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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.

BackgroundThe 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.MethodsThe study cohort included all Clalit Health Services (CHS) members estimated to be at moderate to high risk for MPXV infection. The study commenced on July 31, 2022, when the MVA vaccination campaign was initiated in CHS, and participants were followed until August 10, 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.Results8,168 subjects met the study eligibility criteria (0.17% of CHS members). Of them, 626 (7.7%) were vaccinated with MVA and completed at least 7 days of follow-up. 14 infections were confirmed in CHS during the study period, all within the study cohort and all in unvaccinated participants. VE was estimated at 100% (95% CI: 100%-100%).ConclusionsThese short-term preliminary results suggest a very high VE of a single dose of MVA for MPVX infection in moderate to high-risk individuals. These findings suggest that urgent MVA vaccination of high-risk subjects may contribute to outbreak containment.

Background As the current global resurgence of monkeypox virus infection (MPXVi) continues, the immediate supply of vaccines is lower than the demand. Therefore, prioritization of vaccinations for the highest risk subjects using routine medical records is warranted. Methods This population-based cohort study included all Clalit Health Services (CHS) subjects deemed at moderate-to-high risk for MPXVi: males who purchased HIV-PrEP or tested for sexually transmitted infections since January 2021, aged 25–46 who received Human Papilloma Virus vaccine, or HIV-positive. We defined a high-risk group within the cohort and compared the risk for MPXVi to the moderate-risk group from June 6 (the first known CHS case) until Jul 25, 2022. Results Out of 4.8 million CHS members, 8,089 met the study eligibility criteria (0.18%). During the study period, 54 CHS members tested positive for MPXVi, 51 (94%) of whom were included in the study cohort. The highest risk group included 2,274 (28%) subjects who met the following criteria in 2022: Used HIV-PrEP or erectile dysfunction therapy or were diagnosed with STIs by rectal PCR. The hazard ratio for MPXV infection in the high-risk group compared to the moderate-risk group is 19.35 (95% CI: 8.26–45.36). The sensitivity, specificity, NPV, and PPV for MPXV infection are 88.2%, 72.3%, 99.9%, and 2.0%, respectively. Conclusions Subjects in the highest risk group have a nearly 20-fold risk for MPXV infection compared to the moderate risk group. Our findings may assist in prioritizing new vaccines by promptly identifying high-risk populations without the need for intrusive sexual behavior questioning.