Flagellin-Displayed HBc virus-like particles for hemagglutinin Stem-Based Universal Influenza Vaccine Development

Influenza vaccination faces challenges due to viral mutagenicity, necessitating a shift towards universal vaccine approaches. Many current vaccinations target the globular head region of the hemagglutinin (HA) surface protein of the Influenza virus. However, despite the widespread use of this technique, it does not offer broad protection against possible mutations or variations that naturally occur in the Influenza virus. Our study focuses on creating a broadly effective influenza vaccine by targeting the conserved hemagglutinin stem using virus-like particles (VLPs). Through innovative Spy Catcher/Spy Tag technology, we engineered VLPs presenting the HA stem on their surface adjuvanted with the VLP composition containing the Hepatitis B core protein and Flagellin, enhancing immunogenicity. The virus-like particle is made up of two components. The first component is the core of the particle, in which the HBc-flagellin particle assembles into a spherical particle, displaying the Spy Catcher protein on the surface of this particle. This is then combined in solution with a custom HA stem peptide, conjugated with Spy Tag to complete the VLP, with the HA stem displayed on the surface. Preliminary results demonstrating the successful assembly of VLPs into spherical particles visualized by transmission electron microscopyproved the remaining ability of Spy Tag binding to the virus core, and completed gene cloning for the HA stem protein. This project offers insights into universal vaccine design and holds promise for advancing influenza prevention strategies, as well as a theoretical platform for other virus-like particle vaccines.