Trypanosoma cruzi is a parasitic hemoflagellate and is the causative agent of Chagas Disease. This parasitic disease constitutes a major health hazard to man in South and Central America and, thus far, no successful chemotherapeutic cure or immunological methods to prevent infection have been developed. Since both man and experimental animals can develop acquired resistance against acute infections of T. cruzi, the development of effective immunoprophylaxis for prevention and control of this parasite should be feasible with adequate knowledge. The latter will certainly include an understanding of the antiparasite immune responses and a clear distinction between those parasite antigens which may provide protection and those which might contribute to immunopathological damage in the host. The ability to clearly identify and isolate or synthesize relevant parasite antigens would be of tremendous value in these areas. Accordingly, the major emphasis of the experiments proposed in this grant is directed toward the identification of relevant antigens on the surface of the parasite and development of methods for the procurement of these antigens in sufficient quantities to test their vaccination properties. Specifically, we plan to isolate the 85 and 90 kDa trypomastigote surface antigens and test their ability to provide protective immunity to mice against a T. cruzi challenge; (2) To determine whether monoclonal antibodies against these antigens can confer protection to mice against an otherwise lethal inoculum of parasites; (3) To characterize the gene(s) which encodes these surface antigens; (4) To determine the extent and molecular basis of antigenic diversity among different isolates of T. cruzi; (5) To define on the antigen gene sequence those regions which encode the antigenic determinants recognized by the host immune system; (6) To determine the feasibility of either producing specific antigens in large amounts by use of recombinant DNA technology or chemically synthesizing peptides which correspond to the antigenic determinants.
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