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


Hitzler, I; Oertli, M; Becher, B; Agger, E M; Müller, A (2011). Dendritic cells prevent rather than promote immunity conferred by a helicobacter vaccine using a mycobacterial adjuvant. Gastroenterology, 141(1):186-196.e1.

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.

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research

04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:06 Jun 2011 12:31
Last Modified:05 Apr 2016 14:55
Publisher:Elsevier
ISSN:0016-5085
Publisher DOI:10.1053/j.gastro.2011.04.009
PubMed ID:21569773
Permanent URL: http://doi.org/10.5167/uzh-48248

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