Enhanced immunogenicity of a novel Stx2Am-Stx1B fusion protein in a mice model of enterohemorrhagic Escherichia coli O157:H7 infection
Enhanced immunogenicity of a novel Stx2Am-Stx1B fusion protein in a mice model of enterohemorrhagic Escherichia coli O157:H7 infection
复制标题
新型 Stx2Am-Stx1B 融合蛋白在肠出血性大肠杆菌 O157:H7 感染小鼠模型中增强免疫原性
DOI：
10.1016/j.vaccine.2010.11.035
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发表时间：
2011-01-29
期刊：
影响因子：
5.5
通讯作者：
Wang, Hui
中科院分区：
文献类型：
--
作者：
Cai, Kun;Gao, Xiang;Wang, Hui
志贺滋贺毒素（Stx）包括由EHEC O157：H7产生的Stx 1和Stx 2，其导致严重的疾病，包括人类的溶血性尿毒综合征（HUS）。本实验室前期研究制备了Stx2B-Stx1B（简称25）融合蛋白，并对大肠杆菌低致死量攻击具有免疫原性。coli0157：H7。为了提高Stx1B和Stx2A的免疫原性，我们构建了一种新的融合蛋白Stx2Am-Stx1B（简称SAmB）。融合蛋白SAmB在小鼠中引起高水平的体液IgG和IgG 1，并诱导Th2-典型的细胞因子IL-4/IL-10，但不诱导Th1-典型的细胞因子INF-γ，表明部分体液免疫应答由Th2-型细胞介导，有助于这种体液反应性。SAmB诱导的抗Stx 2中和抗体水平高于2S。对高致死量E. coli0157：H7，对纯化的Stx1和Stx2具有交叉保护作用。(C)2010爱思唯尔有限公司版权所有。
Shiga toxins (Stxs) which include Stx1 and Stx2 produced by EHEC O157:H7 are responsible for severe diseases, including hemolytic uremic syndrome (HUS) in humans. In our previous study, a fusion protein Stx2B-Stx1B (25 for short) was prepared and displayed immunogenicity against low lethal dose challenge of E. coli 0157:H7. To enhance the immunogenicity against both toxins above, we constructed a novel fusion protein carrying the stx1B subunit and enzyme-inactive Stx2A subunit, designated Stx2Am-Stx1B (SAmB for short). The fusion protein SAmB elicited high level humoral IgG and IgG1 in mice and induced Th2-typical cytokines IL-4/IL-10 but not Th1-typical cytokine INF-gamma, indicating a partial to humoral immunoresponse mediated by Th2-type cells that contributed to this humoral reactivity. Higher level neutralizing antibodies against Stx2 were elicited by SAmB than 2S. An enhanced effect of protection (93.3%) against high lethal dose challenge of lysed E. coli 0157:H7 was observed, and the SAmB also provided cross protection against purified Stx1 and Stx2. (C) 2010 Elsevier Ltd. All rights reserved.