Professor, Molecular Biology and Biochemistry
School of Biological Sciences

Major surface proteins and their genes in Trypanosoma cruzi

Trypanosoma cruzi, a parasitic hemo-flagellate, is the causative agent of Chagas disease. This disease constitutes a major health hazard to humans in South and Central America. Thus far, no successful chemotherapeutic cure or immunological prevention has been developed. Since both humans and animals can develop acquired resistance to acute infections of Trypanosoma cruzi, an effective immunophrophylaxis for controlling this parasite should be practical with adequate knowledge. This will include an understanding of the anti-parasite immune responses and a clear distinction between those parasite antigens which do and do not provide immunity. Accordingly, a major emphasis of our research is to identify relevant antigens and to develop methods for acquiring these antigens in sufficient amounts to test their vaccination properties.


Our laboratory has identified three parasite antigens which provide protective immunity to mice against an otherwise lethal challenge by Trypanosoma cruzi. The genes which encode these antigens have been cloned, and these proteins have been expressed in both eucaryotic and procaryotic systems in amounts sufficient for immunological testing.


We are currently mapping the relevant T and B cell epitopes that elicit the protective responses, and studies to determine the immunological basis for protection are in progress. Future studies will include the development of new multiple antigen presenting systems using the selected T and B cell epitopes. Studies to define CD8+ cytolytic epitopes in specific Trypanosoma cruzi antigens are also in progress.

Trifilo, M., Montalto-Morrison, C., Stiles, L.N., Hurst, K.R., Hardison, J.L., Manning, J.E., Masters, P.S. and T.E. Lane. The chemokine CXCL10 controls viral infection in the central nervous system: Evidence for a role in innate immune response through recruitment and activation of Natural Killer cells. J. Virology, in press.

Luhrs K.A., Fouts D.L. and J.E. Manning. Immunization with recombinant paraflagellar rod protein induces protective immunity against Trypanosoma cruzi infection. Vaccine, June 20;21(21-22):3058-69), (2003).

Michailowsky, V., Luhrs, K., Rocha, M.O., Fouts, D.L., Gazzinelli, R.T., and J.E. Manning. Humoral and cellular immune responses to Trypanosoma cruzi-derived paraflagellar rod proteins in patients with Chagas' disease. Infec. Immun., June;71(6):3165-71, (2003).

Wrightsman, R.A., Luhrs, K.A., Fouts, D.L. and J.E. Manning. Paraflagellar rod protein-specific CD8+ cytotoxic T lymphocytes target trypanosoma cruzi-infected host cells. Parasite Immunol., Aug;24(8):401-12, (2002)

Diego, J. L., Katz, J. M., Marshall, P., Gutierrez, B., Manning, J.E., Nussenzweig and J. Gonzalez. The Ubiquitin-Proteasome Pathway Plays An Essential Role in Proteolysis During Trypanosoma cruzi-Remodeling. Biochemistry, 40, 1053-1062. (2001).

Wrightsman, R. A. and J. E. Manning. 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, 1419-1427 (2000).

Quanquin, N. M., Galaviz, C., Fouts, D. L., Wrightsman, R. A., and J. E. Manning. Immunization of Mice with a tolA-like Surface Protein of Trypanosoma cruzi Generates CD4+ T cell-dependent Parasiticidal Activity. Infect. Immun., 67, 4603-4612, (1999).

Giordano, R., Fouts, D.L., Tewari, Colli, W., Manning, J.E. and A. J. M. Alves. Cloning of a Surface Membrane Glycoprotein Specific for the Infective Form of Trypanosoma cruzi Having Adhesive Properties to Laminin. J. Biol. Chem., 274, 3461-3468, (1999).

Fouts, D.L., Stryker, G.A., Gorski, K.S., Miller, M.J., Nguyen, T.V., Wrightsman R.A. and J.E. Manning. Evidence for Four Distinct Major Protein Components in the Paraflagellar Rod of Trypanosoma cruzi. J. Biol. Chem., 273, 21846-21855, (1998).

Biotechnology

Immunology and Pathogenesis

Link to this profile
https://faculty.uci.edu/profile/?facultyId=2143

Last updated
04/18/2005