in the VE analysis, 206 (22.5%) were fully vaccinated, 295 (32.2%) were partially vaccinated, and 416 (45.4%) were unvaccinated. Unadjusted VE was 75.7% for partial vaccination and 87.4% for full vaccination (Table 2). After adjusting for age, race and ethnicity, immunocompromise status, and close contact with a person with known mpox, VE was 75.2% for partial vaccination and 85.9% for full vaccination. Among partially vaccinated participants, adjusted VE by route of administration was 77.0% for subcutaneous and 80.6% for intradermal administration. Among fully vaccinated participants, adjusted VE was 88.9% for subcutaneous, 80.3% for intradermal, and 86.9% for heterologous administration. Among participants with an immunocompromising condition, adjusted VE was 51.0% for partial vaccination and 70.2% for full vaccination, both with negative lower 95% CI bounds. Among participants without an immunocompromising condition, adjusted VE was 72.1% for partial vaccination and 87.8% for full vaccination.

Acknowledgments

Susan Fuller, Rainy Henry, Angelica O’Connor, Alvin Shultz, Jason Snow, CDC; Kimberly Gonzalez Barrera, Samuel Holland, California Department of Public Health; Ryan Buckman, Maria Rosales, California Emerging Infections Program; Jennifer House, Colorado Department of Health and Environment; Eric D. Anthony, Mary Frances De Rose, Sarah Gillani, DC Health; Jason Beverley, Division of STD and TB Control, DC Health; Nadine Oosmanally, Melissa Tobin-D’Angelo, Georgia Department of Public Health; Victoria Baldwin-Lawson, Nathaniel Elijah Barrera-Nitz, Sarah C. Busby, Rachael Gill, Erica Hazra, Maryam Heydari, Katherine A. Lee, Molly McAlvany, Taelor Moran, Emily Nelson, Bianca Perez, Gennesis Quinonez, Sofia Santoro, Paola Santos, Stepy Thomas, Emma Grace Turner, Georgia Emerging Infections Program; Hennepin County Public Health – Red Door Clinic; Sharon Balter, Chelsea Foo, Meredith Haddix, Andrea Kim, Moon Kim, Tae Hee Koo, Sonali Kulkarni, Olivia Moir, Kathleen Poortinga, Nava Yeganeh, Sherry Yin, Los Angeles County Department of Public Health; David Crum, Heather Rutz, Pat Ryan, Sophia Wozny, Maryland Department of Health; Marcie Babcock, Taylor Campbell, Beth Cleary, Paige D’Heilly, Andrew Frederick, Jayne Griffith, Cynthia Kenyon, Miriam Muscoplat, Ali Ruprecht, Minnesota Department of Health; Anthony M. Mills, Men’s Health Foundation; Meaghan Abrego, Bryon Backenson, Youjung Byun, Charlotte DelBarba, New York State Department of Health; Prachi Dahl, Kelly Jamison, Ciarra Leocadio, New York City Department of Health and Mental Hygiene; Josh Arevalo, Public Health Division, Multnomah Health Department; Greg Chambers, Jacqueline Logan, Tennessee Department of Health; Shealynn Hilliard, Jacob Scutaru, Trillium Health; Kristin E. Smith, University of Rochester Medical Center; Arthur L. Reingold, University of California, Berkeley; Pepper J. Heifner, Kristin Rager, Shertise Stogner, Del Ray Zimmerman, Vanderbilt Medical Center.

Corresponding author: Alexandra F. Dalton, adalton@cdc.gov.

