The research will delineate the important immunogens of Trypanosoma cruzi in an immunization induced resistant mouse model. Immunization of C3H(He) mice with live Corpus Christi strain T. cruzi prior to infection with the virulent Brazil strain results in up to 100% survival compared to 100% mortality in unimmunized mice. Mice which survive acute infection have high titer parasite specific antibody which cross reacts with many T. cruzi strains. Others have found parasite antigens to cross react with host tissue and assume these to play a role in the induction of chronic autoimmune pathology. This host-parasite system will be used to delineate the probable immunogens responsible for protective responses in acute infection and those immunogens responsible for pathology in chronic infection. The experimental approach is to electrophoretically separate and characterize the antigens from the parasite strains (Brazil, Corpus Christi, Y, Tulahuen), and using Western Blot analysis, identify the immunogens which are responded to by mice immunized and/or infected. By using sera from mice acutely infected as the probe in the Western Blots, the immunogens responded to during acute phase protection and chronic phase pathology will be labeled. Monoclonal antibodies, which have been found to react with the parasite strains tested, will be tested for their ability to specifically bind to the immunogens by Western Blot analysis and selected monoclonals will then be used in immunoaffinity chromatography to isolate the immunogens of interest. The cellular (measured by lymphocyte blastogenesis) and humoral (measured by enzyme linked immunoassay) response to these immunogens will be monitored in immunized, infected or immunized and infected mice through infection. The information obtained in this investigation will be the basis of future projects such as vaccination studies and examination of the mechanisms of protective and pathogenic responses. The importance of this project results from the lack of an acceptable vaccine for Chagas' Disease, which is caused by T. cruzi infection. This disease effects over 12 million people in South and Central America and chronic Chagas' Disease results in the most common heart ailment in these regions.
