{
  "abstract": "Background. Helicobacter pylori colonises 40-45% of the global population, is a WHO Group I carcinogen, and is increasingly hard to eradicate amid rising resistance; no vaccine is licensed. CagW, a VirB6-family cagPAI component, has been advanced as a DNA-vaccine antigen that protects mice; a codon-optimised CagW-Fc mRNA in lipid nanoparticles (mRNA-LNP) is a candidate antigen design intended to engage humoral and cellular immunity. To define the infected gastric mucosal niche in which such a vaccine must operate, we mined public sequencing, single-cell and metabolomics repositories. Methods. NCBI GEO, MetaboLights and NCBI Protein were interrogated. Bulk transcriptomes of H. pylori-infected vs uninfected gastric epithelial cells (GSE295523; 24 libraries: HGC27, AGS, MKN45, GES-1) were re-analysed with a cell-line-blocked design; DEGs (BH-adjusted) were annotated via g:Profiler (GO, KEGG, Reactome) and 13 functional signatures scored. Single-cell composition was quantified from a mouse gastric scRNA-seq atlas (GSE224840; 16,434 cells) and sorted gastric CD8+ tissue-resident memory (TRM) vs splenic memory T cells (GSE216894). Targeted gastric metabolomics was re-analysed for epithelial ornithine decarboxylase (Odc) deletion (MTBLS3235) and cystathionine-gamma-lyase (Cth) deletion (MTBLS2851). CagW conservation was computed across 400 NCBI records (286 variants) with Kyte-Doolittle topology and four B cell epitope scales. Results. Infection induced 326 up- and 115 down-regulated genes (FDR < 0.05, |log2FC| > 1), dominated by TNF/NF-kappaB (KEGG hsa04668, P=5.5x10-11), integrated stress response (ATF4-CHAC1-DDIT3-TRIB3-ASNS) and Th17 chemokines (CXCL8 +3.43, CCL20 +1.32, CXCL1 +1.30, IL23A +1.02). MHC-I presentation rose (Delta-z +0.76; MHC-II unchanged); the arginine/polyamine module (SLC7A1 +1.19, ARG2 +1.33, SAT1 +1.50, ODC1 +0.58) was co-induced. scRNA-seq showed immune expansion in infected mucosa (39.8% vs 21.2% cells; OR 2.46; cell-level frequencies reported descriptively because cells are not independent; direction confirmed at sample level, n=4 vs 4), driven by plasmacytoid DCs (OR 8.9), neutrophils (OR 3.0), macrophages (OR 2.7) and cDCs (OR 2.1), with epithelial de-differentiation. Gastric CD8+ TRM cells showed a residency-effector program (Itgae +6.2, Cd69 +2.3, Gzmb +4.8, Ifng +5.3) with egress-gene loss (Sell -11.4, S1pr1 -9.7, Klf2 -5.2). Metabolomics confirmed both nodes: Odc deletion raised arginine (+3.08) and Cth deletion raised spermidine (+0.40) while lowering leukotriene B4 (-0.33). CagW was conserved across 286 variants (median 98.3% identity; 96.4% residues >=95% conserved), carried four transmembrane helices, and showed a surface-biased conserved epitope envelope at residues 505-530 and 63-79. Conclusions. Public multi-omics define an NF-kappaB/ATF4-driven, Th17-polarised, metabolically stressed niche where antigen-presenting cells expand, epithelium de-differentiates, and CD8+ TRM cells act locally. Here CagW is exceptional among cagPAI antigens: near-universal conservation plus an accessible, conserved surface. These findings provide a systems-level rationale for prioritising CagW as a conserved, epitope-accessible vaccine antigen and inform next-generation multi-antigen designs.",
  "abstract_shown": true,
  "affiliations": [
    "Ruijin Hospital, Shanghai Jiao Tong University School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Y. Zhao"
    },
    {
      "name": "H. Cheng"
    },
    {
      "name": "S. Zhou"
    },
    {
      "name": "L. He"
    },
    {
      "name": "C. Xiu"
    },
    {
      "name": "B. Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "X. Lu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b4snrkjjt0a86.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.30.763066",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763066v1.full",
  "id": "b4snrkjjt0a86",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763066v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763066v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b4snrkjjt0a86.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:20:58Z",
      "native_id": "10.64898/2026.10.30.763066",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763066v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Integrative multi-omics re-analysis of public sequencing and metabolomics repositories defines the mucosal immune and metabolic landscape of Helicobacter pylori infection and supports CagW as a rational mRNA-LNP vaccine antigen",
  "title_text": "Integrative multi-omics re-analysis of public sequencing and metabolomics repositories defines the mucosal immune and metabolic landscape of Helicobacter pylori infection and supports CagW as a rational mRNA-LNP vaccine antigen",
  "type": "preprint",
  "updated_at": "2026-11-02T00:21:21Z",
  "url": "https://research.draconitic.com/paper/b4snrkjjt0a86",
  "venue": "bioRxiv",
  "versions": []
}