Innate immune function in higher organisms involves recognition of molecular patterns found in pathogenic organisms.  These patterns include glycolipids from bacteria, fungi, and parasites, and in mammals the recognition process includes presentation of glycolipids to a subset of T cells, termed natural killer T (NKT cells).  Upon recognition of specific molecular patterns in glycolipids, NKT cells are activated, release cytokines, and interact with other cells in the immune system.  As the patterns recognized by NKT cells are better understood, their immune regulatory functions can be harnessed to provide specific immune responses, including immunostimulation programmed to potentiate the effectiveness of vaccines.  Our research, along with that from other groups, has resulted in the identification of molecular patterns recognized by NKT cells.  Through structure-activity studies, the immunostimulatory properties of glycolipids have been optimized, and we are using a lead glycolipid to improve responses to vaccines.  A key aspect of this effort involves efforts to improve carbohydrate vaccines.  Typically, carbohydrate epitopes are attached to a protein or a peptide in a multivalent array, and protective antibody responses often require repeated vaccinations.  We have generated monomeric, protein/peptide-free, carbohydrate vaccines that self assemble, with an NKT cell antigen, into liposomes to provide the necessary multivalency and NKT cell stimulation.  Vaccination with the liposomes results in generation of high titers of high-affinity antibodies (IgG) for the targeted carbohydrates with a single vaccination.

Harnessing the immunostimulatory properties of glycolipids for vaccine development

247th National Meeting (2014)

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