H5N1 influenza virus-like particles based on BEVS induce robust functional antibodies and immune responses

Avian influenza virus infections pose a potential pandemic threat. The currently licensed vaccines have inherent limitations, emphasizing the urgent need for improved influenza vaccines. Here, we developed a novel hemagglutinin (HA) virus-like particle (VLP) vaccine candidate through the baculovirus expression vector system (BEVS). The engineered VLPs incorporate HA from H5N1 and matrix 1 (M1) protein from H1N1. Comprehensive characterization revealed that purified HA VLPs exhibited morphological fidelity to native influenza virions while maintaining key viral biological properties. Immunization studies in murine models demonstrated the superior immunogenicity of HA VLPs through a prime-boost regimen. Compared to control groups receiving HA monomer or T4-foldon-trimerized HA formulations, VLP-immunized mice showed significantly enhanced humoral responses and robust cellular immunity. This study provides compelling evidence for advancing VLP-based vaccines as a superior alternative to conventional influenza vaccine formulations.