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-Swildtype), 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.
Flory
E
E
Institute of Virology and Immunobiology, University of Würzburg, FRG.
Pfleiderer
M
M
Stühler
A
A
Wege
H
H
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D016827:CD8 Antigens / Q000032:analysis; D003333:Coronaviridae Infections / Q000276:immunology*; D004679:Encephalomyelitis / Q000276:immunology*; D007114:Immunization; D006517:Murine hepatitis virus / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D016827:CD8 Antigens; D014614:Vaccines, Synthetic; D014765:Viral Vaccines