CCHFV-M based DNA vaccine is highly immunogenic in multiple species and protects against challenge in cynomolgus macaques

Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the Nairoviridae family, is the most widely distributed tick-borne virus of medical importance. There are no internationally licensed vaccines, and treatment is limited to supportive care. We previously developed a DNA vaccine expressing the full-length codon-optimized M-segment (CCHFV-M_Afg09), encoding the structural and non-structural viral glycoproteins that protects mice against CCHFV when delivered by intramuscular electroporation (IM-EP). Here, the immunogenicity and protective efficacy of the vaccine delivered by IM-EP was assessed in the non-lethal CCHFV cynomolgus macaque model. The vaccine elicited a significant antibody response to two glycoproteins, the structural G_C and non-structural GP38. CCHFV-M_Afg09 elicited quantifiable T-cell responses directed against the glycoproteins encoded within the M-segment, with anti-G_N immunity reaching significance. Upon intravenous infection with CCHFV, the vaccine protected 5/6 animals against viremia and reduced the pro-inflammatory response compared to sham vaccinated macaques. Numerous macaques also had detectable viral protein and viral RNA in several tissues 28 days post infection. In addition, we determined that an alternative delivery modality, jet injection, was immunogenic in both rabbits and mice, and conferred significant protection in mice. The simplicity and efficacy of disposable syringe needle-free injection system (NFIS) provides a pragmatic approach to advance the CCHF-M DNA vaccine into the clinic. Our M-segment based DNA vaccine elicits both cellular and humoral immunity and significant protection in mice and NHPs, demonstrating for the first time that a vaccine based on the glycoproteins alone is efficacious in the NHP model, which has not previously been shown.