A single-chain mRNA vaccine co-expressing GPC and NP provides complete protection against lethal Dabie bandavirus challenge in mice.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever caused by Dabie bandavirus (DBV), with a fatality rate of up to 30%. However, no approved vaccines or specific therapeutics against the virus are available yet. Here, we engineered a novel mRNA vaccine (GFN-LNP) featuring a single-chain design that incorporates both glycoprotein precursor (GPC) and nucleoprotein (NP) antigens connected by a (G4S1)3 flexible linker. A comparative evaluation was performed against three control formulations GPC (GPC-LNP), NP (NP-LNP), and physically mixed GPC-LNP/NP-LNP (Mix). Immunological assessments revealed that both GPC-LNP and GFN-LNP formulations induced robust humoral and cellular immune responses in mouse models. Remarkably, all multiantigen formulations (GPC-LNP, Mix, and GFN-LNP) conferred complete protection against lethal DBV challenge in A129 mice, as evidenced by the absence of weight loss, mortality, or detectable infectious virions in major organs. Immunohistochemistry analysis further demonstrated the superior efficacy of GFN-LNP, with no viral antigen detected in organ sections post-challenge. The dual-antigen GFN-LNP formulation additionally presented the unique advantage of maintaining hematological parameters within normal ranges following viral exposure. These findings collectively establish that our innovative single-chain, dual-antigen mRNA design (GFN-LNP) combines manufacturing efficiency with exceptional protective efficacy, positioning it as a leading vaccine candidate against DBV.