RESISTANCE OF MICE VACCINATED WITH RABIES VIRUS INTERNAL STRUCTURAL PROTEINS TO LETHAL INFECTION

Mice were vaccinated with recombinant vaccinia virus (rVac) expressing the glycoprotein (G), nucleoprotein (N), phosphoprotein (NS) or matri x protein (M) of rabies virus and their resistance to peripheral letha l infection with street rabies virus was examined. Mice vaccinated wit h rVac-G or rVac-N developed strong antibody responses to the correspo nding proteins and essentially all mice survived challenge infection. Mice vaccinated with rVac-NS or rVac-M developed only a slight antibod y response, however, a significant protection (59%) was observed in th e rVac-NS-vaccinated mice, whereas rVac-M-vaccinated mice were not pro tected. No anti-G antibodies were detected in the sera of mice which h ad been vaccinated with rVac-N or rVac-NS and survived challenge infec tion. Passive transfer of anti-N monoclonal antibodies (MAbs) recogniz ing an epitope located on amino acids 1-224 of the protein prior to ch allenge resulted in significant protection, although the protection wa s not complete even with a high amount of antibodies. In contrast, non e of the mice given MAbs recognizing an epitope of amino acids 247-415 or F(ab')2 fragments from a protective MAb IgG were protected. Admini stration of anti-CD 8 MAb to rVac-N-vaccinated mice showed no signific ant effect on protection. Our observations suggest that a considerable part of the protection achieved by the vaccination with rVac-N can be ascribed to the intact anti-N antibodies recognizing an epitope locat ed on amino acids 1-224 of the protein.