Journal
GASTROENTEROLOGY
Volume 141, Issue 1, Pages 186-U269Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2011.04.009
Keywords
Gastric Cancer; Bacteria; Ulcer; Gastric Adenocarcinoma
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Funding
- Cancer League of the Canton of Zurich
- Swiss National Science Foundation
- University Research Priority Program in Systems Biology
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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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