Adhesive adjuvant protein for long-lasting immune response in vaccination

Subunit vaccines remain essential despite recent advances in mRNA technology, due to their lower pathogenicity risk, targeted immune responses, and superior stability profiles. However, because of their low immunogenicity, effective adjuvants are required to elicit robust, long-lasting immunity comparable to that of natural infections. Conventional adjuvants, such as aluminum (alum), provide only limited cellular activation and rapid antigen clearance, thereby limiting their efficacy. Similarly, potent peptide adjuvants are hampered by short in vivo half-lives. Bioengineered mussel adhesive protein (MAP) has attracted substantial attention for its unique underwater adhesive properties and non-immunogenicity, owing to its intrinsically disordered structural nature. Here, we aim to establish a mussel-inspired adhesive adjuvant protein (AAP) that leverages the underwater adhesiveness of MAP and the immunostimulatory effect of the adjuvant peptide. AAP enables the formation of an in situ crosslinked nanoparticulate vaccine that mimics natural infection dynamics by creating an antigen depot. In vitro and in vivo evaluations confirmed that this formulation significantly prolongs retention of antigen and adjuvant compared with alum, thereby inducing robust, sustained, and balanced immune responses. This study demonstrates that the adhesive adjuvant protein-based nanoparticulate vaccine can elicit potent immune responses and finely modulate immune responses, making it a promising vaccine candidate.