The Journal of Experimental Medicine
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Published 4 March 2002. doi:10.1084/jem.20011889
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© Rockefeller University Press, 0022-1007/2002/3/617/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 5, March 4, 2002 617-624

Original Article

Natural Killer T Cell Ligand {alpha}-Galactosylceramide Enhances Protective Immunity Induced by Malaria Vaccines

Gloria Gonzalez-Aseguinolaza1, Luc Van Kaer2, Cornelia C. Bergmann3, James M. Wilson4, John Schmieg1, Mitchell Kronenberg5, Toshinori Nakayama6, Masaru Taniguchi6, Yasuhiko Koezuka7 and Moriya Tsuji1

1 Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010
2 Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
3 Department of Neurology, University of Southern California, Los Angeles, CA 90033
4 Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia, PA 19104
5 Division of Developmental Immunology, La Jolla Institute of Allergy and Immunology, San Diego, CA 92121
6 Department of MolecularImmunology, Chiba University School of Medicine, Chiba 260, Japan
7 Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma 370, Japan

Address correspondence to Dr. Moriya Tsuji, Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010. Phone: 212-263-6758; Fax: 212-263-8116; E-mail: moriya.tsuji{at}med.nyu.edu

The important role played by CD8+ T lymphocytes in the control of parasitic and viral infections, as well as tumor development, has raised the need for the development of adjuvants capable of enhancing cell-mediated immunity. It is well established that protective immunity against liver stages of malaria parasites is primarily mediated by CD8+ T cells in mice. Activation of natural killer T (NKT) cells by the glycolipid ligand, {alpha}-galactosylceramide ({alpha}-GalCer), causes bystander activation of NK, B, CD4+, and CD8+ T cells. Our study shows that coadministration of {alpha}-GalCer with suboptimal doses of irradiated sporozoites or recombinant viruses expressing a malaria antigen greatly enhances the level of protective anti-malaria immunity in mice. We also show that coadministration of {alpha}-GalCer with various different immunogens strongly enhances antigen-specific CD8+ T cell responses, and to a lesser degree, Th1-type responses. The adjuvant effects of {alpha}-GalCer require CD1d molecules, V{alpha}14 NKT cells, and interferon {gamma}. As {alpha}-GalCer stimulates both human and murine NKT cells, these findings should contribute to the design of more effective vaccines against malaria and other intracellular pathogens, as well as tumors.

Key Words: {alpha}-galactosylceramide • NKT cells • adjuvant • malaria vaccines • CD8+ T cells


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