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

Journal of Medical Microbiology - Tập 73 Số 1 - 2024
Thị Kim Cúc Nguyễn1, Hoang Dang Khoa2, Thi Lan Phuong Nguyen3, Thu Thuy Pham1, Bao Ngoc Mach2, Thi Chinh Nguyen1, Thi Lan Pham1, Paidamoyo M. Katsande4, Huynh A. Hong4, Huu Thai Duong3, Anh N. Phan5, Simon M. Cutting4, Minh Thiet Vu2, Văn Duy Nguyễn1,5
1Institute of Biotechnology and Environment, Nha Trang University, 2 Nguyen Dinh Chieu Street, Khanh Hoa, Vietnam
2NTT Hi-Tech Institute, Nguyen Tat Thanh University, 300A Nguyen Tat Thanh, Ho Chi Minh City, Vietnam
3Institute of Vaccines and Biological Medicals (IVAC), 9 Pasteur Street, Nha Trang, Khanh Hoa, Vietnam
4Department of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 0EX, UK
5School of Engineering, Newcastle University, Newcastle upon Tyne NE1 7RU, UK

Tóm tắt

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.

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Journal of Medical Microbiology

Tập 73 Số 1

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