Document Type

Poster

Date of Original Version

3-27-2026

Abstract

The ectodomain of matrix protein 2 (M2e) is highly conserved among influenza A viruses and represents an attractive target for universal influenza vaccines. Because M2e is weakly immunogenic, highly immunogenic platforms are needed to elicit protective responses. We recently developed a flagellin-displayed hepatitis B core (HBc) virus-like particle (VLP) vaccine (FH-M2e VLPs) in which the surface-exposed D3 domain of FljB was replaced with four tandem M2e copies from human H1/H3, swine H1, and avian H5/H7 strains. FH-M2e VLPs induced high anti-M2e IgG and conferred cross-protection in mice; however, they also elicited substantial anti-FljB (anti-flagellin) antibodies. We hypothesized that removing the remaining surface-exposed D2 domain would focus responses on M2e. To test this, we generated D2/D3-deleted FH-M2e VLPs (DFH-M2e VLPs) and compared immunogenicity with FH-M2e VLPs in a murine model. DFH-M2e VLPs maintained strong anti-M2e antibody titers and cross-protective efficacy while reducing anti-flagellin antibody production relative to FH-M2e VLPs. These data support domain-deletion engineering of the flagellin scaffold as a practical strategy to concentrate humoral responses on conserved influenza epitopes while minimizing off-target anti-carrier immunity.

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