Abstract and Introduction
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. 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). 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). 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]). 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.
Morbidity and Mortality Weekly Report. 2023;72(20):553-558. © 2023 Centers for Disease Control and Prevention (CDC)