Effectiveness of a single-dose Modified Vaccinia Ankara in Human Monkeypox: an observational study

Abstract Background The recent global outbreak of the human monkeypox virus (MPXV) was declared a public health emergency by the World Health Organization. Modified Vaccinia Ankara (MVA) is currently the only FDA-approved vaccine against MPXV that was approved for this indication based on a study in non-human primates. Since there is currently scarce evidence of the efficacy in humans, our objective was to evaluate real-life vaccine effectiveness (VE) after providing one vaccine dose to individuals at risk of MPVX infection. Methods The study cohort included all Clalit Health Services (CHS) members eligible for the MVA vaccine as defined by the Israeli Ministry of Health. The study commenced on July 31, 2022, when the MVA vaccination campaign was initiated in CHS, and participants were followed until September 12, 2022. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association between vaccination and MPXV infections with adjustment for sociodemographic and clinical risk factors. Findings A total of 1,970 subjects met the study eligibility criteria (0.04% of CHS members). Of them, 873 (44%) were vaccinated with MVA and completed at least 25 days of follow-up. 18 infections were confirmed in CHS during the study period, 3 in vaccinated and 15 in unvaccinated status (40.0 versus 6.4 per 100,000 person days). VE was estimated at 79% (95% CI: 24%-94%). Interpretation Our results suggest that a single dose of MVA is associated with a significantly lower risk for MPVX infection in high-risk individuals. These findings highlight that urgent MVA vaccination of high-risk individuals may contribute to the containment of the current MPXV outbreak.