Cross-Protection Induced by Virus-like Particles Derived from the Influenza B Virus

The mismatch between the circulating influenza B virus (IBV) and the vaccine strain contributes to the rapid emergence of IBV infection cases throughout the globe, which necessitates the development of effective vaccines conferring broad protection. Here, we generated influenza B virus-like particle (VLP) vaccines expressing hemagglutinin, neuraminidase, or both antigens derived from the influenza B virus (B/Washington/02/2019 (B/Victoria lineage)-like virus, B/Phuket/3073/2013 (B/Yamagata lineage)-like virus. We found that irrespective of the derived antigen lineage, immunizing mice with the IBV VLPs significantly reduced lung viral loads, minimized bodyweight loss, and ensured 100% survival upon Victoria lineage virus B/Colorado/06/2017 challenge infection. These results were closely correlated with the vaccine-induced antibody responses and HI titer in sera, IgG, IgA antibody responses, CD4+ and CD8+ T cell responses, germinal center B cell responses, and inflammatory cytokine responses in the lungs. We conclude that hemagglutinin, neuraminidase, or both antigen-expressing VLPs derived from these influenza B viruses that were circulating during the 2020/21 season provide cross-protections against mismatched Victoria lineage virus (B/Colorado/06/2017) challenge infections.