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Alkyl hydroperoxide reductase: a candidate Helicobacter pylori vaccine
Authors:O'Riordan Avril A  Morales Veronica Athie  Mulligan Linda  Faheem Nazia  Windle Henry J  Kelleher Dermot P
Affiliation:Department of Clinical Medicine and Institute of Molecular Medicine, Trinity College Dublin, Ireland.
Abstract:Helicobacter pylori (H. pylori) is the most important etiological agent of chronic active gastritis, peptic ulcer disease and gastric cancer. The aim of this study was to evaluate the efficacy of alkyl hydroperoxide reductase (AhpC) and mannosylated AhpC (mAhpC) as candidate vaccines in the C57BL/6J mouse model of H. pylori infection. Recombinant AhpC was cloned, over-expressed and purified in an unmodified form and was also engineered to incorporate N and C-terminal mannose residues when expressed in the yeast Pichia pastoris. Mice were immunized systemically and mucosally with AhpC and systemically with mAhpC prior to challenge with H. pylori. Serum IgG responses to AhpC were determined and quantitative culture was used to determine the efficacy of vaccination strategies. Systemic prophylactic immunization with AhpC/alum and mAhpC/alum conferred protection against infection in 55% and 77.3% of mice, respectively. Mucosal immunization with AhpC/cholera toxin did not protect against infection and elicited low levels of serum IgG in comparison with systemic immunization. These data support the use of AhpC as a potential vaccine candidate against H. pylori infection.
Keywords:CT, cholera toxin   H&  E, haematoxylin and eosin   PBS, phosphate buffered saline   OD, optical density   SPF, specific pathogen free   ELISA, enzyme linked immunosorbant assay   AhpC, alkyl hydroperoxide reductase   mAhpC, mannosylated AhpC   LB, Luria Bertani   NapA, neutrophil activating protein   Trx, thioredoxin   sc, subcutaneous   IVC, individually vented cages   IPTG, isopropyl-β-d-thiogalactopyranoside   APC, antigen presenting cell   NGS, asparagine–glycine–serine
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