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Protection of Susceptible BALB/c Mice from Challenge with Leishmania major by Nucleoside Hydrolase, a Soluble Exo-antigen of Leishmania

Leishmania major culture-derived, soluble, exogenous antigens have been shown to be a source of vaccine targets for the parasite. We have previously reported that L. major culture-derived, soluble, exogenous antigens can immunize BALB/c mice against challenge with L. major. However, the molecule(s) involved in this protection was not known. We describe the potential of one component of soluble exogenous antigens (recombinant nucleoside hydrolase) to vaccinate mice against challenge with L. major. We found that recombinant nucleoside hydrolase vaccinated BALB/c mice against a subsequent challenge with L. major. Protection was manifested by a significant decrease in lesion size (as much as a 30-fold reduction) and parasite burden (as much as a 71-fold reduction). Protection was achieved whether recombinant nucleoside hydrolase was administered to mice in the presence or absence of adjuvant (interleukin-12). Finally, protection was accompanied by an increase in interferon- production but a decrease in interleukin-10 production by vaccinated animals in response to challenge with L. major.

Received June 26, 2007. Accepted for publication August 22, 2007.

Acknowledgments: We thank Jeremy Jones, Leanna Nobisch, and Jeanette Bishop for expert technical assistance.

Financial support: This study was supported in part by the Medical Research and Materiel Command, Military Infectious Diseases Research Program, contract number DAMD17-01-P-0237 and National Institutes of Health grants AI 27511, AI 29955, and AI 065784. Mohammad A. Al-Wabel was supported by a scholarship from Qassim University (Buraydah, Al-Qaseem, Saudi Arabia).

^* Address correspondence to Richard G. Titus, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1619 Campus Delivery, Fort Collins, CO 80523-1619. E-mail: richard.titus{at}colostate.edu

Authors’ addresses: Mohammad A. Al-Wabel and Richard G. Titus, Department of Microbiology Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1619 Campus Delivery, Fort Collins, CO 80523-1619, E-mails: malwabel{at}lamar.colostate.edu and richard.titus{at}colostate.edu. Willy K. Tonui, Centre for Biotechnology Research and Development, Kenya Medical Research Institute, Mbagathi Way, PO Box 54840-00200, Nairobi, Kenya, E-mail: wtonui{at}kemri.org. Liwang Cui, Department of Entomology, College of Agricultural Sciences, 537 ASI, Pennsylvania State University, University Park, PA 16802, E-mail: luc2{at}psu.edu. Samuel K. Martin, United States Army Medical Research Unit-Kenya, Unit 64109, APO AE 09831-4109, Nairobi, Kenya, E-mail: Smartin{at}wrp.nbo.org.