Crimean-Congo hemorrhagic fever virus protein GP38 from isolate M18-China confers broad immunological breadth

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne, negative-strand RNA virus that causes outbreaks of lethal hemorrhagic fever. No approved vaccines or specific antiviral treatments are available. CCHFV glycoprotein GP38 is an integral component of the pre-fusion glycoprotein entry complex, plays roles in viral pathogenesis, and is a key target of antibody-mediated protection. Herein, we investigated the hypothesis that recombinant GP38 itself could elicit protection against divergent CCHFV isolates/strains in an animal model. Accordingly, we generated GP38 immunogens from six CCHFV clades and showed that GP38 from the isolate M18-China induces a broad immunological response in mice despite its lower amino acid sequence similarity to other isolates. We identified sequences in M18-China GP38 associated with this immunological breadth and evaluated it as a vaccine candidate. Although M18-China GP38 was not protective in isolation, our findings warrant further exploration of its utility as one component of a broadly protective CCHFV vaccine.