Flagellin as a Versatile Adjuvant Platform: Genetic Fusion Approaches for Next-Generation Vaccines

Flagellin is the main structural protein of the bacterial flagellum, responsible for the movement of flagellated bacteria. Flagellin activates Toll-like receptor 5, inducing both innate and adaptive immune reactions, which highlights its potential as a vaccine adjuvant, particularly efficient in case of administration via mucosal routes. Genetic fusion of an antigen to flagellin has been shown to enhance the immune responses against the antigen. The molecular architecture of flagellin provides versatile and robust adjuvant functionality, facilitating the development of diverse vaccination strategies against multiple diseases as recombinant protein-based vaccines demonstrate substantial advantages over conventional live-attenuated and inactivated vaccines in both developmental efficiency and safety profiles. We present a comprehensive overview of vaccine design strategies employing genetic fusion of antigens to flagellin for protection against various infectious diseases. The proven effectiveness of flagellin-based delivery has enabled several vaccine candidates to enter clinical trials.