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

**Authors:** Hassan Moeini, Amrollah Mostafazadeh, Lars Schoenemann, Abbas Yadegar, Shaghayegh Jamshidizadeh, Kosar Nayeri, Volker Wedershoven, Florian Anderl, Christian Schulz, Bastian Popper, Peter Malfertheiner, Behnam Kalali

PMC · DOI: 10.1038/s41541-026-01409-9 · NPJ Vaccines · 2026-03-16

## TL;DR

A new multi-epitope vaccine effectively induces immunity against Helicobacter pylori in mice, offering potential for both prevention and treatment.

## Contribution

A novel multi-epitope vaccine formulation combining flagellin and MVA vector achieves complete bacterial clearance in H. pylori models.

## Key findings

- MEU-flagellin priming with MVA-MEU boost induced strongest immune responses.
- Vaccines elicited balanced Th1/Th2 immunity and increased CD4+NKT-like cells.
- Heterologous prime-boost or two MVA-MEU doses achieved complete bacterial clearance.

## Abstract

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.

## Linked entities

- **Diseases:** chronic gastritis (MONDO:0005001), gastric cancer (MONDO:0001056)
- **Species:** Helicobacter pylori (taxon 210), Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, Cd8a (CD8 subunit alpha) [NCBI Gene 12525] {aka Ly-2, Ly-35, Ly-B, Lyt-2}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, VacA [NCBI Gene 48201093], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, CagA [NCBI Gene 48200769], IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, TLR5 (toll like receptor 5) [NCBI Gene 7100] {aka MELIOS, SLE1, SLEB1, TIL3}, Tlr5 (toll-like receptor 5) [NCBI Gene 53791], NAPA (NSF attachment protein alpha) [NCBI Gene 8775] {aka SNAPA}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}
- **Diseases:** chronic gastritis (MESH:D005756), gastric adenocarcinoma (MESH:D013274), inflammatory damage (MESH:D018746), bacterial (MESH:D001424), infection (MESH:D007239), inflammatory (MESH:D007249), MEU (MESH:D015161), H. pylori Infection (MESH:D016481), peptic ulcers (MESH:D010437)
- **Chemicals:** H2SO4 (MESH:C033158), HEPES (MESH:D006531), agar (MESH:D000362), arabinose (MESH:D001089), SDS (MESH:D012967), L-Arginine (MESH:D001120), Triton X-100 (MESH:D017830), Amp (MESH:D000249), streptomycin (MESH:D013307), hydrogen (MESH:D006859), GS (-), agarose (MESH:D012685), H2O (MESH:D014867), urea (MESH:D014508), N2 (MESH:D009584), NaCl (MESH:D012965), sucrose (MESH:D013395), Tween 20 (MESH:D011136), CO2 (MESH:D002245), Brefeldin A (MESH:D020126), penicillin (MESH:D010406), PBS (MESH:D007854)
- **Species:** Salmonella (genus) [taxon 590], Ovis aries (domestic sheep, species) [taxon 9940], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Escherichia coli BL21(DE3) (strain) [taxon 469008], Helicobacter pylori (species) [taxon 210], Escherichia coli (E. coli, species) [taxon 562], Helicobacter pylori SS1 (strain) [taxon 102617], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** pEP-MVAdVI — Mus musculus (Mouse), Hybridoma (CVCL_C7KI), GS1783 — Homo sapiens (Human), Rhabdoid tumor of the kidney, Cancer cell line (CVCL_U758), /6 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_5985), MVA — Homo sapiens (Human), Cockayne syndrome type B, Finite cell line (CVCL_ZN59), pET-28b — Oryctolagus cuniculus (Rabbit), Transformed cell line (CVCL_6E94), HEK-Blue-Luci — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_5471), hTLR5 — Homo sapiens (Human), Transformed cell line (CVCL_Y396), HEK-Blue — Homo sapiens (Human), Burkitt lymphoma, Cancer cell line (CVCL_1967), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), DF-1 — Gallus gallus (Chicken), Spontaneously immortalized cell line (CVCL_XF08)

## Full text

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## Figures

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## References

2 references — full list in the complete paper: https://tomesphere.com/paper/PMC13022432/full.md

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Source: https://tomesphere.com/paper/PMC13022432