Self-Replicating RNA vaccine for crimean-congo hemorrhagic fever virus protects via non-neutralizing anti-NP antibodies

Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a negative sense, RNA bunyavirus prevalent across Europe, Asia, and Africa. CCHFV infection causes a non-specific febrile illness which may progress into a severe, hemorrhagic disease with case fatality rates as high as 70%. However, there is a lack of approved interventions and correlates of protection lending to countermeasure development are not well understood. Therefore, CCHFV is listed as a high priority pathogen by the World Health Organization.

Recently, we reported high protective efficacy of a self-replicating RNA vaccine which expresses the CCHFV nucleoprotein (NP). This vaccine induces high titers of non-neutralizing anti-NP antibodies. Depletion of T-cells post-vaccination and prior to challenge did not significantly affect vaccine efficacy, indicating that the anti-NP antibodies are the primary correlate of protection. As the CCHFV-NP is not expressed on the cell or virion surface, these antibodies may protect through classical and non-classical functions. Currently, we are evaluating this vaccine’s protective efficacy in mice deficient in several Fc-effector functions such as activation of Fc-receptors and complement to investigate the role of these pathways in vaccine protection. Overall, understanding the mechanisms of protection by this vaccine will support much-needed countermeasure development against CCHF. This work was funded by the NIH Intramural Research Program.