Bacterial Glycolipid Lipid As and Their Potential as Adjuvants

Lipopolysaccharide (LPS), the major glycoconjugate in the outer membrane of Gram-negative bacteria, and its active principle glycolipid, lipid A, are recognized by Toll-like receptor (TLR) 4, trigger immunostimulatory effects, and thus have the potential to act as vaccine adjuvants. Canonical Escherichia coli LPS causes strong inflammation and hypersensitizes the immune system, thus acting as an endotoxin, but recent studies have shown that structural modification of lipid A can attenuate its toxicity. In this chapter, the structure–activity relationship of lipid A and its potential as a vaccine adjuvant are discussed. A strategy to develop gut-associated lymphoid tissues using bacterial lipid A as a safe lipid A adjuvant based on bacterial–host chemical ecology is introduced. Self-adjuvanting strategy to enhance the adjuvant function of lipid A is also presented.