Natural killer T cell ligand α-galactosylceramide enhances protective immunity induced by malaria vaccines

G Gonzalez-Aseguinolaza, L Van Kaer… - The Journal of …, 2002 - rupress.org
G Gonzalez-Aseguinolaza, L Van Kaer, CC Bergmann, JM Wilson, J Schmieg…
The Journal of experimental medicine, 2002rupress.org
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, α-galactosylceramide
(α-GalCer), causes bystander activation of NK, B, CD4+, and CD8+ T cells. Our study shows …
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, α-galactosylceramide (α-GalCer), causes bystander activation of NK, B, CD4+, and CD8+ T cells. Our study shows that coadministration of α-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 α-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 α-GalCer require CD1d molecules, Vα14 NKT cells, and interferon γ. As α-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.
rupress.org