Abstract
BACKGROUND: Monkeypox virus (MPXV) has spread globally to non-endemic countries in recent years and has the potential to cause recurrent outbreaks. Vaccine breakthrough infections and reinfections are suggested to be linked to immunity waning over time. AIM: We aimed to determine how long individuals remain protected following MPXV infection and if vaccination can be used as a public heath measure to elicit durable protective immune responses. METHODS: This retrospective observational study investigated the durability of humoral immune responses in a longitudinal cohort of 46 individuals infected with MPXV during the 2022 global mpox outbreak. We collected 86 blood samples up to 7 months after infection, and analysed the antibody responses against MPXV with a serological assay using a panel of eight viral antigens. RESULTS: Monitoring of antibody kinetics revealed transient IgM responses in the first weeks following infection and a robust polyclonal IgG response that peaked 1–2 months after infection but declined consistently in the following months. Post-exposure immunisation with third-generation modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine did not seem to increase significantly the strength, breadth or longevity of antibody responses. Using a separate cohort of 25 uninfected long-term MVA-BN vaccinees, we observed low to undetectable seropositivity against most MPXV antigens after 30 months. CONCLUSION: As circulating antibody titres have been identified as a correlate of protection against mpox, declining antibody levels raise concerns for mpox susceptibility in previously infected and vaccinated persons. This warrants further evaluation of long-term vaccine effectiveness to inform booster vaccination guidance.