Clinical and Immunological Efficacy of MVA-BN vaccination against Mpox: results of the prospective AP-HP Monkeyvax study

Background. MVA-BN vaccine is the only effective tool against mpox. It is recommended either as post-exposure prophylaxis (PEP), or pre-exposure prophylaxis (PrEP), with one dose for those vaccinated against smallpox during childhood (born < 1980 in France) and 2 doses otherwise. However, there are limited clinical data on vaccine effectiveness and a lack of standardized tools to monitor vaccine immunogenicity. Those are crucial to adjust current vaccination guidelines and ease vaccination monitoring globally. Our objective was to measure safety, failure rate, humoral and cellular immune response of MVA-BN vaccination in individuals at risk of mpox. Method. The AP-HP Monkeyvax study was a prospective multicentric cohort of individuals vaccinated with MVA-BN vaccine as PEP or PrEP. The primary objective was to estimate the vaccine failure rate, measured as symptomatic mpox confirmed by PCR anytime after PEP or 15 days after the end of primary vaccine schedule for PrEP. Secondary objectives included the evaluation of asymptomatic infection rate, safety, humoral and cellular immune responses, measured by vaccinia virus(VACV) neutralizing antibodies, MSD and Luminex Immuno-assays, and by INF-γ/ IL-2 ELISpot in CD4 + and CD8 + T cells. We compared MVA-BN immunogenicity between participants born before 1980 vaccinated with one dose and participants born ≥ 1980 vaccinated with 2 doses. We examined the correlations between neutralization and immune assays, and between neutralization and T cell response. Results. From July 2022 to October 2023, 164 participants were included, of whom 156 were analyzed: 110 vaccinated as PrEP and 46 as PEP. One symptomatic breakthrough case and one asymptomatic case occurred in the latter group. Higher and durable humoral responses were obtained among those vaccinated with one dose (previous smallpox vaccine during childhood) compared to those vaccinated with 2 doses of MVA-BN as primary vaccine schedule, who have sharp decline after 3 months to low levels at one year. Immuno-assays conducted with the MSD platform showed good correlation with neutralizing antibodies compared to Luminex. CD4 + and CD8 + T cell responses were robust and early in populations, with no correlate found with humoral response. Discussion/conclusion. In this prospective study, two cases of mpox were evidenced after 46 participants were vaccinated as PEP: one symptomatic and one asymptomatic. There were no mpox cases among those vaccinated as PrEP. Humoral immunogenicity declined sharply after 3 months, and reached a low level at 12 months. Our data suggest that immunoassays can help monitor humoral response to MVA-BN vaccine when VACV neutralization is unavailable.