Date of Award

1992

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical and Veterinary Medical Sciences - Comparative Biomedical Sciences

First Advisor

David W. Horohov

Abstract

The lentivirus Equine Infectious Anemia Virus (EIAV) causes an acute infection in horses which is characterized by fever, viremia, thrombocytopenia, edema, and hemolytic anemia. Most horses survive the acute disease, but remain persistently infected for life. The exact mechanism whereby horses' control their initial infection is unknown, though it appears likely that cellular immune mechanisms are involved. T lymphocytes have been shown to play a major role in the recovery from a variety of viral infections, though their role in EIAV infection has not been established. We tested peripheral blood mononuclear cells (PBMC) from EIAV-infected ponies for evidence of a cell-mediated immune response to this virus. PBMC from infected ponies exhibited EIAV-specific lymphoproliferation upon in vitro stimulation with viral antigen. Cytolytic effector cell activity of these cells was determined by lectin-mediated cytotoxicity assays and by the production of serine esterase. To investigate the role of cell-mediated immune responses in protection from EIAV-induced disease, the T cell responses to EIAV in vaccinated ponies were analyzed. Ponies were vaccinated with an inactivated EIAV whole virus vaccine or a subunit vaccine enriched in EIAV envelope glycoproteins. The in vitro lymphoproliferative response was shown to be mediated by T lymphocytes and was indistinguishable from that induced by EIAV infection. Although both vaccines stimulated EIAV-specific cell-mediated immunity, upon in vivo challenge with virulent or avirulent EIAV it was determined that the whole virus vaccine conferred protection while the subunit vaccine appeared to exacerbate disease. EIAV specific cell-mediated immunity was also demonstrated by antigen specific proliferation of T cells from infected and vaccinated ponies in response to viral proteins and peptides. By identifying the segments of gp90 and gp45 that were reactive in these cell-mediated immune response assays, this study will aid in the development of possible vaccines against EIAV and other related retroviruses including HIV-1.

Pages

96

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