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

Coronavirus MHV-JHM infections of rats provide useful models to study the pathogenesis of virus-induced central nervous system disease.To analyze the role of the immune response against defined MHV-JHM antigens, we tested the protective efficacy of vaccinia virus (VV) recombinants expressing either the nucleocapsid (N) or the spike (S) protein. A strong protection was mediated in animals by immunization with recombinant VV encoding a wild-type S protein (VV-S(wildtype)), whereas VV recombinant expressing a mutant S354CR protein (VV)S354CR) had no protective effect. Recombinant VV encoding N protein (VV-N) induces a humoral and a CD4+ T cell response, but did not prevent acute disease regardless of the immunization protocol. In these experiments, challenge with an otherwise lethal dose of MHV-JHM was performed prior to the induction of virus-neutralizing antibodies and studies with the anti-CD8+ monoclonal 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 infection in rats.