Synthetic and natural TLR4 agonists as safe and effective vaccine adjuvants.

Natural derivatives and synthetic analogues of lipopolysaccharide are potent stimulators of the mammalian immune system. Retained adjuvant activity with reduced toxicity was obtained by the development of monophosphoryl lipid A (MPL((R))), which is approved for use in several vaccine products. Ongoing research and development of synthetic TLR4 agonists may offer increased purity and biological activity with reduced cost. Extensive research has elucidated the mechanism of action of TLR4 agonists and structure-function relationships. Moreover, the formulation of TLR4 agonists has been shown to significantly affect the type and magnitude of elicited immune response. TLR4 agonists comprise a promising class of adjuvants for safe and effective vaccines.