Gc glycoprotein trimer vaccine elicits robust neutralizing antibodies against severe fever with thrombocytopenia syndrome virus in mice.

Severe fever with thrombocytopenia syndrome virus (SFTSV) has been widely spread both domestically and internationally, with a mortality rate of up to 30 %; but no vaccine is currently available. During viral invasion, the glycoproteins Gn and Gc, which serve as the primary antigens, can exist in various natural conformations, including monomers and homo/hetero polymers. However, the role of these structural variations in activating immune response remains unclear. This study aimed to identify antigen formations with high immunogenicity by constructing protein vaccines with different structural configurations: Gn or Gc monomer, dimer, and trimer. The induced humoral and cellular immunity were assessed in mice. The results demonstrated that the Gn trimer induced higher antibody levels than the Gn dimer and recognized more SFTSV strains compared to those induced by the Gn monomer. Additionally, Gc trimer exhibited superior immunogenicity, inducing higher neutralizing antibody production than other groups (Gn monomer, Gn dimer, Gn trimer, and Gc dimer), and antibodies induced by Gc trimer can even recognized all of the six wild type strains used in this study. Furthermore, monomers and trimers of Gn or Gc elicited high levels of Th1 and Th2 cytokines, and antibody-dependent cellular cytotoxicity (ADCC) responses. However, Gn trimer provided more protective efficacy than Gn monomer, whereas Gc monomer and trimer provided complete protection against SFTSV in virus challenge experiment based on pseudovirus. These findings identify the dominant antigenic structures of SFTSV that are more effective in stimulating neutralizing antibody production. This discovery may offer novel targets and strategies for enhancing immunogenicity in the development of SFTSV vaccines.