¹CDC Mpox Emergency Response Team; ²California Emerging Infections Program; ³Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee; ⁴New York City Department of Health and Mental Hygiene, New York, New York; ⁵DC Health, Washington, DC; ⁶Public Health Division, Oregon Health Authority; ⁷Maryland Department of Health; ⁸University of Rochester School of Medicine and Dentistry, Rochester, New York; ⁹Georgia Emerging Infections Program, Georgia Department of Health; ¹⁰Emory University School of Medicine, Atlanta, Georgia; ¹¹Minnesota Department of Health; ¹²The Connecticut Emerging Infections Program, Yale School of Public Health, New Haven, Connecticut; ¹³New York State Department of Health; ¹⁴Career Epidemiology Field Officer Program, CDC; ¹⁵Los Angeles County Department of Public Health, Los Angeles, California; ¹⁶Colorado Department of Health and Environment; ¹⁷Denver Health, Denver, Colorado; ¹⁸Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

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Abbreviations: PrEP = preexposure prophylaxis; STI = sexually transmitted infection.
* Case-patients and control patients were recruited from the following 12 U.S. jurisdictions: California (excluding Los Angeles County), Colorado, Connecticut, Georgia, District of Columbia, Los Angeles County, Maryland, Minnesota, New York (excluding New York City), New York City, Oregon, and Tennessee.
^† Case-patients were identified or verified by jurisdiction health departments and had a confirmed or probable Monkeypox virus or Orthopoxvirus diagnosis on or after August 19, 2022.
^§ Control patients visited an STI, HIV care, or HIV PrEP clinic on or after August 19, 2022.
^¶ Numbers might not sum to case- or control patient totals due to missing data. Percentages were calculated using nonmissing data.
** P-values comparing the percentage of case-patients to control patients by sociodemographic and health categories were calculated using Pearson’s chi-square test. P-values for continuous variables were calculated using the Kruskal-Wallis test.
^†† Participants reporting Hispanic ethnicity were categorized as Hispanic or Latino and might be of any race. The Other race category includes Asian, Native Hawaiian or other Pacific Islander, and American Indian or Alaska Native persons.
^§§ Transactional sex was defined as a respondent’s affirmative response when asked whether someone gave them money, drugs, or other resources (e.g., housing) in exchange for sex during the 3 weeks before completing the survey.
^¶¶ HIV PrEP use was calculated among persons who did not report living with HIV.
*** Immunocompromising conditions were based on self-report and defined as living with HIV, having a medical condition that weakens the immune response, or taking a medicine that weakens the immune response.
^††† Close contact with an mpox case-patient was defined as intimate or nonintimate contact, including sex, hugging, kissing, sharing food or utensils, sharing sheets or towels, or sharing a living space, during the 3 weeks preceding the onset of mpox signs and symptoms.
^§§§ Participants were asked to report the number of sexual partners they had during the 3 weeks before completing the survey.
^¶¶¶ Participants were asked to report STI diagnoses during the 3 weeks before completing the survey.
**** Participants were categorized as unvaccinated if no reported doses were received on or before the index date. Participants were categorized as partially vaccinated if they received 1 dose ≥14 days before the index date and fully vaccinated if they received 2 doses ≥24 days apart (to allow for a 4-day window) and the second dose was received ≥14 days before the index date. Participants who received their first vaccine dose ≤13 days before their index date were excluded. When vaccination status as recorded in state vaccination registries was unavailable, participant-recorded vaccination status was used.
^†††† Index event was defined as the date of positive test result for case-patients or clinic visit for control patients.

Abbreviation: VE = vaccine effectiveness.
* Numbers in subanalyses might not sum to case- or control patient totals from the overall analysis because matched case-control pairs might have differed by route of administration or immunocompromise status and were therefore excluded when restricted to these populations.
^† Overall models and models by administration route were adjusted for age, race and ethnicity, immunocompromising conditions, and close contact with a person with known mpox. Models by immunocompromise status were adjusted for age, race and ethnicity, and close contact with a person with known mpox.
^§ Participants were categorized as fully vaccinated if they received 2 doses ≥24 days apart (to allow for a 4-day window), and the second dose was received ≥14 days before the index date.
^¶ Participants were categorized as partially vaccinated if they received 1 dose ≥14 days before the index date.
** Immunocompromising conditions were based on self-report and defined as living with HIV, having a medical condition that weakens the immune response, or taking a medicine that weakens the immune response.