A replicating RNA vaccine confers protection against Crimean-Congo hemorrhagic fever in cynomolgus macaques.

BACKGROUND: Crimean-Congo hemorrhagic fever is a tick-borne febrile illness with wide geographic distribution. In recent years the geographic range of CCHFV and its tick vector have increased, placing an increasing number of people at risk of CCHFV infection. Currently there are no widely available vaccines and although the World Health Organization recommends ribavirin for treatment, its efficacy is unclear. Vaccines are critically needed for CCHFV. METHODS: Here we evaluated a promising replicating RNA vaccine for CCHFV in a Cynomolgus macaque model of disease. FINDINGS: In primed and boosted macaques, we found that our replicating RNA vaccine expressing the CCHFV nucleoprotein (repNP) was highly immunogenic, eliciting a robust non-neutralizing antibody response that conferred significant protection against CCHFV challenge. Macaques receiving a single repNP vaccination were partially protected against CCHFV challenge. INTERPRETATION: Our data demonstrate that our repNP vaccine and NP-specific antibody can protect against CCHFV in non-human primates. FUNDING: This study was supported by the Intramural Research Program of the NIAID/NIH and the Medical CBRN Defense Consortium grant #MCDC2204-011.