SFTSV Gn‐Head mRNA vaccine confers efficient protection against lethal viral challenge

Abstract

AbstractSevere fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick‐borne virus, causing thrombocytopenia and hemorrhagic fever, with a fatality rate ranging from 12% to 30%. SFTSV possesses Gn and Gc glycoproteins, which are responsible for host cell receptor attachment and membrane fusion, respectively, to infect host cells. We have previously reported a protein subunit vaccine candidate (sGn‐H‐FT) of the SFTSV soluble Gn head region (sGn‐H) fused with self‐assembling ferritin (FT) nanoparticles, displaying strong protective immunogenicity. In this study, we present messenger RNA (mRNA) vaccine candidates encoding sGn‐H or sGn‐H‐FT, both of which exhibit potent in vivo immunogenicity and protection capacity. Mice immunized with either sGn‐H or sGn‐H‐FT mRNA lipid nanoparticle (LNP) vaccine produced strong total antibodies and neutralizing antibodies (NAbs) against sGn‐H. Importantly, NAb titers remained high for an extended period. Finally, mice immunized with sGn‐H or sGn‐H‐FT mRNA LNP vaccine were fully protected from a lethal dose of SFTSV challenge, showing no fatality. These findings underscore the promise of sGn‐H and sGn‐H‐FT as vaccine antigen candidates capable of providing protective immunity against SFTSV infection.