Effectiveness of Modified Vaccinia Ankara-Bavaria Nordic Vaccination in a Population at High Risk of Mpox: A Spanish Cohort Study

Background: With over 7,500 cases notified since April 2022, Spain has experienced the highest incidence of mpox in Europe. From July 12th onwards, the Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) smallpox vaccine was offered as pre-exposure prophylaxis for individuals at high-risk of mpox, including those receiving pre-exposure prophylaxis for HIV (HIV-PrEP). Our aim was to assess the effectiveness of one dose of MVA-BN vaccine as pre-exposure against mpox virus (MPXV) infection in persons on HIV-PrEP. Methods: We conducted a national retrospective cohort study between July 12 and December 12, 2022. Individuals ≥18 years, receiving HIV-PrEP as of July 12 and with no previous MPXV infection or vaccination were eligible. Each day, we matched individuals receiving a first dose of MVA-BN vaccine and unvaccinated controls of the same age group and region. We used a Kaplan-Meier estimator and calculate risk ratios (RR) and vaccine effectiveness (VE = 1-RR). Results: We 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. 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) post-vaccination. Conclusions: One dose of MVA-BN vaccine offered protection against mpox in a most-at-risk population shortly after the vaccination. Further studies need to assess the VE of a second dose and the duration of protection over time.S