Waning humoral immunity following monkeypox virus infection and vaccination, Canada, 2020 to 2023

BACKGROUNDMonkeypox 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.AIMWe 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.METHODSThis 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.RESULTSMonitoring 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.CONCLUSIONAs 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.