IMMUNE CONTROL OF CAE LENTIVIRUS

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Vaccination trials were conducted in outbred Saanen goats using recombinant vaccinia or plasmid DNA vectors expressing the caprine arthritis-encephalitis virus (CAEV) env gene or plasmid DNA expressing CAEV env and tat. Intradermal vaccination with plasmid DNA induced biased type 1 immune responses to vector encoded surface envelope (SU), whereas vaccinia induced type 2 responses. Subcutaneous boost with purified SU in Freund's incomplete adjuvant specifically expanded type 1 or type 2 memory established by initial immunizations with plasmid DNA or vaccinia. These goats together with sham vaccinated and non-vaccinated control goats were challenged intravenously with a molecular clone of tissue culture amplified CAEV. Preliminary results through 24 weeks postchallenge indicate that virus replication is restricted by type 1 immunity induced by plasmid DNA but not by type 2 responses induced by vaccinia. These data provide a basis to determine the role of qualitatively distinct immune responses to lentiviral SU in control of virus replication and disease progression. Therefore, the first objective of this proposal is to test the hypothesis that type 1 immunity induced by plasmid DNA restricts virus replication and prevents development of arthritis following CAEV challenge, whereas type 2 immunity induced by recombinant vaccinia fails to control virus replication and promotes development of arthritis. Proposed experimants expand the preliminary studies to a larger number of animals required for significant evaluation of virus load and disease progression. In addition, the challenge inoculum will be wild type virus derived from field cases of CAE arthritis. Additional goats were co- immunized with plasmid DNA expressing CAEV env with or without tat together with a second plasmid DNA encoding caprine interferon gamma (IFN). These studies provide preliminary evidence that synergistic effects of plasmid encoded Tat and IFN inhibit primary adaptive B cell responses to plasmid encoded SU without effect on activation of SU responsive Th1 lymphocytes. Significant control of CAEV replication by goats with this vaccine induced immunologic profile will support further studies on the role of Tat and IFN as vaccine components. Therefore, the second objective of this proposal is to evaluate virus replication following CAEV challenge of goats co-immunized with plasmid DNA expressing CAEV env and tat genes and caprine IFN.