| dc.description.abstract | Seasonal influenza viruses pose a significant threat to global health, necessitating effective
prevention strategies. While vaccination remains the cornerstone, current methods primarily rely
on inactivated split virus vaccines generated using embryonated chicken eggs (ECE), present
various drawbacks including allergic reactions, adaptive mutation in hemagglutinin (HA) gene,
disruptions in egg supply, and scalability issues. To overcome the dependency on ECE,
developments of influenza vaccines based on efficient and robust production platforms are urgently
needed. Several potential vaccine production systems have shown potential as replacers, including
a virus-like particle (VLP) platform. In this study, using a Baculovirus Expression System (BES),
we engineered HA, NA, and M1 genes of influenza A/H1N1, A/H3N2, B/Yamagata-like, and
B/Victoria-like virus strains (A/Hawaii/70/2019, A/Minnesota/41/2019, B/Brisbane/09/2014 &
B/Brisbane/63/2014) to produce VLP vaccine antigens H1N1-VLP, H3N2-VLP, Yamagata-VLP,
Victoria-VLP, respectively. We then assessed their functional and antigenic characteristics,
including hemagglutination assay, protein composition, HA protein productivity, VLPs
morphology, stability and immunogenicity. We found that recombinant VLPs displayed functional
activity, resembling influenza virions in morphology and size, while maintaining structural
integrity. Comparative immunogenicity assessments in mice showed that our quadrivalent VLPs
were consistent in inducing hemagglutination inhibition (HAI) and neutralizing (NT) antibody
titers against homologous viruses compared to both commercial recombinant HA (Flublok) and
egg-based vaccines (Vaxigrip). Since the HA antigen yields of the homologous VLPs varied more
than four folds, we further developed chimeric VLPs to improve HA protein production and
address the limitations of the homologous VLPs. We assessed their antigenic characteristics,
comparative HA protein productivity, immunogenicity and vaccine efficacy. We found that similar
to homologous VLPs, chimeric VLPs displayed functional activity, resembling influenza virions
in morphology and size. Comparative immunogenicity assessments in mice showed that the VLP
vaccine consistent in inducing higher hemagglutination inhibition and neutralizing antibody titers
and provided 100% protection against homologous viruses compared to the commercial vaccine.
The findings highlight insect cell-based VLP vaccines as promising candidates for quadrivalent
seasonal influenza vaccines. | en_US |