Mucoadhesive Antioxidant Nanoadjuvant Delivers Enhanced Intranasal Influenza Vaccine Immunogenicity.

Influenza viruses remain a persistent and significant threat to global public health. However, currently available whole inactivated virus (WIV) vaccines fail to elicit robust mucosal immune responses, weakening the first line of defense against respiratory viral infection. Intranasal vaccination represents a promising strategy for achieving both mucosal and systemic immunity against influenza, but safe and highly immunostimulatory adjuvants are required for good efficacy. Here, we developed a multifunctional nanocomposite adjuvant, GO-IONPs-PEI (GIP), which was designed to enhance immunogenicity, regulate inflammatory responses, and maintain local redox homeostasis. Following intranasal coadministration with the influenza antigen, GIP nanoparticles exhibited excellent biocompatibility and effectively promoted dendritic cell maturation, likely via the active modulation of the mucosal immune microenvironment. In vivo, GIP markedly enhanced both systemic and mucosal immune responses, including the robust induction of protective mucosal IgA responses. Collectively, these findings reveal that GIP could be a promising adjuvant platform for next-generation intranasal influenza vaccines. Furthermore, the results highlight that the multifunctional modulation of the mucosal microenvironment is an effective strategy for improving the performance of WIV vaccines.