SAFETY, IMMUNOGENICITY, AND EFFICACY OF INTRAMUSCULAR AND ORAL DELIVERY OF ERA-G333 RECOMBINANT RABIES VIRUS VACCINE...

Attenuated strains of rabies virus (RABV) have been used for oral vaccination of wild carnivores in Europe and North America. However, some RABV vaccines caused clinical rabies in target animals. To improve the safety of attenuated RABV as an oral vaccine for field use, strategies using selection of escape mutants under monoclonal antibody neutralization pressure and reverse genetics-defined mutations have been used. We tested the safety, immunogenicity, and efficacy of one RABV construct, ERA-g333, developed with reverse genetics by intramuscular (IM) or oral (PO) routes in big brown bats (Eptesicus fuscus). Twenty-five bats received 5×10⁶ mouse intracerebral median lethal doses (MICLD₅₀) of ERA-g333 by IM route, 10 received 5×10⁶ MICLD₅₀ of ERA-g333 by PO route, and 22 bats served as unvaccinated controls. Twenty-one days after vaccination, 44 bats were infected by IM route with 10^2.9 MICLD₅₀ of E. fuscus RABV. We report both the immunogenicity and efficacy of ERA-g333 delivered by the IM route; no induction of humoral immunity was detected in bats vaccinated by the PO route. Two subsets of bats vaccinated IM (n=5) and PO (n=3) were not challenged, and none developed clinical rabies from ERA-g333. Scarce reports exist on the evaluation of oral rabies vaccines in insectivorous bats, although the strategy evaluated here may be feasible for future application to these important RABV reservoirs.