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Immunolocalization and Challenge Studies Using a Recombinant Vibrio cholerae Ghost Expressing Trypanosoma brucei Ca²⁺ ATPase (TBCA2) Antigen

Human African trypanosomiasis is a neglected disease caused by Trypanosoma brucei spp. A parasite cation pump (Ca²⁺ ATPase; TBCA2) essential for survival and cation homeostasis was identified and characterized. It was hypothesized that targeting this pump using a Vibrio cholerae ghost (VCG)-based vaccine could protect against murine T. brucei infection. mRNA and protein expression of TBCA2 was differentially expressed in blood and insect stages of parasites and immunolocalized in the pericellular membrane and the flagellar pocket of bloodstream forms. Antigen-specific antibodies and Th1 cytokines, interleukin-2, interferon-gamma, and tumor necrosis factor-alpha were induced in rVCG-TBCA2-immunized mice and in vitro on antigen stimulation of splenic immune T cells, but the corresponding Th2-type response was unremarkable. Despite an increased median survival of 6 days in vaccinated mice, the mice were not protected against infection. Thus, immunization of mice produced robust parasite-specific antibodies but failed to protect mice against parasite challenge.

Received January 25, 2008. Accepted for publication May 23, 2009.

Acknowledgment: The authors thank Dorothea Parker of Morehouse School of Medicine for the production of TBCA2 monoclonal antibodies.

Financial support: This study was conducted in a facility constructed with support from Research Facilities Improvement Program Grant 1 C06 RR18386 from the National Center for Research Resources, National Institutes of Health. This work was supported by grants from NIH-NIGMS-MBRS (SO6GM08248) and NIH-RCMI (RR03034).

^* Address correspondence to Jonathan K. Stiles, Morehouse School of Medicine, Department of Microbiology, Biochemistry, and Immunology, BMSB Room 349D, 720 Westview Drive SW, Atlanta, GA 30310. E-mail: jstiles{at}msm.edu

Authors’ addresses: Kiantra Ramey, Morehouse School of Medicine, Department of Microbiology, Biochemistry, and Immunology, BMSB Room 350, 720 Westview Drive SW, Atlanta, GA 30310, Tel: 404-752-1765, Fax: 404-752-1179, E-mail: kramey{at}msm.edu. Francis O. Eko, Morehouse School of Medicine, Department of Microbiology, Biochemistry, and Immunology, BMSB Room 333, 720 Westview Drive SW, Atlanta, GA 30310, Tel: 404-752-1584, Fax: 404-752-1179, E-mail: feko{at}msm.edu. Winston E. Thompson, Morehouse School of Medicine, Department of Obstetrics and Gynecology and Cooperative Reproductive Science Research Center, 720 Westview Drive SW, Atlanta, GA 30310, Tel: 404-752-1715, E-mail: wthomp-son{at}msm.edu. Henry Armah, University of Pittsburgh Medical Center, Department of Pathology, A711 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, Tel: 412-647-5550, Fax: 412-802-6079, E-mail: armahh2{at}upmc.edu. Joseph U. Igietseme, Centers for Disease Control and Prevention, National Centers for Infectious Diseases/ Scientific Resources Program, Mail Stop C17, 1600 Clifton Road, Atlanta, GA 30333, Tel: 404-639-3352, E-mail: jbi8{at}cdc.gov. Jonathan K. Stiles, Morehouse School of Medicine, Department of Microbiology, Biochemistry, and Immunology, BMSB Room 349D, 720 Westview Drive SW, Atlanta, GA 30310, Tel: 404-752-1585, Fax: 404-752-1179, E-mail: jstiles{at}msm.edu.