cx-Galactosylceramides and analogues - important immunomodulators for use as vaccine adjuvants

A vaccine adjuvant is a substance that is added to improve the effectiveness of a vaccine. Adjuvants are immune potentiators that can elicit an early innate immune response to help in the generation of strong and long-term protection against infection. The adjuvant can enhance the immune system so that less vaccine is required.! The development of a specific immune response (humoral or cell-mediated) can also be determined by the choice of the adjuvant. ex-Galactosylceramides are a family of molecules that have been of particular interest over the past few years due to their significant immunomodulating properties. They and their analogues have displayed adjuvant activity2-5 and have been successful in enhancing the immune response of both live recombinant vaccines and inactivated vaccines against a wide range of diseases including malaria,6 HIV/ viral infection and tumours.s Mice immunized with proteins and ex-galactosylceramides develop antibody titers 1-2 logs higher than those induced by proteins alone. Also, single intranasal administration of ex-galactosylceramides with inactivated influenza virus has resulted in long-term protection. ex-Galactosylceramides stimulate the immune system by a distinct mechanism, they function by stimulating cytokine release of Natural Killer T (NKT) cells that in turn activates the adaptive immune response. Recently, it has been shown that NKT cells can modulate dendritic cells (DCs) and B-cell activity, and can increase DC-induced Band T-cell responses. Activation of NKT cells by ex-galactosylceramides can therefore elicit higher frequencies of memory B cells and higher antibody responses to boost immunizations. -!6 As such, extensive research has been carried out to gain an understanding of ex-galactosylceramides, of their structure, mechanism of action and the reason for their potency. The following review is a summary of the literature that has been published on ex-galactosylceramides, reporting on the developments in their chemical synthesis, on the alterations of the original structure and on the resulting bioactivity of these molecules.