Circular RNA Vaccines Encoding Fusion Proteins of Mpox Virus A35R-M1R and B6R-A29L Induce Robust and Durable Protective Immunity in Mice

Developing a safe and effective vaccine is crucial to control the recent worldwide outbreaks of mpox. Here, building upon our previously established lipid nanoparticle (LNP)-encapsulated circRNA vaccine platform, we constructed two bivalent mpox virus (MPXV) circRNA vaccines: cirBA encoding a B6R-A29L tandem antigen and cirAM encoding an A35R-M1R fusion antigen. Both bivalent MPXV circRNA vaccines, whether administered alone or in combination (designated cirMix), could induce robust and durable MPXV antigen-specific humoral and cellular immune responses in mice, conferring complete protection against lethal vaccinia virus Tian Tan strain (VTT) challenge. Moreover, even at low doses (2 µg for cirBA and cirAM, 4 µg for cirMix), all circRNA vaccines could provide 100