The principal investigator proposes to test the hypothesis that conserved equine infectious anemia virus (EIAV) protein epitopes identified by CTLm from carrier horses can be used to induce protective immune responses in naive horses. The research will focus on experiments that may provide conclusive evidence for the role of CD8+ CTL in EIAV control. Most immunocompetent horses terminate the initial viremia and recurrences of viremia to eventually become inapparent carriers with very low levels of virus. Termination of viremia requires lymphocyte responses; these appear to be more concordant with virus downregulation than do neutralizing antibodies, which appear after viremia has been terminated. With the intent of providing data concerning a cause/effect relationship between MHC class I-restricted CD8 CTL and control of EIAV infection, the principal investigator will address four specific aims: (1) To identify conserved EIAV epitopes recognized by alloantigen ELA-A5-restricted memory CTL (CTLm) from carrier horses; (2) to induce CTLm in horses with a retroviral vector expressing conserved CTL epitopes; (3) to determine whether or not co- expression of equine IL-12 and CTL epitopes by a retroviral vector will increase the frequency of CTLm; and (4) to determine whether or not immunized horses expressing at least one ELA-A5 allele are protected from or more efficiently control EIAV infection and disease following virus challenge.
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