Effect of JYNNEOS vaccination on mpox clinical progression among cisgender male cases with confirmed infection

BackgroundThe JYNNEOS modified vaccinia virus Ankara vaccine has proven effective in preventing clade IIb mpox disease during the ongoing global outbreak associated with sexual transmission. However, understanding of the effect of vaccination on mpox clinical presentation remains limited. MethodsWe interviewed cisgender males with confirmed mpox (cases) reported to the California Department of Public Health from May 2022 through December 2023. We ascertained cases vaccination statuses via the California Immunization Registry. We estimated JYNNEOS vaccine effectiveness against progression (VEP) to disease involving disseminated lesions via the adjusted odds ratio of vaccination, comparing cases who reported lesions disseminated across multiple anatomical regions to cases who reported lesions contained to a single anatomical region. We used the same approach to estimate VEP for prodromal symptoms. FindingsAnalyses included 4,613 cases, among whom 3,045 (66.0%) reported disseminated lesions and 1,956 (42.4%) had HIV infection. Among cases who reported disseminated lesions, 114 (3.7%) received pre-exposure vaccination and 43 (1.4%) received post-exposure vaccination only. In contrast, among cases who reported lesions contained to a single anatomical region, 286 (18.2%) received pre-exposure vaccination and 146 (9.3%) received post-exposure vaccination only. For any pre-exposure vaccination, VEP was 58.9% (95% confidence interval: 50.4-65.9%), while VEP for two pre-exposure doses was 61.0% (47.3-71.1%). For post-exposure vaccination, VEP was 15.9% (3.3-26.8%). Among cases without HIV and cases with HIV, pre-exposure VEP was 66.4% (56.6-74.0%) and 45.3% (28.0-58.5%), respectively. Pre-exposure vaccination was also associated with reduced odds for illness involving fever, chills, and lymphadenopathy. InterpretationAmong cisgender males with mpox, pre-exposure vaccination with JYNNEOS is associated with less severe illness. Awareness of an attenuated disease phenotype involving localized lesions without accompanying prodromal symptoms is needed among providers to ensure accurate diagnosis of mpox in previously-vaccinated individuals.