Introduction

Helicobacter pylori infection affects approximately half of the global population and may lead to sever complications, including gastric cancer. Current antibiotic-based therapies face the challenge of rising resistance rates. Therefore, there is urgent medical need for an effective vaccine. Despite extensive research efforts, no H. pylori vaccine has yet made it to clinical application. Aim of our study is the development of a novel multi-epitope-based H. pylori vaccine

Aims & Methods

Sixteen selected B- and T-cell epitopes from six key virulence factors were fused to create the Multi-Epitope-Unit (MEU) antigen. Two vaccine formulations were evaluated: MEU combined with flagellin as adjuvant, and MEU incorporated into the Modified Vaccinia virus Ankara (MVA) genome for enhanced antigen delivery. The efficacy was assessed in murine models using H. pylori SS1 infection, with evaluation in both prophylactic and therapeutic settings. To explore the possible clinical relevance, crude antigens from 48 human clinical isolates of H. pylori obtained from international healthcare centers were tested for binding capacity with anti-MEU antibodies generated from immunized mice.

Results

Both vaccine formulations elicited robust MEU-specific antibody and CD4+ T-cell responses. The vaccines generated a balanced Th1/Th2 immune response profile and significantly elevated CD4+NKT-like cell levels. Complete bacterial clearance was achieved with protein-based vaccination followed by MVA boost or two doses of MVA vaccine in both prevention and treatment models. Binding assays revealed that anti-MEU antibodies demonstrated positive binding capacity to crude antigens from all 48 tested human clinical isolates (100% reactivity), confirming broad-spectrum recognition across diverse H. pylori strains from different geographical origins.

Conclusion

This study represents groundbreaking research, presenting a novel promising H. pylori vaccine candidate. The comprehensive testing against 48 human clinical isolates from international healthcare units provides unprecedented evidence of functional immune responses. Our data demonstrate 100% binding reactivity of anti-MEU antibodies to crude antigens from ALL tested clinical isolates, representing diverse geographical origins and strain variations. This finding demonstrates for the first time that a H. pylori vaccine can generate immune responses effective against a vast spectrum of human pathogenic strains, which has eluded all previous vaccine approach failures and poses high expectation for a successful clinical application. Our multi-epitope vaccine represents a novel H. pylori vaccine development, being the first to demonstrate both complete bacterial clearance in preclinical models as well as a broad-spectrum reactivity against human clinical isolates. These results provide strong scientific rationale for advancing to toxicology studies and clinical evaluation, offering the first genuine hope for both prevention and treatment of H. pylori infections in human populations worldwide.

Disclosure

BK, HM and VW are employed by Iguana Biotechnology. The remaining authors declare no conflicts of interest.