Title : Hybrid flagellin-hepatitis b virus-like particle and mRNA-based universal influenza
Abstract:
Ectodomain of matrix protein 2 (M2e) is highly conserved among influenza A viruses and represents an attractive target in universal influenza vaccine development. Due to its low immunogenicity, highly immunogenic vaccine platforms are required to develop effective M2e-based universal influenza vaccines. We recently developed a flagellin-displayed hepatitis B core (HBc) VLP-based M2e vaccine (FH-M2e VLPs), where the surface-exposed D3 domain of FljB was replaced with four tandem copies of M2e originated from human H1/H3, swine H1, and avian H5/H7 viruses. FH-M2e VLPs induced high anti-M2e antibody titers and conferred cross-protection against various influenza A viral challenges in murine models. Yet, we observed significant anti-FljB antibody production. We hypothesized that removal of the surface-exposed D2 domain would allow immune responses to focus on surface-displayed M2e and enhance anti-M2e antibody production. We prepared D2/D3-deleted FH-M2e VLPs (DFH-M2e VLPs) to compare its immunogenicity with FH-M2e VLPs in murine model. Besides VLP platform, mRNA platform has shown high immunogenicity, rapid production, and good safety to support COVID-19 vaccine development and was also used to develop FljB-HBc-based M2e mRNA vaccine. A pilot study found three doses of FljB-HBc-M2e mRNA vaccine at 5µg dose elicited comparable anti-M2e antibody titer to two doses of FH-M2e VLP vaccine. This pilot study hinted the promise of FljB-HBc-M2e mRNA vaccine to elicit potent anti-M2e antibody responses without the time-consuming processes to prepare endo-free FH-M2e VLP vaccines.
