The long-term goal of this project is to select immunogens for the development of a safe and effective vaccine against human lymphatic filariasis. The feasibility of this has been established in studies showing that administration of attenuated larvae or parasite lysates to experimental animals induces partial resistance to challenge with B. malayi infective larvae and reduces the intensity of microfilaremia. Our recent studies indicate that a recombinant protein corresponding to a 63K B. malayi antigen induces resistance to L3 challenge in jirds and microfilaremia in mice and is antigenic in infected humans. To facilitate evaluation of this cloned protein (and other candidate molecules) as a component of an anti-filarial vaccine, the following specific aims are proposed. 1. Define the biochemical structure and function of protective epitopes by evaluating the capacity of full-length and overlapping segments of the cloned antigen to induce resistance to B. malayi in mice and jirds. Subclones encoding potentially protective epitopes will be selected for testing in animals on the basis of immunoreactivity with antibodies and T cells derived from mice immunized with the full-length antigen. 2. Elucidate the immune basis of vaccine-induced resistance in terms of the murine Ig isotype antibodies and helper T cell subsets (TH1 vs TH2) elicited by administrated of the recombinant protein. These data will be related to Ig isotype reactivities to the cloned antigen in humans with Bancroftian filariasis. 3. Design methods to enhance the immunogenicity and protective efficacy of vaccine candidates by delivery in vaccina and Salmonella constructs. Performance of these studies is dependent on Project 2 for molecular cloning of protective antigens and Cores A, B, C, and D for parasites, lymphocyte cloning, and ultrastructural analyses.
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