Reduction in the risk of mpox infection after MVA-BN vaccination in individuals on HIV pre-exposure prophylaxis: a Spanish cohort study

ObjectivesTo assess the effectiveness of at least one-dose of the Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) smallpox vaccine, administered pre-exposure, against mpox virus (MPXV) infection in persons receiving pre-exposure prophylaxis for HIV (HIV-PrEP). DesignRetrospective cohort, constructed by deterministic linkage of electronic health records. Setting15 of 19 regions in Spain (>95% population), between July 12 and December 12, 2022 ParticipantsMen [≥]18 years, receiving HIV-PrEP as of July 12 and with no previous MPXV infection or vaccination against mpox. InterventionsOn each day, we matched individuals receiving a first dose of MVA-BN vaccine pre-exposure and unvaccinated controls of the same age ({+/-}5 years) and region. Main outcome measuresWe estimated the risk of laboratory-confirmed infection with MPXV using a Kaplan-Meier estimator and calculated risk ratios (RR) and vaccine effectiveness (VE=1-RR). ResultsWe included 5,660 matched pairs, with a median follow-up of 62 days (interquartile range 24-97). Mpox cumulative incidence was 5.6 per 1,000 (25 cases) in unvaccinated and 3.5 per 1,000 (18 cases) in vaccinated; last case occurred at 63 and 17 days after enrolment, respectively. No effect was found during days 0-6 post-vaccination (VE -38.3; 95% confidence interval (95%CI): -332.7; 46.4), but VE was 65% in [≥]7 days (95%CI 22.9; 88.0) and 79% in [≥]14 days (95%CI 33.3; 100.0) after vaccination. ConclusionAt least one dose of MVA-BN vaccine offered protection against mpox in a most-at-risk population. Because the incidence of mpox was decreasing shortly after the vaccination campaign began, we can only assess its effectiveness shortly after vaccination. Further studies need to assess the VE of a second dose and the duration of protection over time. O_LIWhat is already known on this topic: O_LIMVA-BN vaccination is effective in producing an immune response against mpox virus (MPXV) and has shown clinical efficacy in animal models. C_LIO_LIDuring the current mpox outbreak, observational studies have indicated that MVA-BN vaccines are effective in preventing MPXV infection in real-life. C_LIO_LINo individual-based cohort study with proper implementation of causal inference methods, providing the highest quality of evidence with observational data, has been published to date. C_LI C_LIO_LIWhat this study adds: O_LIThe administration of one dose of MVA-BN vaccine in a high-risk population (men receiving HIV pre-exposure prophylaxis) reduced the risk of MPXV infection by 65% starting 7 days after the administration and by 79% starting 14 days after. C_LIO_LIEffectiveness of MVA-BN vaccine was similar in population under 50 years, a group where childhood smallpox vaccination is rare in Spain. C_LIO_LIThis is the first study to estimate MVA-BN vaccine effectiveness in one of the countries most affected by the mpox outbreak in 2022, with a design and methods providing high quality evidence. C_LI C_LI