Old and new adjuvants

•Insoluble aluminum salts have long been used to stimulate B and CD4 T cell responses.•The need for IL-1/MyD88 for alum's adjuvancy depends on the site of administration.•Squalene's enhancement of immunity depends on MyD88 and germinal centers.•TLR agonists with alum, liposomes or emulsions increase antibody and cellular immunity.

Adjuvants have been deliberately added to vaccines since the 1920's when alum was discovered to boost antibody responses, leading to better protection. The first adjuvants were discovered by accident and were used in the safer but less immunogenic subunit vaccines, supposedly by providing an antigen depot to extend antigen presentation. Since that time, much has been discovered about how these adjuvants impact cells at the tissue site to activate innate immune responses, mobilize dendritic cells and drive adaptive immunity. New approaches to vaccine construction for infectious diseases that have so far not been well addressed by conventional vaccines often attempt to induce antibodies, polyfunctional CD4+ T cells and CD8+ CTLs. The discovery of pattern recognition receptors and ligands that drive desired T cell responses has led to development of novel adjuvant strategies using immunomodulatory agents to direct appropriate immune responses.