A novel multi-epitope vaccine induces protective and therapeutic immunity against Helicobacter pylori

The development of an effective vaccine against Helicobacter pylori remains a major global health priority, aimed at reducing infection prevalence and preventing diseases such as chronic gastritis, peptic ulcers, and gastric cancer. Despite extensive research, no vaccine has yet demonstrated durable efficacy in clinical settings. This study describes the development of a novel multi-epitope vaccine targeting H. pylori. Sixteen B- and T-cell epitopes derived from six virulence factors were identified using bioinformatics tools and assembled into a Multi-Epitope Unit (MEU) antigen. The MEU antigen was formulated either as a flagellin-adjuvanted protein or delivered via a recombinant Modified Vaccinia virus Ankara (MVA) viral vector. Vaccine immunogenicity and efficacy were assessed in H. pylori SS1-challenged mice. Both formulations induced robust MEU-specific antibody and CD4⁺ T-cell responses, with the strongest immune responses observed following MEU-flagellin priming combined with MVA-MEU. The vaccines elicited balanced Th1/Th2 immunity and increased CD4⁺NKT-like cells frequencies. Notably, heterologous prime-boost vaccination or two doses of the MVA-MEU achieved complete bacterial clearance in both prophylactic and therapeutic models. These findings support the potential of MEU-based vaccines for preventing and treating H. pylori infection, thereby providing a strong rationale for advancement into toxicology studies clinical development.