Immunogenicity and protective efficacy of an intranasal neuraminidase-based influenza vaccine with bacterial cell membrane-derived adjuvants.

Development of mucosal influenza virus vaccines which protect the site of viral entry is of high importance. Recombinant neuraminidase (NA) has emerged as an antigenically conserved intranasal vaccine candidate, capable of inducing broad cross-protection, but it requires effective mucosal adjuvants. Here, we analyze the immunogenicity and protective efficacy of a mucosal recombinant NA-based influenza virus vaccine adjuvanted with the outer membrane proteins from Neisseria meningitidis complexed with exogenous lipopolysaccharides (LPS) from Shigella flexneri or endogenous LPS from N. meningitidis. We observed increased follicular T-helper and germinal center B-cell population percentages in nasal-associated lymphoid tissue, enhanced IgA and IgG antibody responses, and accumulation of lung-resident memory T cells. The vaccine provided complete protection against homologous and partial protection against a heterologous influenza virus (clade 2.3.4.4b H5N1) challenge. These findings underscore the potential of bacterial membrane-derived adjuvants for developing robust mucosal influenza vaccines.