Both Smallpox and Mpox Vaccine Reduce Mpox Disease Severity and Symptoms

Abstract Background Data on the impact of completing 2 doses of the modified vaccinia Ankara vaccine and/or smallpox vaccination in childhood on Mpox disease severity remain limited. During the last months of 2024, Germany faced a second Mpox wave, providing the opportunity to study the impact of different vaccine regimens including smallpox vaccination. Methods Retrospective analysis of all cases diagnosed at 17 participating German centers 2022–2024. Cases were grouped according to smallpox vaccine history: “unvaccinated,” “incomplete” (vaccinations only during childhood and/or only one MVA BN), “complete” (2 MVA BN 1 month prior to Mpox diagnosis). Disease severity was assessed by a 7-item Mpox Severity Scoring System (MPOX-SSS). Results Of 273 Mpox infections, 42% occurred in men who have sex with men (MSM) living with HIV (median CD4 724 cells/µl, 91% 50 HIV-RNA copies/ml), 58% occurred in MSM without HIV, most of them using HIV PrEP. Median age was 38 years (IQR 30–44). Vaccinated individuals demonstrated lower MPOX-SSS scores compared to unvaccinated individuals (mean score 5.46 vs 7.15, P .001). Vaccinated individuals also had less fever (23% vs 59%, P .001), headaches/chills (29% vs 54%, P .001), and swollen lymph nodes (38% vs 56%, P = .02). Conclusions Both incomplete and complete vaccine courses including smallpox vaccination during childhood appear to reduce Mpox disease severity and symptoms. In settings of limited vaccine resources, unvaccinated risk groups should be prioritized.