Immunoinformatics-Based Multi-Epitope Vaccine Targeting Helicobacter Pylori

Abstract

Background: The rising global incidence of Helicobacter pylori-related diseases, particularly gastric cancer, underscores the urgent need for effective preventive vaccines, motivating the exploration of innovative immunoinformatic strategies to address this public health challenge.

Aims: The aim of this study was to design a multi-epitope subunit vaccine for Helicobacter pylori using an immunoinformatics approach. Specifically, the objectives were to predict potential epitopes from the flagellin B and urease B proteins, integrate the cholera toxin B subunit (CTB) as a mucosal adjuvant, and perform computational validation of the vaccine construct for antigenicity, stability, and interaction with immune receptors.

Methods: This study utilized an immunoinformatics approach to design a multi-epitope subunit vaccine, involving epitope prediction from flagellin B and urease B, integration of the cholera toxin B subunit (CTB) as a mucosal adjuvant, and computational validation through tools like VaxiJen, Phyre2, MolProbity, and HDOCK for antigenicity, structure, and docking analysis.

Results: The resulting vaccine construct comprises 406 amino acids with a molecular weight of 43 424.77 Da, exhibiting a predicted antigenic score of 1.0084, non-allergenic and non-toxic properties, and a stable physiochemical profile (instability index 23.51, GRAVY -0.425). Structural analysis suggested 99.1% (525/530) of residues in favored Ramachandran regions and 100.0% in allowed regions. Molecular docking with Toll-like receptor 5 (TLR5) indicated a superior docking score of -309.05 and a confidence score of 0.9601, outperforming TLR2 (-250.74), with 10 CTL epitopes (6 from flagellin B, 4 from urease B), 6 HTL epitopes, and 2 LBL epitopes linked by AAY, GPGPG, and KK linkers, respectively.

Conclusion: This research provides a computationally optimized vaccine design that shows potential for eliciting immune responses against H. pylori. Importantly, the findings remain entirely theoretical and require rigorous experimental validation in vitro and in vivo to assess their immunological relevance, safety, and efficacy before any translational or clinical application can be considered.

Keywords: Helicobacter Pylori; gastric cancer; gene sequences; immunodominant epitopes; immunogenicity; immunoinformatics; molecular docking; vaccine.