Abstract | BACKGROUND & 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.
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Authors | Iris Hitzler, Mathias Oertli, Burkhard Becher, Else Marie Agger, Anne Müller |
Journal | Gastroenterology
(Gastroenterology)
Vol. 141
Issue 1
Pg. 186-96, 196.e1
(Jul 2011)
ISSN: 1528-0012 [Electronic] United States |
PMID | 21569773
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Adjuvants, Immunologic
- Antibodies, Bacterial
- Bacterial Vaccines
- Cancer Vaccines
- Cholera Toxin
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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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