Development and evaluation of mosaic VLPs vaccine for enhanced broad-Spectrum immunity against influenza B virus lineages in mice

Influenza B virus (IBV) causes annual respiratory outbreaks, posing significant public health challenges. Traditional vaccines are limited in their effectiveness by antigenic drift and strain mismatches. This study introduces innovative mosaic virus-like particle (VLP) vaccines designed to present a broader range of epitopes, aiming for broad-spectrum immunity against both B/Victoria (BV) and B/Yamagata (BY) IBV lineages in mice. Two mosaic hemagglutinin (HAM) proteins were incorporated into VLPs, mimicking the morphology and size of the virus. Notably, the BV component of our mosaic VLPs demonstrated significant cross-reactivity against the BY strain, surpassing a commercial quadrivalent inactivated influenza vaccine (QIV) in generating broad immune responses. Immunogenicity and efficacy assessments in mice revealed that the mosaic VLPs induced Th1/Th2 cytokine responses and provided effective protection against homologous IBV challenge, notably reducing lung damage. This study highlights the potential of mosaic VLPs in universal influenza B vaccine development and emphasizes the importance of T cell immunity in influenza vaccine design.