Development of a chimeric hemagglutinin-based live-attenuated influenza vaccine against both lineages of influenza B virus

BACKGROUND: The development of a universal influenza vaccine remains a critical goal to enhance protection against diverse influenza virus strains. While vaccines against influenza type A viruses have benefited from the use of chimeric hemagglutinin designs, strategies for influenza type B vaccines still lag. AIM: The study aimed to investigate the efficacy of chimeric vaccine strains to induce humoral immune response targeting conserved antigenic sites of influenza type B virus. METHODS: A chimeric hemagglutinin was engineered by combining the head domain from the B/Brisbane/60/2008 virus (Victoria lineage) with the stalk domain from the B/Phuket/3073/2013 virus (Yamagata lineage). The gene encoding the chimeric hemagglutinin was incorporated into a vaccine virus based on the cold-adapted B/USSR/60/69 master donor virus to produce live-attenuated influenza vaccine. Mice were sequentially vaccinated with the conventional live-attenuated influenza vaccine and then with the recombinant live-attenuated influenza vaccine expressing the chimeric hemagglutinin. Immune responses and cross-protection against both homologous and heterologous influenza type B virus strains were assessed. RESULTS: The engineered chimeric hemagglutinin did not impair the replication or assembly of the vaccine virus. Sequential vaccination induced a robust humoral immune response and provided protection against both homologous and heterologous influenza type B virus strains in the mouse model. CONCLUSION: Live-attenuated influenza type B vaccines expressing chimeric hemagglutinin show promise in broadening protection against influenza type B virus infection. These findings support the development of a universal influenza type B vaccine using a chimeric hemagglutinin design.