Assessment of a vesicular stomatitis virus-based vaccine by use of the mouse model of Ebola virus hemorrhagic fever

Background. In humans and nonhuman primates, Ebola virus causes a virulent viral hemorrhagic fever for which no licensed vaccines or therapeutic drugs exist. In the present study, we used the mouse model for Ebola hemorrhagic fever to assess the safety and efficacy of a vaccine based on a live attenuated vesicular stomatitis virus expressing the Zaire ebolavirus (ZEBOV) glycoprotein. Methods. Healthy mice were given the vaccine in various doses, decreasing from 2 X 10(4) to 2 plaque-forming units (pfu), with both systemic and mucosal vaccination routes used. Mice were challenged with to 10(3) to 10(6) lethal doses of mouse-adapted ZEBOV. Severely immunocompromised mice were injected with 2 X 10(5) pfu, which is 10 times greater than the immunization dose normally used, to test vaccine safety. Results. Two plaque-forming units of the vaccine protected against lethal challenge, and mucosal immunization was found to be as protective as systemic injection. The replicating vaccine was never detected in the immunized animals, nor were there clinical signs after immunization. Immunization of severely immunocompromised mice with 200,000 pfu of vaccine resulted in no clinical symptoms. Conclusions. Our data suggest that the vaccine is highly potent and safe and that it very rapidly induces "sterile" immunity in mice. The potential for mucosal delivery, if confirmed in nonhuman primates, makes it an excellent candidate for mass immunization during outbreaks or in the event of intentional release.