Mucosal Vaccination for Influenza Protection Enhanced by Catalytic Immune‐Adjuvant

Influenza poses a severe threat to global health. Despite the whole inactivated virus (WIV)-based nasal vaccine being a promising strategy for influenza protection, the mucosal barrier is still a bottleneck of the nasal vaccine. Here, a catalytic mucosal adjuvant strategy for an influenza WIV nasal vaccine based on chitosan (CS) functionalized iron oxide nanozyme (IONzyme) is developed. The results reveal that CS-IONzyme increases antigen adhesion to nasal mucosa by 30-fold compared to H1N1 WIV alone. Next, CS-IONzyme facilitates H1N1 WIV to enhance CCL20-driven submucosal dendritic cell (DC) recruitment and transepithelial dendrite(TED) formation for viral uptake via the toll-like receptor(TLR) 2/4-dependent pathway. Moreover, IONzyme with enhanced peroxidase (POD)-like activity by CS modification catalyzes a reactive oxygen species (ROS)-dependent DC maturation, which further enhances the migration of H1N1 WIV-loaded DCs into the draining lymph nodes for antigen presentation. Finally, CS-IONzyme-based nasal vaccine triggers an 8.9-fold increase of IgA-mucosal adaptive immunity in mice, which provides a 100% protection against influenza, while only a 30% protection by H1N1 WIV alone. This work provides an antiviral alternative for designing nasal vaccines based on IONzyme to combat influenza infection.