A DNA-based vaccine protects against Crimean-Congo hemorrhagic fever virus disease in a Cynomolgus macaque model

Hawman, David W.; Ahlén, Gustaf; Appelberg, K. Sofia; Meade-White, Kimberly; Hanley, Patrick W.; Scott, Dana; Monteil, Vanessa; Devignot, Stephanie; Okumura, Atsushi; Weber, Friedemann; Feldmann, Heinz; Sällberg, Matti; Mirazimi, Ali

There is currently no specific prophylaxis or vaccine against Crimean-Congo hemorrhagic fever virus (CCHFV). Crimean-Congo hemorrhagic fever (CCHF) is a severe febrile-illness transmitted by Hyalomma ticks in endemic areas, handling of infected livestock or care of infected patients. We report here the successful protection against CCHFV-mediated disease in a non-human primate disease model. Cynomolgus macaques were vaccinated with a DNA-based vaccine using in vivo electroporation-assisted delivery. The vaccine contained two plasmids encoding the glycoprotein precursor (GPC) and the nucleoprotein (NP) of CCHFV. Animals received three vaccinations and we recorded potent antibody and T-cell responses after vaccination. While all sham-vaccinated animals developed viremia, high tissue viral loads and CCHF-induced disease, the NP + GPC vaccinated animals were significantly protected. In conclusion, this is the first evidence of a vaccine that can protect against CCHFV-induced disease in a non-human primate model. This supports clinical development of the vaccine to protect groups at risk for contracting the infection.