Nanoadjuvant and recombinant hemagglutinin protein-based mucosal influenza nanovaccine confers protection against lethal viral challenge in mice

Influenza virus poses a constant pandemic threat and global health challenge. As the first line of defense at the virus entry portal, mucosal immunity is essential to provide cross-protection against influenza virus. Hemagglutinin (HA), a major influenza virus antigen, could not penetrate the nasal barriers and is prone to removal by mucociliary clearance when nasally administered alone. Appropriate mucosal adjuvants and delivery systems were necessitated to induce the mucosal immunity. In this study, a novel mucosal nanovaccine (rHA-GEP-cG) was prepared by assembly of HA with β glucan, polypeptide EEEEEEEEC, PAMAM dendrimer, and 2',3'-cGAMP. Intranasal administration of rHA-GEP-cG induced robust mucosal, systemic humoral and cellular immune responses, including secretion of IFN-γ, IL-4 and IL-17A. High levels of rHA specific IgG and IgA were detected in the mouse sera and the respiratory tract, along with long-term cross-reactive immune response in murine models. In addition, rHA GEP-cG provided partial cross-protection against lethal challenges with heterosubtypic H1N1 and H5N1 in BALB/c mice. This mucosal nanovaccine represents a promising approach for influenza vaccine development and could help mitigate seasonal or pandemic influenza outbreaks.