Exploration of MAIT cell-activating ligands and their potential as vaccine adjuvants for infectious diseases

Vaccine adjuvants play a critical role in enhancing the magnitude and quality of immune responses; however, limitations in the efficacy of current vaccines against certain infectious diseases, together with the ongoing emergence of new pathogens, underscore the need for the continued development of novel vaccine adjuvants. Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that respond rapidly during the early phase of microbial infection to amplify immune responses and bridge innate and adaptive immunity. Molecules capable of activating MAIT cells therefore have the potential to act as efficacious vaccine adjuvants. This review discusses emerging evidence supporting the potential of MAIT cell activators as vaccine adjuvants. Recent advances in the discovery and development of MAIT cell-activating ligands are summarized, highlighting natural ligands derived from microbial riboflavin metabolism, most notably 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU). Several recent studies have demonstrated 5-OP-RU to be an effective adjuvant in vaccines against viral infections, markedly expanding interest in MAIT cell-targeted immunomodulation. Furthermore, ongoing efforts to overcome the intrinsic chemical instability of 5-OP-RU through rational ligand design and related strategies are described. MAIT cell activators are poised to attract increasing attention as a versatile platform for the design of next-generation vaccine adjuvants against infectious diseases.