Effectiveness of one dose of MVA-BN smallpox vaccine against monkeypox in England using the case-coverage method

Background Like many other countries worldwide, the UK experienced a national outbreak of monkeypox disease in May 2022, with case numbers rising rapidly, mainly among gay, bisexual and other men who have sex with men (GBMSM). To control the outbreak, Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN), an attenuated smallpox vaccine, was offered to high-risk GBMSM. We assessed the effectiveness of a single MVA-BN dose against monkeypox disease in high-risk GBMSM. Methods Monkeypox cases in England were sent questionnaires collecting information on demographics, vaccination history and symptoms. Returned questionnaires with a rash onset date (or alternative proxy) between July 04 and October 09, 2022 were included. Females, heterosexual men, and those with missing vaccination information were excluded. Vaccine effectiveness was calculated using the case-coverage method where vaccine coverage among cases is compared to coverage in the eligible population, estimated from doses given to GBMSM and the estimated size of high-risk GBMSM. Sensitivity analysis included +/-20% differences in estimated high-risk GBMSM population size. Findings Vaccine uptake among eligible GBMSM increased steadily from July 2022, reaching 47% by October 09, 2022. Of the 363 confirmed cases, 8 occurred [≥]14 days after vaccination, 32 within 0-13 days after vaccination, and the rest were unvaccinated. The estimated vaccine effectiveness at least 14 days after a single dose was 78% (95% CI: 54%-89%), with a range of +/-7% in sensitivity analyses. Vaccine effectiveness within 0 to 13 days after vaccination was -4% (95% CI: -50% to 29%). Interpretation A single MVA-BN dose was highly protective against monkeypox disease among high-risk GBMSM.