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Infection and Immunity, October 2004, p. 5654-5661, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.5654-5661.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Immunization with Leishmania major Exogenous Antigens Protects Susceptible BALB/c Mice against Challenge Infection with L. major

Willy K. Tonui,1,2 J. Santiago Mejia,1 Lisa Hochberg,3 M. Lamine Mbow,1,4 Jeffrey R. Ryan,3,5 Adeline S. T. Chan,3 Samuel K. Martin,6 and Richard G. Titus1*

Department of Microbiology Immunology and Pathology, Colorado State University, Fort Collins Colorado,1 Centre for Biotechnology Research and Development, Kenya Medical Research Institute, Nairobi,2 United States Army Medical Research Unit, Kenya,6 Department of Entomology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland,3 Centocor, Inc., Malvern, Pennsylvania,4 Cepheid, Sunnyvale, California5

Received 9 April 2004/ Returned for modification 22 May 2004/ Accepted 7 July 2004

The potential of Leishmania major culture-derived soluble exogenous antigens (SEAgs) to induce a protective response in susceptible BALB/c mice challenged with L. major promastigotes was investigated. Groups of BALB/c mice were immunized with L. major SEAgs alone, L. major SEAgs coadministered with either alum (aluminum hydroxide gel) or recombinant murine interleukin-12 (rmIL-12), L. major SEAgs coadministered with both alum and rmIL-12, and L. major SEAgs coadministered with Montanide ISA 720. Importantly and surprisingly, the greatest and most consistent protection against challenge with L. major was seen in mice immunized with L. major SEAgs alone, in the absence of any adjuvant. Mice immunized with L. major SEAgs had significantly smaller lesions that at times contained more than 100-fold fewer parasites. When lymphoid cells from L. major SEAg-immunized mice were stimulated with leishmanial antigen in vitro, they proliferated and secreted a mixed profile of type 1 and type 2 cytokines. Finally, analyses with Western blot analyses and antibodies against three surface-expressed and secreted molecules of L. major (lipophosphoglycan, gp46/M2/PSA-2, and gp63) revealed that two of these molecules are present in L. major SEAgs, lipophosphoglycan and the molecules that associate with it and gp46/M2/PSA-2.

* Corresponding author. Mailing address: Department of Microbiology Immunology and Pathology, CVMBS, Colorado State University, 1619 Campus Delivery, Fort Collins, CO 80523-1619. Phone: (970) 491-1607. Fax: (970) 491-0603. E-mail: richard.titus{at}colostate.edu.

Editor: W. A. Petri, Jr.

Infection and Immunity, October 2004, p. 5654-5661, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.5654-5661.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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