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Dendritic cells prevent rather than promote immunity conferred by a helicobacter vaccine using a mycobacterial adjuvant.

AbstractBACKGROUND & AIMS:
Immunization against the gastric bacterium Helicobacter pylori could prevent many gastric cancers and other disorders. Most vaccination protocols used in preclinical models are not suitable for humans. New adjuvants and a better understanding of the correlates and requirements for vaccine-induced protection are needed to accelerate development of vaccines for H pylori.
METHODS:
Vaccine-induced protection against H pylori infection and its local and systemic immunological correlates were assessed in animal models, using cholera toxin or CAF01 as adjuvants. The contribution of B cells, T-helper (Th)-cell subsets, and dendritic cells to H pylori-specific protection were analyzed in mice.
RESULTS:
Parenteral administration of a whole-cell sonicate, combined with the mycobacterial cell-wall-derived adjuvant CAF01, protected against infection with H pylori and required cell-mediated, but not humoral, immunity. The vaccine-induced control of H pylori was accompanied by Th1 and Th17 responses in the gastric mucosa and in the gut-draining mesenteric lymph nodes; both Th subsets were required for protective immunity against H pylori. The numbers of memory CD4+ T cells and neutrophils in gastric tissue were identified as the best correlates of protection. Systemic depletion of dendritic cells or regulatory T cells during challenge infection significantly increased protection by overriding immunological tolerance mechanisms activated by live H pylori.
CONCLUSIONS:
Parenteral immunization with a Helicobacter vaccine using a novel mycobacterial adjuvant induces protective immunity against H pylori that is mediated by Th1 and Th17 cells. Tolerance mechanisms mediated by dendritic cells and regulatory T cells impair H pylori clearance and must be overcome to improve immunity.
AuthorsIris Hitzler, Mathias Oertli, Burkhard Becher, Else Marie Agger, Anne Müller
JournalGastroenterology (Gastroenterology) Vol. 141 Issue 1 Pg. 186-96, 196.e1 (Jul 2011) ISSN: 1528-0012 [Electronic] United States
PMID21569773 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Bacterial Vaccines
  • Cancer Vaccines
  • Cholera Toxin
Topics
  • Adjuvants, Immunologic (administration & dosage, pharmacology)
  • Administration, Intranasal
  • Administration, Oral
  • Animals
  • Antibodies, Bacterial (immunology)
  • B-Lymphocytes (drug effects, immunology, microbiology)
  • Bacterial Vaccines (administration & dosage, pharmacology)
  • Cancer Vaccines (administration & dosage, pharmacology)
  • Cell Wall (immunology)
  • Chemotaxis (drug effects)
  • Cholera Toxin (immunology)
  • Dendritic Cells (drug effects, immunology, microbiology)
  • Helicobacter Infections (immunology, microbiology, prevention & control)
  • Helicobacter pylori (immunology)
  • Immune Tolerance (drug effects)
  • Immunity, Cellular (drug effects)
  • Immunity, Humoral (drug effects)
  • Injections, Intraperitoneal
  • Injections, Subcutaneous
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mycobacterium (immunology)
  • Stomach (drug effects, immunology, microbiology)
  • Stomach Neoplasms (immunology, microbiology, prevention & control)
  • T-Lymphocytes, Helper-Inducer (drug effects, immunology, microbiology)
  • T-Lymphocytes, Regulatory (drug effects, immunology, microbiology)
  • Time Factors

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