Differential immune responses to SFTSV Gn and Gc mRNA vaccines in mice and dogs.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne zoonotic pathogen with high mortality and no licensed vaccines. We developed two lipid nanoparticle-encapsulated mRNA vaccines encoding the Gn and Gc glycoproteins of SFTSV and evaluated their immunogenicity and protective efficacy in mice, as well as their immunogenicity in dogs. In mice, the Gn mRNA vaccine induced higher neutralizing antibody titers and stronger cellular immune responses than the Gc vaccine, and both conferred complete protection against lethal SFTSV challenge in IFNAR-blocked mice. In contrast, in dogs, the Gc mRNA vaccine elicited significantly higher neutralizing antibody titers than Gn, despite comparable safety profiles. This species-dependent divergence in immunogenicity underscores the importance of host-specific considerations in antigen selection for zoonotic vaccine development. These findings support the immunogenic potential of both constructs as candidate vaccines against SFTSV. IMPORTANCE: In this study, we developed mRNA vaccines targeting the severe fever with thrombocytopenia syndrome virus Gn and Gc glycoproteins separately and systematically evaluated their immunogenicity in murine and canine models. Our findings demonstrate that both vaccine formulations effectively elicited potent neutralizing antibody responses in immunized animals. Notably, we observed distinct species-specific immunogenicity patterns: the Gn-targeted vaccine showed superior performance in a murine model, whereas the Gc-targeted variant induced more robust immune activation in beagles. These results emphasize that vaccine selection must account for species-specific efficacy.