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Genomic and vaccine preclinical studies reveal a novel mouse-adapted Helicobacter pylori model for the hpEastAsia genotype in Southeast Asia

Lookup NU author(s): Professor Anh Phan, Dr Duy NguyenORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2024 Crown Copyright.Introduction. Helicobacter pylori infection is a major global health concern, linked to the development of various gastrointestinal diseases, including gastric cancer. To study the pathogenesis of H. pylori and develop effective intervention strategies, appropriate animal pathogen models that closely mimic human infection are essential. Gap statement. This study focuses on the understudied hpEastAsia genotype in Southeast Asia, a region marked by a high H. pylori infection rate. No mouse-adapted model strains has been reported previously. Moreover, it recognizes the urgent requirement for vaccines in developing countries, where overuse of antimicrobials is fuelling the emergence of resistance. Aim. This study aims to establish a novel mouse-adapted H. pylori model specific to the hpEastAsia genotype prevalent in Southeast Asia, focusing on comparative genomic and histopathological analysis of pathogens coupled with vaccine preclinical studies. Methodology. We collected and sequenced the whole genome of clinical strains of H. pylori from infected patients in Vietnam and performed comparative genomic analyses of H. pylori strains in Southeast Asia. In parallel, we conducted preclinical studies to assess the pathogenicity of the mouse-adapted H. pylori strain and the protective effect of a new spore-vectored vaccine candidate on male Mlac:ICR mice and the host immune response in a female C57BL/6 mouse model. Results. Genome sequencing and comparison revealed unique and common genetic signatures, antimicrobial resistance genes and virulence factors in strains HP22 and HP34; and supported clarithromycin-resistant HP34 as a representation of the hpEastAsia genotype in Vietnam and Southeast Asia. HP34-infected mice exhibited gastric inflammation, epithelial erosion and dysplastic changes that closely resembled the pathology observed in human H. pylori infection. Furthermore, comprehensive immunological characterization demonstrated a robust host immune response, including both mucosal and systemic immune responses. Oral vaccination with candidate vaccine formulations elicited a significant reduction in bacterial colonization in the model. Conclusion. Our findings demonstrate the successful development of a novel mouse-adapted H. pylori model for the hpEastAsia genotype in Vietnam and Southeast Asia. Our research highlights the distinctive genotype and pathogenicity of clinical H. pylori strains in the region, laying the foundation for targeted interventions to address this global health burden.


Publication metadata

Author(s): Nguyen TKC, Do HDK, Nguyen TLP, Pham TT, Mach BN, Nguyen TC, Pham TL, Katsande PM, Hong HA, Duong HT, Phan AN, Cutting SM, Vu MT, Nguyen VD

Publication type: Article

Publication status: Published

Journal: Journal of Medical Microbiology

Year: 2024

Volume: 73

Issue: 1

Online publication date: 18/01/2024

Acceptance date: 07/12/2023

Date deposited: 06/02/2024

ISSN (print): 0022-2615

ISSN (electronic): 1473-5644

Publisher: Microbiology Society

URL: https://doi.org/10.1099/jmm.0.001786

DOI: 10.1099/jmm.0.001786

Data Access Statement: he datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession numbers can be found in the article/Supplementary Material.

PubMed id: 38235783


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Funding

Funder referenceFunder name
MR/R026262/1
Vietnam Ministry of Science and Technology (MOST) under grant number NDT.79.GB/20

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