Immunogenicity and protection of octavalent influenza vaccine candidates using adjuvanted proteins or mRNA-LNPs in naïve mice

Currently used influenza vaccines primarily induce antibody responses against hemagglutinin (HA). Neuraminidase (NA) has been proposed as a complementary antigen to improve and potentially expand the breadth of influenza vaccine protection. Here, we assessed the immunogenicity and protective potential of adjuvanted recombinant protein- and mRNA-LNP-based octavalent influenza vaccine formulations in naïve mice. The vaccine candidates contained HA and NA derived from the viruses recommended for the 2018-2019 Northern Hemisphere quadrivalent influenza vaccine. Both adjuvanted recombinant protein and mRNA-LNP formats fully protected mice against challenge with homologous H1N1, influenza B, and HxN2 viruses. However, the octavalent mRNA-LNP vaccine elicited higher serum IgG titers against both HA and NA compared with the adjuvanted octavalent recombinant protein vaccine in this animal model. Furthermore, the octavalent mRNA-LNP vaccine also protected mice against challenge with the historical H3N2 virus strains X31, X47, and X79. This protection correlated with the presence of HA cross-reactive serum antibodies and was confirmed by passive transfer of immune serum into unvaccinated mice.