This proposal is a continuation of an existing project for the development of a vaccine strategy for the prevention of human T- cell leukemia virus type I (HTLV-I) infection and associated disease. The approach has been to evaluate the methodology successfully developed in the feline leukemia virus (FeLV) vaccine. This approach has included the preparation, characterization and demonstration of the immunogenicity of the vaccine. The vaccine is produced from the HTLV-I persistently infected cell line MT-2. Molecular sizing liquid chromatography, SDS-PAGE and immunoblot (Dot and Western Blotting) analysis has demonstrated that the vaccine materials is composed of HTLV-I-specific antigens including the envelope (gp68 and gp46) and the core (p24 and p19) polypeptides of the HTLV-I virion. Flow cytometric analysis has revealed that these products are expressed maximally during the G2/M phase of the cell cycle, and these results have been used to optimize vaccine production. The safety and efficacy of this vaccine preparation remains to be established, however, no infectious virus can be demonstrated in the vaccine material and the vaccine induces both neutralizing and complement-fixing antibody in the rabbit and in the pig-tailed macaque. We conclude that the development of a vaccine to prevent HTLV-I infection and associated disease is feasible. In addition to the production of a vaccine candidate for human use, it is predicted that the definition of a macaque challenge animal model will lead to a better understanding of the virology and immunology of retroviral-host interactions, in particular the primary response to infection including the development of latency an HTLV-I- associated malignancy. Furthermore, it is predicted that the mechanism(s) which induce the protective response(s) against retroviral infection (HTLV-I) may be further understood.
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