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Clinical and Vaccine Immunology, August 2008, p. 1158-1164, Vol. 15, No. 8
1071-412X/08/$08.00+0     doi:10.1128/CVI.00144-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Previously Unrecognized Vaccine Candidates Control Trypanosoma cruzi Infection and Immunopathology in Mice {triangledown}

Vandanajay Bhatia1 and Nisha Jain Garg1,2,3*

Departments of Microbiology and Immunology,1 Pathology, University of Texas Medical Branch, Galveston, Texas,2 Center for Biodefense and Emerging Infectious Diseases and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas3

Received 25 April 2008/ Returned for modification 28 May 2008/ Accepted 4 June 2008

Trypanosoma cruzi is the etiologic agent of Chagas' disease, a major health problem in Latin America and an emerging infectious disease in the United States. Previously, we screened a T. cruzi sequence database by a computational-bioinformatic approach and identified antigens that exhibited the characteristics of good vaccine candidates. In this study, we tested the vaccine efficacy of three of the putative candidate antigens against T. cruzi infection and disease in a mouse model. C57BL/6 mice vaccinated with T. cruzi G1 (TcG1)-, TcG2-, or TcG4-encoding plasmids and cytokine (interleukin-12 and granulocyte-macrophage colony-stimulating factor) expression plasmids elicited a strong Th1-type antibody response dominated by immunoglobulin G2b (IgG2b)/IgG1 isotypes. The dominant IgG2b/IgG1 antibody response was maintained after a challenge infection and was associated with 50 to 90% control of the acute-phase tissue parasite burden and an almost undetectable level of tissue parasites during the chronic phase, as determined by a sensitive T. cruzi 18S rRNA gene-specific real-time PCR approach. Splenocytes from vaccinated-and-infected mice, compared to unvaccinated-and-infected mice, exhibited decreased (~50% lower) proliferation and gamma interferon (IFN-{gamma}) production when stimulated in vitro with T. cruzi antigens, thus suggesting that protection from challenge infection was not provided by an active T-cell response. Subsequently, the serum and cardiac levels of IFN-{gamma} and tumor necrosis factor alpha and infiltration of inflammatory infiltrate in the heart were decreased in vaccinated mice during the course of infection and chronic disease development. Taken together, these results demonstrate the identification of novel vaccine candidates that provided protection from T. cruzi-induced immunopathology in experimental mice.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, 3.142C Medical Research Building, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1070. Phone: (409) 747-6865. Fax: (409) 747-6869. E-mail: nigarg{at}utmb.edu

{triangledown} Published ahead of print on 11 June 2008.

Clinical and Vaccine Immunology, August 2008, p. 1158-1164, Vol. 15, No. 8
1071-412X/08/$08.00+0     doi:10.1128/CVI.00144-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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