iNKT cell agonists as vaccine adjuvants to combat infectious diseases.

iNKT cells are a special type of T cell that acts as a link between the innate and adaptive immune systems, with the capacity to stimulate a wide range of cell types. The glycolipid α-galactosylceramide (αGC) is a robust agonist of iNKT cells and induces the secretion of Th1- and Th2-type cytokines. αGC and its analogs are widely used as adjuvants to enhance immune responses against viral, parasitic, and bacterial pathogens. This review first discusses the challenges of using free αGC as a vaccine adjuvant to treat infectious diseases. We next present strategies to realize the potential of the adjuvant effect of iNKT cell glycolipids, including (1) the use of Th1- or Th2-biasing αGC analogs, (2) covalent conjugation of glycolipid with antigen, (3) particulate vehicle-assisted delivery of glycolipid, (4) glycolipid-loaded cellular systems, (5) glycolipid combination with other immunostimulants, and (6) usage as mucosal adjuvants. Finally, we discuss future approaches for the development of iNKT cell agonists used as vaccine adjuvants against infectious diseases.