Rational design of adjuvants targeting the C-type lectin Mincle

Significance For many years, the development of adjuvants—compounds that boost the immunogenicity of vaccines—has been an empirical process. Adjuvants inducing a strong humoral immunity are available, but adjuvants directing the development of robust cellular immune responses are still needed. Recently, the C-type lectin receptor Mincle was found to elicit such responses on the recognition of microbial glycolipids, thereby providing a basis for the rational design of new adjuvants. Here we used a multidisciplinary approach, combining chemical synthesis, biology, and molecular modeling to decipher the molecular bases of ligand recognition by the receptor. This led us to synthesize new compounds inducing stronger immune responses than the currently available Mincle ligands that represent new powerful adjuvant molecules.