Pre-clinical evaluation of immunogenicity and protective efficacy of a pan-orthoebolavirus virus-like particle (VLP) vaccine 3075

Abstract Description Development of pan-orthoebolavirus vaccines to prevent Ebola disease and to induce durable protective immunity remains an important unmet need. Current Ebola virus (EBOV) vaccines have been reported to protect humans only against EBOV, one of the four pathogenic orthoebolaviruses. Their protective efficacy against Sudan virus (SUDV), Bundibugyo virus (BDBV) and Taï forest virus (TAFV) has not been tested in humans yet. Data from animal studies show that EBOV glycoprotein (GP)-based vaccines protect against EBOV, BDBV and TAFV, but not against SUDV, suggesting that vaccines with GPs from EBOV and SUDV will likely afford pan-orthoebolavirus protection. Here we report the development and pre-clinical evaluation of a bivalent EBOV/SUDV GPs virus-like particle (VLP) vaccine that elicited strong and durable immune responses in rhesus macaques, responses that cross-reacted with and neutralized all pathogenic orthoebolaviruses in GP-based Ebola pseudovirion assays. In a mouse model of Ebola virus disease (EVD), a single shot of this vaccine afforded 100% protection against a lethal dose of mouse-adapted EBOV, protection and lack of EVD signs and symptoms that were comparable to those after vaccination with the FDA-approved rVSV-ZEBOV vaccine. Strong pre-clinical data reported here pave the way for a detailed mechanistic study before advancing this promising pan-orthoebolavirus vaccine into clinical trials. The study was funded, in part, by the Intramural Research Program, NIAID, NIH. Funding Sources Supported by (1) Cincinnati Children’s Innovation Fund, (2) the Intramural Research Program, NIAID, NIH. Topic Categories Vaccines and Immunotherapy (VAC)