Immune Response to MVA-BN Vaccination for Mpox: Current Evidence and Future Directions

The 2022 global mpox outbreak, caused by clade IIb of the monkeypox virus (MPXV), prompted emergency use authorisation of the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine, previously approved for smallpox prevention. Understanding immune responses to the MVA-BN vaccine is critical to inform both current and future mpox vaccine policy, particularly amid reports of breakthrough infections in vaccinated persons, uncertainty about the durability of vaccine-induced protection, and the emergence of further outbreaks of mpox from different viral clades, including the clade I-driven public health emergency of international concern. MVA-BN elicits binding and neutralising antibody, memory B cells, and T cell responses. Immune responses vary by host factors, prior orthopoxvirus exposure, and dosing regimens. While seroconversion is generally robust, circulating antibody titres often wane rapidly, particularly in vaccinia-naïve and/or immunocompromised individuals, including people with HIV. Vaccine-induced neutralising antibody responses to MPXV are frequently lower than to vaccinia virus, and their role in protection remains ill-defined. In contrast, T cell responses appear more sustained and may support long-term immunity in the absence of persistent antibody titres. This narrative review synthesises current evidence on the immunogenicity and durability of MVA-BN vaccination, highlights challenges in assay interpretation, and outlines key research priorities, including the need to explore correlates of protection, booster strategies, and next-generation vaccine design.