Trypanosoma cruzi is a parasitic protozoan and is the causative agent of Chagas' disease. This disease is prevalent throughout most of Central and South America and constitutes a major health hazard. At present, no successful chemotherapeutic treatment or immunoprophylactic protection against the parasite is available. Our long term goal has been the development of an efficacious vaccine for disease prevention and control of the parasite. The approach that we have taken focuses on utilization of recent advances in the fields of immunology and molecular biology to identify antigens that provide immunoprophylactic protection against the parasite. Our recent studies have identified a group of four candidate antigens present in the paraflagellar rod (PAR) of the parasite. These antigens, designated PAR proteins 1-4, when used as immunogens in the mouse model provide 100 percent survival against an otherwise lethal challenge with the parasite. These findings introduce the possibility that these antigens may be useful as protective immunogens in humans. To investigate this possibility, studies to define the pattern of recognition of the PAR proteins by the immune system of Chagasic patients with well defined clinical symptoms are proposed. The experiments that we propose are: (1) Determine whether the four PAR proteins identified in the Peru and Esmeraldo strains of T. cruzi also are present in different T. cruzi isolates obtained from widely separated geographical areas of Brazil, (2) Define the humoral immune response against the PAR proteins in clinically characterized Chagasic patients, (3) Define the cellular immune response against the PAR proteins in clinically characterized Chagasic patients.
