INVOLVEMENT OF GAG-SPECIFIC AND ENV-SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN PROTECTIVE IMMUNITY TO FELINE IMMUNODEFICIENCY VIRUS

Definition of the immunological mechanisms involved in protective immu nity against lentiviral infections is crucial to the development of an effective vaccine, The induction of gag- and env-specific cell-mediat ed immune responses was studied in cats following vaccination with who le inactivated feline immunodeficiency virus (FIV). Cats were immunize d by inoculation with three doses of paraformaldehyde-inactivated FIV derived from the feline lymphoid cell line, FL-4, which is persistentl y infected with the Petaluma isolate of FIV, Autologous or allogeneic skin fibroblasts either infected with recombinant FIV gag- or env-vacc inia virus or pulsed with FIV env peptides were used as targets in chr omium-51 release assays, Effector cells were fresh peripheral blood mo nonuclear cells, Following the third immunization, all vaccinated cats , but none of the control cats immunized with adjuvant alone, had dete ctable FIV env-specific lymphocytotoxicity in their peripheral blood, Two cats also exhibited gag-specific activity, There was no recognitio n of either allogeneic skin fibroblasts infected with recombinant vacc inia virus or autologous target cells infected with wild-type vaccinia virus, indicating the specificity and MHC-restricted nature of the re sponse. Vaccinated cats, but not control cats, were protected from cha llenge with the homologous Petaluma isolate of FIV. Partial epitope ma pping of the env-specific cytotoxic response was performed using overl apping 10-amino acid peptides from the env V3 domain of FIV, This resp onse appeared to be directed at env peptide 1 (RAISSWKQRN) and env pep tide 3 (QRNRWEWRPD), which lie adjacent to a beta-turn within the V3 d omain, This study clearly demonstrates that both gag- and env-specific lymphocytotoxicity are induced following vaccination of cats with who le inactivated FIV and thus contribute to the protective immunity obse rved in these animals.