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