INDUCTION OF PROTECTIVE IMMUNITY AGAINST CORONAVIRUS-INDUCED ENCEPHALOMYELITIS - EVIDENCE FOR AN IMPORTANT ROLE OF CD8-CELLS IN-VIVO( T)

Coronavirus MHV-JHM infections of rats provide useful models to study the pathogenesis of virus-induced central nervous system disease.To an alyze the role of the immune response against defined MHV-JHM antigens , we tested the protective efficacy of vaccinia virus (VV) recombinant s expressing either the nucleocapsid (N) or the spike (S) protein. A s trong protection was mediated in animals by immunization with recombin ant VV encoding a wild-type S protein (VV-S(wildtype)), whereas VV rec ombinant expressing a mutant S354CR protein (VV)S354CR) had no protect ive effect. Recombinant VV encoding N protein (VV-N) induces a humoral and a CD4+ T cell response, but did not prevent acute disease regardl ess of the immunization protocol. In these experiments, challenge with an otherwise lethal dose of MHV-JHM was performed prior to the induct ion of virus-neutralizing antibodies and studies with the anti-CD8+ mo noclonal antibody, MRC OX8 showed that elimination of the CD8+ subset of T cells abrogates the protective effect. This result indicates that CD8+ T cells primed by recombinant VV expressing wild-type S protein are a primary mechanism of immunological defense against MHV-JHM infec tion in rats.