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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Irvine
Schools of Arts and Sciences
United States
Zip Code
Hardison, Jenny L; Wrightsman, Ruth A; Carpenter, Philip M et al. (2006) The CC chemokine receptor 5 is important in control of parasite replication and acute cardiac inflammation following infection with Trypanosoma cruzi. Infect Immun 74:135-43
Hardison, Jenny L; Wrightsman, Ruth A; Carpenter, Philip M et al. (2006) The chemokines CXCL9 and CXCL10 promote a protective immune response but do not contribute to cardiac inflammation following infection with Trypanosoma cruzi. Infect Immun 74:125-34
Hardison, Jenny L; Kuziel, William A; Manning, Jerry E et al. (2006) Chemokine CC receptor 2 is important for acute control of cardiac parasitism but does not contribute to cardiac inflammation after infection with Trypanosoma cruzi. J Infect Dis 193:1584-8
Wrightsman, Ruth A; Luhrs, Keith A; Fouts, David et al. (2002) Paraflagellar rod protein-specific CD8+ cytotoxic T lymphocytes target Trypanosoma cruzi-infected host cells. Parasite Immunol 24:401-12
Wrightsman, R A; Manning, J E (2000) Paraflagellar rod proteins administered with alum and IL-12 or recombinant adenovirus expressing IL-12 generates antigen-specific responses and protective immunity in mice against Trypanosoma cruzi. Vaccine 18:1419-27
Giordano, R; Fouts, D L; Tewari, D et al. (1999) Cloning of a surface membrane glycoprotein specific for the infective form of Trypanosoma cruzi having adhesive properties to laminin. J Biol Chem 274:3461-8
Quanquin, N M; Galaviz, C; Fouts, D L et al. (1999) Immunization of mice with a TolA-like surface protein of Trypanosoma cruzi generates CD4(+) T-cell-dependent parasiticidal activity. Infect Immun 67:4603-12
Fouts, D L; Stryker, G A; Gorski, K S et al. (1998) Evidence for four distinct major protein components in the paraflagellar rod of Trypanosoma cruzi. J Biol Chem 273:21846-55
Miller, M J; Wrightsman, R A; Stryker, G A et al. (1997) Protection of mice against Trypanosoma cruzi by immunization with paraflagellar rod proteins requires T cell, but not B cell, function. J Immunol 158:5330-7
Miller, M J; Wrightsman, R A; Manning, J E (1996) Trypanosoma cruzi: protective immunity in mice immunized with paraflagellar rod proteins is associated with a T-helper type 1 response. Exp Parasitol 84:156-67

Showing the most recent 10 out of 23 publications