Innovations in formulation and delivery systems for TLR7/8 agonists. Innovations in formulation and delivery systems for TLR7/8 agonists. Small molecule TLR 7/8 agonists have demonstrated great potential as vaccine adjuvants because they directly activate APCs and can enhance both humoral and cellular immune responses, especially Th1 responses. The most promising innovations in formulation and use of delivery systems for TLR7/8 agonists include 1) lipidation approaches, as best demonstrated by 3M-052, a TLR7/8-activating IMQ bearing a C18 lipid moiety and designed for slow dissemination from the site of injection, 2) encapsulating nanoparticles (e.g., polymersomes), 3) adsorption to alum adjuvants (TLR7 agonists are functionalized with polyethylene glycol linkers), in which terminal phosphonate groups allow for ligand exchange of hydroxyl and/or phosphate groups on the surface of aluminum hydroxide [Al(OH)3] or phosphate (AlPO4), 4) conjugation to polymers and/or protein Ags, and 5) additive/synergistic admixture combinations with other adjuvants such as TLR4 adjuvants. David J. Dowling ImmunoHorizons 2018;2:185-197 Copyright © 2018 The Authors