Protective efficacy of a bivalent recombinant vesicular stomatitis virus vaccine in the Syrian hamster model of lethal Ebola virus infection.

摘要

BACKGROUND: Outbreaks of filoviral hemorrhagic fever occur sporadically and unpredictably across wide regions in central Africa and overlap with the occurrence of other infectious diseases of public health importance. METHODS: As a proof of concept we developed a bivalent recombinant vaccine based on vesicular stomatitis virus (VSV) expressing the Zaire ebolavirus (ZEBOV) and Andes virus (ANDV) glycoproteins (VSVDeltaG/Dual) and evaluated its protective efficacy in the common lethal Syrian hamster model. Hamsters were vaccinated with VSVDeltaG/Dual and were lethally challenged with ZEBOV or ANDV. Time to immunity and postexposure treatment were evaluated by immunizing hamsters at different times prior to and post ZEBOV challenge. RESULTS: A single immunization with VSVDeltaG/Dual conferred complete and sterile protection against lethal ZEBOV and ANDV challenge. Complete protection was achieved with an immunization as close as 3 days prior to ZEBOV challenge, and 40% of the animals were even protected when treated with VSVDeltaG/Dual one day postchallenge. In comparison to the monovalent VSV vaccine, the bivalent vaccine has slightly reduced postexposure efficacy most likely due to its restricted lymphoid organ replication. CONCLUSIONS: Bivalent VSV vectors are a feasible approach to vaccination against multiple pathogens.