Inflammation, immunity, and vaccines for <i>Helicobacter pylori</i> infection

Velin, Dominique; Straubinger, Kathrin; Gerhard, Markus

doi:10.1111/hel.12336

Cited by 31 publications

(19 citation statements)

References 42 publications

(60 reference statements)

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“…We thus conclude that the HBP-mediated pathway constitutes the initial NF-kB activating event immediately after contact of T4SS-proficient H. pylori with epithelial cells. We do not rule out that other reported NF-kB activating pathways may come into play at later stages of the infection once inflammatory cytokines or remnants of bacterial degradation are released in the infected tissue (Backert et al, 2016;Velin et al, 2016).…”

Section: Discussionmentioning

confidence: 88%

ALPK1- and TIFA-Dependent Innate Immune Response Triggered by the Helicobacter pylori Type IV Secretion System

et al. 2017

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Activation of transcription factor NF-κB is a hallmark of infection with the gastric pathogen Helicobacter pylori, associated with inflammation and carcinogenesis. Genome-wide RNAi screening revealed numerous host factors involved in H. pylori-, but not IL-1β- and TNF-α-dependent NF-κB regulation. Pathway analysis including CRISPR/Cas9-knockout and recombinant protein technology, immunofluorescence microscopy, immunoblotting, mass spectrometry, and mutant H. pylori strains identified the H. pylori metabolite D-glycero-β-D-manno-heptose 1,7-bisphosphate (βHBP) as a cagPAI type IV secretion system (T4SS)-dependent effector of NF-κB activation in infected cells. Upon pathogen-host cell contact, TIFA forms large complexes (TIFAsomes) including interacting host factors, such as TRAF2. NF-κB activation, TIFA phosphorylation, and TIFAsome formation depend on a functional ALPK1 kinase, highlighting the ALPK1-TIFA axis as a core innate immune pathway. ALPK1-TIFA-mediated NF-κB activation was independent of CagA protein translocation, indicating that CagA translocation and HBP delivery to host cells are distinct features of the pathogen's T4SS.

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Section: Discussionmentioning

confidence: 88%

ALPK1- and TIFA-Dependent Innate Immune Response Triggered by the Helicobacter pylori Type IV Secretion System

et al. 2017

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“…Despite vaccine efficacy against H. pylori infection has been shown in various animal models, the precise mechanisms of bacterial clearance remain relatively poorly understood ( 29 , 30 ). A number of studies support the view that antibody production is not required to elicit immune protection, but some studies showed that humoral immune response is critical for clearing H. pylori ( 31 , 32 ).…”

Section: Discussionmentioning

confidence: 99%

Protection Against Helicobacter pylori Infection in BALB/c Mouse Model by Oral Administration of Multivalent Epitope-Based Vaccine of Cholera Toxin B Subunit-HUUC

et al. 2018

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Vaccination is an increasingly important alternative approach to control Helicobacter pylori infection, since H. pylori resistance to previously efficacious antibiotic regimens is increased, and H. pylori eradication treatment for upper gastrointestinal diseases is becoming less successful. Fortunately, an efficient oral monovalent H. pylori vaccine has been developed. However, compared with monovalent vaccines, multivalent vaccines have the potential to induce more effective and comprehensive protection against H. pylori infection. In this study, we designed and produced a multivalent epitope-based vaccine cholera toxin B subunit (CTB)-HUUC with the intramucosal adjuvant CTB and tandem copies of B-cell epitopes (HpaA132-141, UreA183-203, and UreB321-339) and T-cell epitopes (HpaA88-100, UreA27-53, UreB229-251, UreB317-329, UreB373-385, UreB438-452, UreB546-561, CagA149-164, and CagA196-217) from H. pylori adhesion A subunit (HpaA), urease A subunit (UreA), urease B subunit (UreB), and cytotoxin-associated antigen (CagA). Serum IgG, stomach, and intestine mucosal sIgA from mice after CTB-HUUC vaccination neutralized H. pylori urease activity in vitro. CTB-HUUC vaccination promoted H. pylori-specific lymphocyte responses and a mixed CD4+ T cell immune response as indicated by IFN-γ, interleukin-4, and interleukin-17 production in mice. Both oral prophylactic and therapeutic CTB-HUUC vaccinations reduced gastric urease activity and H. pylori infection and protected stomachs in mice. Taken together, CTB-HUUC is a promising potent and safe multivalent vaccine in controlling H. pylori infection in BALB/c mouse model.

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“…It is reasonable to postulate that more prolonged persistence (ie , several decades) is more likely to be associated with a higher risk of future cancer. This information cannot be underestimated, because if childhood infections prove to be a critical factor for future development of cancer several decades later, prevention through early detection and treatment of infected children with specific risk‐associated biomarkers, or even vaccination for prevention of infection are strategies that should be considered …”

Section: Discussionmentioning

confidence: 99%

Review: Prevalence and dynamics of Helicobacter pylori infection during childhood

et al. 2017

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The prevalence of H. pylori infection varied widely in the studies included here; nevertheless, model estimates by detection type were similar, suggesting that overall, one-third of children worldwide are or have been infected. The few cohort and longitudinal studies available show variability, but most studies, show infection rates over 30%. Rather surprisingly, overall infection prevalence in symptomatic children was only slightly higher, around 40%. Studies including only one positive stool sample should be interpreted with caution as spontaneous clearance can occur.

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Inflammation, immunity, and vaccines for Helicobacter pylori infection

Cited by 31 publications

References 42 publications

ALPK1- and TIFA-Dependent Innate Immune Response Triggered by the Helicobacter pylori Type IV Secretion System

ALPK1- and TIFA-Dependent Innate Immune Response Triggered by the Helicobacter pylori Type IV Secretion System

Protection Against Helicobacter pylori Infection in BALB/c Mouse Model by Oral Administration of Multivalent Epitope-Based Vaccine of Cholera Toxin B Subunit-HUUC

Review: Prevalence and dynamics of Helicobacter pylori infection during childhood

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