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Glycobiology Advance Access published online on May 1, 2008
Glycobiology, doi:10.1093/glycob/cwn038
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Adjuvant potential of archaeal synthetic glycolipid mimetics critically depend on glyco head group structure

G.D. Sprott1,3, C.J. Dicaire1, J.-P. Côté1,2 and D.M. Whitfield1

1 National Research Council of Canada, Institute for Biological Sciences, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada

3 To whom correspondence should be addressed: Tel: +1-613-998-7891; Fax: +1-613-952-9092; e-mail: dennis.sprott{at}nrc-cnrc.gc.ca.

Received on February 28, 2008; accepted on April 28, 2008

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 antigen entrapped in archaeosomes containing disaccharides of glucose in β or {alpha} 1–6 linkage (β-gentiobiose, β-isomaltose), or of β-lactose. This first study on synthetic archaeal lipid adjuvants reveals potential for this class of regulatory friendly, easily scalable, inexpensive and potent glyco-adjuvant.

Key words: adjuvant / archaea / disaccharides / glycosylarchaeols / synthesis

2 Current address: Université de Montréal, Faculté de Médecine Vétérinaire, St.-Hyacinthe, 3200 Sicotte, St.-Hyacinthe, Québec J2S 7C6, Canada


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[Abstract] [Full Text] [PDF]


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