Effectiveness and Safety of the MVA-BN vaccine against Mpox in at-risk individuals in the United States (USMVAc)

Background: In July 2022, the WHO declared the mpox outbreak a public health emergency of international concern. In August, the Modified Vaccinia Ankara Bavarian Nordic (MVA-BN) vaccine was granted emergency use authorization in the United States (US) for at-risk individuals, namely, men who have sex with men (MSM) and transgender women who had been disproportionately affected. This triggered the need to generate real-world vaccine effectiveness and safety evidence in this population.

Objectives: To evaluate the effectiveness and safety of the MVA-BN vaccine for prevention of mpox in a cohort of MSM and transgender women.

Methods: This retrospective, observational cohort study using HealthVerity administrative US healthcare data (EUPAS104386) is part of a larger program with two additional, complementary, prospective and retrospective studies (SEMVAc, TEMVAc EUPAS50093). For the assessment of vaccine effectiveness, subjects with full MVA-BN vaccination (2 doses ≥28 days apart; index date assigned 14 days after the second dose) between August and September 2022 were matched to 5 unvaccinated subjects on calendar date, age, US region, and insurance type. Standardized mortality ratio weighting (SMR) was used to control for measured confounding. Subjects were followed from index date (14 days after the second dose or matched date) until disenrollment, death, or end of study period. Two sensitivity analysis cohorts compared all subjects who received any MVA-BN dose and single dose, respectively, to matched unvaccinated subjects. To evaluate vaccine safety, adverse events of special interest (pericarditis, myocarditis, encephalitis, and anaphylaxis) were assessed among the any dose cohort. Analyses were performed using Aetion Substantiate and R.

Results: There were 163 fully vaccinated subjects initially matched to 815 unvaccinated comparator subjects. After subsequent SMR weighting, compared to a weighted pseudo-population of 159.85 (effective sample size of 303) in the unvaccinated comparator group, full vaccination with MVA-BN demonstrated 89% effectiveness (95% CI: 12% - 99%) against mpox disease. Vaccine effectiveness was 64% (95% CI: 40 - 78%) among those with any dose and 70% (95% CI: 44 - 84%) among those with a single dose. The vaccine showed a favorable safety profile, with only one observed pericarditis event in the 28-day risk window post-vaccination.

Conclusions: These data contribute to the totality of evidence supporting the benefit/risk profile of the MVA-BN vaccine to prevent mpox in MSM and transgender women, with full vaccination showing improved protection as compared to 1 dose only. Results from this study will be supplemented by forthcoming results from the SEMVAc and TEMVAc studies.