Natural killer T cell ligand alpha-galactosylceramide enhances protective immunity induced by malaria vaccines.
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, Valpha14 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.
Gonzalez-Aseguinolaza
Gloria
G
Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010, USA.
Van Kaer
Luc
L
Bergmann
Cornelia C
CC
Wilson
James M
JM
Schmieg
John
J
Kronenberg
Mitchell
M
Nakayama
Toshinori
T
Taniguchi
Masaru
M
Koezuka
Yasuhiko
Y
Tsuji
Moriya
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D018949:Antigens, CD1 / Q000502:physiology; D055610:Antigens, CD1d; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005699:Galactosylceramides / Q000494:pharmacology*; D007371:Interferon-gamma / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D005699:Galactosylceramides; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma