Induction of protective immunity against coronavirus‐induced encephalomyelitis: Evidence for an important role of CD8(+) T cells in vivo

Flory, Egbert; Pfleiderer, Michael; And, Albert Stühler; Wege, Helmut

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 S(354CR) protein (VV‐S(354CR)) 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.