title: Designing an efficient multi-epitope oral vaccine against Helicobacter pylori using immunoinformatics and structural vaccinology approaches.
abstract: Helicobacter pylori is the cunning bacterium that can live in the stomachs of many people without any symptoms, but gradually can lead to gastric cancer. Due to various obstacles, which are related to anti-H. pylori antibiotic therapy, recently developing an anti-H. pylori vaccine has attracted more attention. In this study, different immunoinformatics and computational vaccinology approaches were employed to design an efficient multi-epitope oral vaccine against H. pylori. Our multi-epitope vaccine is composed of heat labile enterotoxin IIc B (LT-IIc) that is used as a mucosal adjuvant to enhance vaccine immunogenicity for oral immunization, cartilage oligomeric matrix protein (COMP) to increase vaccine stability in acidic pH of gut, one experimentally protective antigen, OipA, and two hypothetical protective antigens, HP0487 and HP0906, and "CTGKSC" peptide motif that target epithelial microfold cells (M cells) to enhance vaccine uptake from the gut barrier. All the aforesaid segments were joined to each other by proper linkers. The vaccine construct was modeled, validated, and refined by different programs to achieve a high-quality 3D structure. The resulting high-quality model was applied for conformational B-cell epitopes selection and docking analyses with a toll-like receptor 2 (TLR2). Moreover, molecular dynamics studies demonstrated that the protein-TLR2 docked model was stable during simulation time. We believe that our vaccine candidate can induce mucosal sIgA and IgG antibodies, and Th1/Th2/Th17-mediated protective immunity that are crucial for eradicating H. pylori infection. In sum, the computational results suggest that our newly designed vaccine could serve as a promising anti-H. pylori vaccine candidate.
authors.affiliation: Pharmaceutical Science Research Center, Shiraz University of Medical Science, Shiraz, Iran.
authors.forename: Navid
authors.initials: N
authors.lastname: Nezafat
authors.affiliation: Pharmaceutical Science Research Center, Shiraz University of Medical Science, Shiraz, Iran.
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Eslami
authors.affiliation: Pharmaceutical Science Research Center, Shiraz University of Medical Science, Shiraz, Iran and Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. ghasemiy@sums.ac.ir.
authors.forename: Manica
authors.initials: M
authors.lastname: Negahdaripour
authors.affiliation: Pharmaceutical Science Research Center, Shiraz University of Medical Science, Shiraz, Iran and Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. ghasemiy@sums.ac.ir.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Rahbar
authors.affiliation: Pharmaceutical Science Research Center, Shiraz University of Medical Science, Shiraz, Iran and Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. ghasemiy@sums.ac.ir and Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Younes
authors.identifier: http://orcid.org/0000-0001-9470-1278
authors.initials: Y
authors.lastname: Ghasemi
mesh_terms: D000284:Administration, Oral; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D016208:Databases, Factual; D018604:Epitope Mapping / Q000379:methods; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D016481:Helicobacter Infections / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D057188:Workflow
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D000939:Epitopes; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte