CD8+ T-cell responses are the goal of vaccines against intracellular pathogens, such as HIV and malaria, as well as tumours. But, the vaccines and adjuvants that are currently in use work by inducing neutralizing antibodies and are poor stimulators of cellular immunity. Now, a study in the Journal of Experimental Medicine shows that α-galactosylceramide (α-GalCer), a glycolipid that was purified originally from a sea sponge, can be used with vaccines to promote protective T-cell responses.

Natural killer T cells (NKT cells) recognize α-GalCer in the context of the MHC-class-I-like molecule CD1. Although the number of NKT cells is small, they can produce large amounts of interleukin-4 (IL-4) or interferon-γ (IFN-γ) — cytokines that promote humoural or cellular immunity, respectively. Here, the authors tested whether α-GalCer could enhance antimalaria vaccines.

Irradiated malaria sporozoites and recombinant viruses that encode malaria antigens induce protective immunity and good CD8+ T-cell responses in a mouse model. In this study, mice were immunized with suboptimal doses of these vaccines with or without α-GalCer, then challenged with malaria. Strikingly, parasitaemia was ∼10-fold lower in mice that received vaccine plus α-GalCer compared with those given the vaccine alone.

But, which branch of the immune response was enhanced? The authors compared the number of antigen-specific T cells and they found that α-GalCer induces up to a tenfold increase in the number of IFN-γ-producing CD8+ T cells and a less pronounced increase in the number of CD4+ T cells that produce IFN-γ. There was no increase in the number of (IL-4-producing T cells or in antibody responses, and the immunomodulatory effects of α-GalCer were lost in mice deficient for the IFN-γ receptor, which confirms that IFN-γ mediates the adjuvant effects of α-GalCer.

Because α-GalCer activates human NKT cells also, it might prove to be a useful adjuvant for vaccines against malaria and other infections for which IFN-γ-mediated T-cell responses are protective.