Novel influenza H7N9 virus-like particle vaccines with modified glycosylation sites induce broad-spectrum antibody responses in mice 3561

Description Egg-based platforms have been widely used to produce seasonal influenza vaccines but could not meet surging demand during influenza pandemics. It is desirable to develop alternative platforms which could simultaneously handle different requirements for seasonal and pandemic influenza vaccines. The insect cell-based platform has been applied to produce recombinant subunit vaccines against seasonal influenza but its market share is low (<5%) due to low immunogenicity and high cost. The influenza VLP vaccine could have a better immunogenicity than recombinant subunit vaccines and would be more suitable for pandemic preparedness. Influenza H7N9 viruses emerged through zoonotic transmission in China in 2013 and evolved into three antigenic groups by 2019 with limited cross-protection. A broad-spectrum influenza H7N9 vaccine is critical for pandemic preparedness. Based on sequence alignment of hemagglutinin genes of H7N9 variants, six amino acid mutations including two glycosylation sites in the HA1 region were selected to generate mutant VLPs for identifying the immunodominant sites and selecting vaccine candidates with modified glycosylation. Compared with unmodified VLP vaccine candidates, three mutant VLP vaccine candidates could induce improved cross-reactive hemagglutination inhibition (HI) and neutralizing antibody titers against three antigenic groups in mice. Further animal immunization and challenge studies are warranted.