Engineered self-assembly of mucoadhesive Helicobacter pylori vaccines: CD4⁺ T cell-dependent immunity prevents...

Helicobacter pylori (H. pylori) infection represents a significant global health burden, being strongly associated with the development of various gastrointestinal pathologies. Immunization emerges as the most promising strategy for population-level prevention. In this study, we described the rational design of a novel multi-antigenic H. pylori vaccine, which was strategically engineered to target key pathogenic mechanisms: gastric acid survival, mucus layer penetration, epithelial cell adhesion, and virulence factor secretion. Through comprehensive immunoinformatic analysis combining secondary structure prediction and molecular docking simulations, we identified and optimized a multi-epitope construct (UHFV) comprising immunodominant regions from four critical antigens: urease B (UreB, U), flagellin A (FlaA, F), adhesin A (HpaA, H), and vacuolating cytotoxin A (VacA, V). This ensemble of epitopes was subsequently displayed on a self-assembling ferritin (Fn) nanoparticle platform to generate the particulate antigen UHFV-Fn. To further enhance mucosal delivery, we engineered a mucoadhesive delivery system using biocompatible hydroxypropyltrimethyl ammonium chloride chitosan (HACC), which significantly improved antigen stability and bioavailability. The resulting UHFV-Fn@HACC vaccine formulation demonstrated robust protective effect, eliciting potent H. pylori-specific CD4⁺ T cell responses and showing remarkable prophylactic efficacy in vivo. Such a multi-component vaccine design represents a notable advancement in the development of effective H. pylori immunization strategies.