Trypanosoma cruzi is a parasitic hemoflagellate and is the causative agent of Chagas Disease. This parasitic disease constitutes a major human health hazard in South and Central America, and, thus far, no successful chemotherapeutic cure or immunoprophylactic 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 an effective vaccine for prevention and control of the disease should be feasible. Our long term goal continues to be the development of such a vaccine, and the approach which we have taken focuses on utilization of recent advances in the fields of immunology and molecular biology to identify antigens which provide immunoprophylactic protection against the parasite. During the previous granting period we have identified three proteins as vaccine candidates; the paraflagellar rod proteins PAR 1 and PAR 2 and the trypomastigote specific surface glycoprotein TSA- 1. Mice immunized with the paraflagellar rod proteins, PAR 1 and PAR 2, show 100% survival against an otherwise lethal challenge with the parasite, while mice immunized with the NH2 proximal region of TSA-1 show 70% survival against challenge. In continuing these studies, the experiments that! propose for the next granting period are: (1) Define the conditions that will provide optimal immunoprophylactic efficacy against the parasite- derived PAR proteins; (2) Evaluate the immunoprophylactic efficacy of recombinant PAR 1 and PAR 2 proteins; (3) Map the T cell epitopes in PAR 1 and PAR 2 determine whether immunization with these epitopes presented as synthetic peptides provides protection against the parasite; (4) Define the conditions that will provide the optimal immunoprophylactic efficacy of the NH2 proximal region of the TSA-1 molecule; (5) Map the T and B cell epitopes in the NH2 proximal region of TSA-1 and test their vaccine potential when presented as synthetic peptides; (6) Evaluate the vaccine potential of the Tc85 epitope recognized by mabH1A10.
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