Academic Journal
Engineered self-assembly of mucoadhesive Helicobacter pylori vaccines: CD4+ T cell-dependent immunity prevents bacterial colonization.
| Τίτλος: | Engineered self-assembly of mucoadhesive Helicobacter pylori vaccines: CD4+ T cell-dependent immunity prevents bacterial colonization. |
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| Συγγραφείς: | Chen X; Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China., Hao J; Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China., Li Y; Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China., Zou Y; Guangzhou RNA Immune, Ltd., Guangzhou 510555, China., Li A; Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China., Fan Y; Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China., Ma S; Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China., Hao S; Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China., Yu S; Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China., Shen D; Guangzhou RNA Immune, Ltd., Guangzhou 510555, China; Suzhou Biomedical Industry Innovation Center, China., Deng X; Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong 999077, Hong Kong, China., Hu H; Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, China; State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Sun Yat-sen University, China. Electronic address: lsshhy@mail.sysu.edu.cn. |
| Πηγή: | Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2026 Jan 10; Vol. 389, pp. 114417. Date of Electronic Publication: 2025 Nov 27. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam : Elsevier Science Publishers, 1984- |
| Ιατρικοί όροι (MeSH): | Helicobacter pylori*/immunology , Bacterial Vaccines*/administration & dosage , Bacterial Vaccines*/immunology , Bacterial Vaccines*/chemistry , Helicobacter Infections*/prevention & control , Helicobacter Infections*/immunology , CD4-Positive T-Lymphocytes*/immunology, Chitosan/chemistry ; Ferritins/chemistry ; Ferritins/administration & dosage ; Antigens, Bacterial/immunology ; Antigens, Bacterial/administration & dosage ; Nanoparticles/chemistry ; Animals ; Female ; Mice, Inbred BALB C ; Mice ; Molecular Docking Simulation ; Humans ; Mice, Inbred C57BL |
| Περίληψη: | 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. (Copyright © 2025 Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no competing interests. |
| Contributed Indexing: | Keywords: Helicobacter pylori; Immunoinformatics-driven design; Mucosal adhesion; Oral multi-epitope vaccine; Self-assembling ferritin |
| Substance Nomenclature: | 0 (Bacterial Vaccines) 9012-76-4 (Chitosan) 9007-73-2 (Ferritins) 0 (Antigens, Bacterial) |
| Entry Date(s): | Date Created: 20251129 Date Completed: 20251218 Latest Revision: 20260630 |
| Update Code: | 20260630 |
| DOI: | 10.1016/j.jconrel.2025.114417 |
| PMID: | 41317920 |
| Βάση Δεδομένων: | MEDLINE |
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