A Redox-Responsive β-Glucan-Based Vaccine Recruiting Endogenous Antibodies to Potentiate Antifungal Immunity.

Invasive fungal infections caused by Candida albicans pose a serious threat to human health, particularly in immunocompromised individuals. Surface-exposed β-glucans of C. albicans have been identified as promising targets for antifungal vaccine development. However, conventional glycoconjugate vaccines often suffer from limited immunogenicity. Herein, we report an innovative vaccine strategy that recruits endogenous antibodies, such as anti-rhamnose (Rha) antibodies, to improve antigen delivery to antigen-presenting cells (APCs). A redox-responsive disulfide linker was incorporated into the vaccine design to promote endosomal escape and enhance antigen processing. The construct was prepared by conjugating β-glucans to bovine serum albumin (BSA), followed by coupling Rha haptens via the redox-responsive linker, yielding β-glucans-BSA-L2-Rha. Immunological evaluations demonstrated that the presence of endogenous anti-Rha antibodies substantially enhanced immune responses, with the redox-responsive glycoconjugate eliciting the strongest reactivity. Moreover, antisera generated by the vaccine effectively recognized the hyphal form of heat-killed C. albicans (HKCA). This study establishes a broadly applicable strategy for the further development of antifungal vaccines.