Novel Mini‐Hemagglutinin Subunit Vaccine Induces Robust Mucosal and Systemic Immunity and Protection Against a Lethal Challenge With the H1N1 and H5N1 Influenza Viruses in Mice

Conventional influenza vaccines target the globular head domains of hemagglutinins (HAs), which are highly plastic and provide strain-specific immunity. Therefore, a universal influenza vaccine with conserved antigens and novel adjuvants is urgently required. Mucosal immunity is the first line of defense against viral infections; however, proven mucosal adjuvants are lacking. Therefore, we developed an intranasal Mini-HA subunit vaccine combined with the CTA1-DD adjuvant, which elicited robust mucosal and systemic immune responses in the lungs and spleens of mice, including antigen-specific IgA, IgG, and effector T cells. Furthermore, the Mini-HA subunit vaccine provided the mice with cross-protection against H1N1 and H5N1 influenza viruses. These results indicate that combining the Mini-HA antigen and mucosal adjuvant CTA1-DD is a promising strategy for developing broad-spectrum influenza vaccines.