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Infection and Immunity, October 2002, p. 5547-5555, Vol. 70, No. 10
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.10.5547-5555.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Genetic Immunization Elicits Antigen-Specific Protective Immune Responses and Decreases Disease Severity in Trypanosoma cruzi Infection

Nisha Garg{dagger} and Rick L. Tarleton*

Center for Tropical and Emerging Infectious Diseases and Department of Cellular Biology, University of Georgia, Athens, Georgia 30602

Received 13 February 2002/ Returned for modification 12 April 2002/ Accepted 12 July 2002

Immunity to Trypanosoma cruzi requires elicitation of humoral and cell-mediated immune responses to extracellular trypomastigotes and intracellular amastigotes. In this study, the effectiveness of the T. cruzi trans-sialidase family (ts) genes ASP-1, ASP-2, and TSA-1 as genetic vaccines was assessed. Immunization of mice with plasmids encoding ASP-1, ASP-2, or TSA-1 elicited poor antigen-specific cytotoxic-T-lymphocyte (CTL) activity and T. cruzi-specific antibody responses. Codelivery of interleukin-12 and granulocyte-macrophage colony-stimulating factor plasmids with antigen-encoding plasmids resulted in a substantial increase in CTL activity and antibody production and in increased resistance to T. cruzi infection. In pooled results from two to four experiments, 30 to 60% of mice immunized with antigen-encoding plasmids and 60 to 80% of mice immunized with antigen-encoding plasmids plus cytokine adjuvants survived a lethal challenge with T. cruzi. In comparison, 90% of control mice injected with empty plasmid DNA died during the acute phase of infection. However, the pool of three ts genes provided no greater protection than the most effective single gene (ASP-2) either with or without coadministration of cytokine plasmids. Importantly, the extent of tissue parasitism, inflammation, and associated tissue damage in skeletal muscles during the chronic phase of T. cruzi infection in mice immunized with antigen-encoding plasmids plus cytokine adjuvants was remarkably reduced compared to mice immunized with only cytokine adjuvants or empty plasmid DNA. These results identify new vaccine candidates and establish some of the methodologies that might be needed to develop effective vaccine-mediated control of T. cruzi infection. In addition, this work provides the first evidence that prophylactic genetic immunization can prevent the development of Chagas’ disease.

* Corresponding author. Mailing address: Department of Cellular Biology, University of Georgia, Athens, GA 30602. Phone: (706) 542-3362. Fax: (706) 542-4271. E-mail: tarleton{at}cb.uga.edu.

Editor: J. M. Mansfield

{dagger} Present address: Departments of Microbiology and Immunology and Pathology, University of Texas Medical Branch, Galveston, TX 77555.

Infection and Immunity, October 2002, p. 5547-5555, Vol. 70, No. 10
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.10.5547-5555.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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