A single-dose mRNA vaccine protects mice from lethal Crimean-Congo hemorrhagic fever virus infection

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus of the Orthonairovirus genus, Nairoviridae family, that causes severe febrile hemorrhagic disease in humans with a case fatality rate ranging from approximately 3-30%. This zoonotic pathogen is distributed across a broad geographic area spanning Asia, Europe, and Africa. Despite its significant public health threat and outbreak potential, no licensed vaccines are available. In this study, we developed and systematically assessed the immunogenicity and protective efficacy of mRNA vaccines encoding either CCHFV nucleoprotein (NP) or glycoprotein precursor (GPC) in mouse models. Vaccination with the NP-encoding mRNA alone provided complete protection against lethal cross-genotype CCHFV challenge. Moreover, combined vaccination with both the NP and GPC mRNAs elicited robust immune responses and conferred protection against CCHFV infection. Notably, a single-dose immunization with 2 μg mRNA-NP was sufficient to confer protection against lethal challenge. Furthermore, the passive transfer of NP-immune serum provided partial protection, supporting the role of NP-specific antibodies in mediating protection. Overall, these mRNA vaccines demonstrate protective efficacy against CCHFV, with combined antigenic protection and dose-sparing potential, highlighting their potential for outbreak preparedness and further clinical development.