VACCINE FOR EQUINE INFECTIOUS ANEMIA VIRUS VARIANTS

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Retroviruses cause diseases in humans and animals, ranging from neoplasia to immunosuppression. Lentiviruses (a non-oncogenic subfamily) are comprised of the HTLV-III/LAV/ARV human virus group; the small ruminant virus group of caprine arthritis-encephalitis, visna and progressive pneumonia viruses; and equine infectious anemia virus (EIAV). Control of lentiviruses is difficult because of provirus persistence and changes in the env gene sequence resulting in antigenic variation of surface glycoproteins. The long term objective of this proposal is to understand the structural organization of critical functional regions of surface glycoproteins of EIAV, a unique retrovirus for studies of antigenic variation and persistence. This investigation will examine how a single functional region--the receptor binding site--can be used to elicit a neutralizing antibody response that reacts with EIAV antigenic variants. The protective effects of these antibodies both alone and in conjunction with a cytotoxic T lymphocyte response directed against invariant EIAV antigens on infected cells will then be evaluated. The methods will include isolating a receptor binding site from purified virion surface glycoproteins by proteolytic digestion and HPLC, constructing a binding site receptor analog by peptide synthesis or by expression of cloned env gene in a vector system, immunizing horses with the receptor binding site analog and with invariant EIAV antigens that stimulate cytotoxic T lymphocytes and challenging immunized horses with EIAV antigenic variants. The specific aims are: 1. To determine whether antigenic variants of EIAV have a common receptor binding site. 2. To isolate and characterize a fragment of viral gp90 containing the receptor binding site. 3. To make a synthetic or recombinant product immunochemically analogous to the receptor binding site. 4. To test the capacity of the receptor binding site analog to elicit a cross protective immune response in horses against EIAV antigenic variants. 5. To demonstrate that immunization with an invariant EIAV antigen that stimulates cytotoxic T lymphocytes will augment immunication with a receptor binding site analog.