The success of toll-like receptor 4 based vaccine adjuvants

Since the early 1990s, vaccinologists have worked to use adjuvants targeting toll-like receptors in the development of new vaccines. At the forefront of these efforts is the progress made with the toll-like receptor 4 agonist monophosphoryl lipid A which has now been incorporated into different adjuvant systems. These have led to the first vaccines against malaria and respiratory syncytial virus, and improved vaccines for hepatitis B, human papilloma virus, and shingles. In addition to monophosphoryl lipid A, next-generation toll-like receptor 4 adjuvants are under development with potential improvements in manufacturing, efficacy, and tolerability. This review provides a summary of the field of toll-like receptor 4 vaccine adjuvants to date, highlighting their considerable success and the new adjuvants currently under development.