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

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.

Clinical testing of an inactivated influenza A/H5N1 vaccine candidate in a double-blinded, placebo-controlled, randomized trial in healthy adults in Vietnam.

We tested an inactivated egg-grown whole virus influenza A/H5N1 vaccine candidate developed by the Institute of Vaccines and Medical Biologicals (IVAC), a state-run vaccine manufacturer in Vietnam, in a Phase 1, placebo controlled, double blinded, randomized trial. The vaccine was adjuvanted with aluminum hydroxide. The trial enrolled 75 subjects who were randomized to receive two injections of one of the following: low-dose of vaccine (7.5 mcg HA), high-dose of vaccine (15 mcg HA), or placebo. The vaccine candidate was well tolerated with minimal local reactogenicity consisting of mild, short-lived injection site pain and/or tenderness. No systemic reactogenicity was observed other than transient low-grade fever in about 13% of the subjects and no unsolicited adverse events were attributable to product administration. Immune responses were assessed at baseline and after the first and second dose by hemagglutination inhibition (HAI) and microneutralization (MN) assays, with 72% of the high-dose and 68% of the low-dose vaccine recipients presenting a ⩾4-fold response in the HAI assay and 72% of the high-dose and 61% of the low-dose vaccine recipients exhibiting a ⩾4-fold response in the MN assay. These promising results support further development. ClinicalTrials.gov number NCT02171819, June 20, 2014.