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烷基氢过氧化物还原酶:候选幽门螺杆菌疫苗。

Alkyl hydroperoxide reductase: a candidate Helicobacter pylori vaccine.

机构信息

Department of Clinical Medicine and Institute of Molecular Medicine, Trinity College Dublin, Ireland.

出版信息

Vaccine. 2012 Jun 6;30(26):3876-84. doi: 10.1016/j.vaccine.2012.04.002. Epub 2012 Apr 15.

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.

摘要

幽门螺杆菌(H. pylori)是慢性活动性胃炎、消化性溃疡病和胃癌的最重要病因。本研究旨在评估烷基氢过氧化物还原酶(AhpC)和甘露糖化 AhpC(mAhpC)作为候选疫苗在 H. pylori 感染的 C57BL/6J 小鼠模型中的疗效。重组 AhpC 被克隆、未经修饰形式的过表达和纯化,并在毕赤酵母中表达时被设计为在 N 和 C 末端掺入甘露糖残基。在接受 H. pylori 挑战之前,小鼠通过全身和黏膜免疫 AhpC 和全身免疫 mAhpC 进行免疫。测定血清 IgG 对 AhpC 的反应,并进行定量培养以确定疫苗接种策略的疗效。AhpC/明矾和 mAhpC/明矾的全身预防性免疫分别使 55%和 77.3%的小鼠免受感染。与全身免疫相比,AhpC/霍乱毒素的黏膜免疫不能预防感染,并引起低水平的血清 IgG。这些数据支持将 AhpC 用作预防 H. pylori 感染的潜在疫苗候选物。

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