An Mpox Multi-Antigen-Tandem Bivalent mRNA Candidate Vaccine Effectively Protects Mice Against the Vaccinia Virus.

BACKGROUND: Since the outbreak of mpox in 2022, the disease has spread rapidly worldwide and garnered significant public attention. Vaccination is regarded as an effective measure to prevent the spread of mpox. The success of the COVID-19 mRNA vaccine demonstrates that mRNA-based vaccines represent a rapid and multifunctional platform with considerable potential, and are expected to be a strategy to address mpox spread. METHODS: In this study, we screened an mpox multi-antigen-tandem bivalent mRNA vaccine candidate: a lipid nanoparticle-encapsulated mRNA-1017 and mRNA-1995 (mRNA-3012-LNP). We then evaluated the immunogenicity of the mpox virus (MPXV) bivalent mRNA vaccine candidate and its protective efficacy against the vaccinia virus (VACV) in a mouse model. RESULTS: Mice vaccinated with two doses of the mRNA-3012-LNP vaccine exhibited robust binding antibody responses and MPXV-specific Th-1-biased cellular immune responses in vivo. Notably, the boosted immunized mice generated potent neutralizing antibodies against the VACV, effectively protecting them from viral challenge. Additionally, serum transfer protection experiments indicated that serum from mice inoculated with mRNA-3012-LNP was effective in protecting nude mice from VACV challenge. CONCLUSIONS: Our results suggest that the mpox bivalent mRNA candidate vaccine mRNA-3012-LNP induces strong immunogenicity and has the potential to serve as a safe and effective vaccine candidate against mpox epidemics.