Adjuvant potential of archaeal synthetic glycolipid mimetics critically depends on the glyco head group structure.
Subunit vaccines capable of providing protective immunity against the intracellular pathogens and cancers that kill millions of people annually require an adjuvant capable of directing a sufficiently potent cytotoxic T lymphocyte response to purified antigens, without toxicity issues. Archaeosome lipid vesicles, prepared from isoprenoid lipids extracted from archaea, are one such adjuvant in development. Here, the stability of an archaeal core lipid 2,3-di-O-phytanyl-sn-glycerol (archaeol) is used to advantage to synthesize a series of disaccharide archaeols and show that subtle variations in the carbohydrate head group alters the type and potency of immune responses mounted in a mammal. Critically, a glycosylarchaeol was required to elicit high cytotoxic CD8(+) T cell activity, with highest responses to the antigen entrapped in archaeosomes containing disaccharides of glucose in beta- or alpha1-6 linkage (beta-gentiobiose, beta-isomaltose), or of beta-lactose. This first study on synthetic archaeal lipid adjuvants reveals potential for this class of regulatory friendly, easily scalable, inexpensive, and potent glyco-adjuvant.
Sprott
G Dennis
GD
National Research Council of Canada, Institute for Biological Sciences, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada. dennis.sprott@nrc-cnrc.gc.ca
Dicaire
Chantal J
CJ
Côté
Jean-Philippe
JP
Whitfield
Dennis M
DM
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004187:Disaccharides / Q000138:chemical synthesis / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D005995:Glyceryl Ethers / Q000138:chemical synthesis / Q000276:immunology* / Q000494:pharmacology; D006017:Glycolipids / Q000737:chemistry*; D019617:Halobacterium salinarum / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry
D000276:Adjuvants, Immunologic; D004187:Disaccharides; D005995:Glyceryl Ethers; D006017:Glycolipids; C094417:archaeol lipid