Efficacy of modified-vaccinia Ankara vaccine as pre- and post-exposure prophylaxis against monkeypox sexual transmission in non-human primate model

The monkeypox virus (MPXV) outbreak of 2022 caused a human disease with unusual epidemiological and clinical features, notably an increase in human-to-human transmission through sexual contact, predominantly among men who have sex with men (MSM). This evolution underscores the need to reassess prevention and control strategies in the context of a sexually transmitted disease. Here, we show that rectal challenge of male cynomolgus macaques with a 2022 clade IIb MPXV isolate mimics sexual transmission, leading to rectal infection, with systemic and male genital tract dissemination and seminal fluid shedding. Vaccination with modified-vaccinia Ankara (MVA) protected the macaques from subsequent rectal MPXV challenge. However, MVA failed to prevent the disease when administered four days post-exposure to MPXV. These findings have a critical impact on outbreak management and highlight the importance of reevaluating MVA post-exposure prophylaxis protocols. In 2022, mpox predominantly spread through sexual contact, necessitating updated prevention strategies. Here, the authors show that rectal challenge in male cynomolgus macaques with a 2022 clade IIb MPXV isolate mimics sexual transmission, and that vaccination with modified-vaccinia Ankara protects pre- but not post-exposure.