Toll-like receptors (TLRs) are pattern recognition receptors found on cells of the immune system that stimulate both innate and adaptive immune responses to microbes. Microbial products that target TLRs have been used as the basis for adjuvants that enhance vaccine efficacy. Variants of lipopolysaccharide (LPS), the main cell-surface component of Gram-negative bacteria, are potent stimulators of host defense systems via their interaction with TLR4, but the toxicity of LPS and its active principle, lipid A, have precluded their use as adjuvants. Thus, considerable effort has been directed towards the development of synthetic lipid A mimetics with simplified structures and improved toxicity/activity profiles for use as TLR4-directed vaccine adjuvants and stand-alone immunotherapeutics. To this end, Corixa/GlaxoSmithKline is developing a new class of potent lipid A-like immunomodulators known as aminoalkyl glucosaminide phosphates (AGPs). Several members of this class of lipid A mimetics have been shown to improve humoral and cell-mediated immune responses to a variety of different antigens in mice as well as enhance non-specific resistance (NSR) in mice to viral and bacterial infections.
