Antibodies derived from an enterotoxigenic Escherichia coli (ETEC) adhesin tip MEFA (multiepitope fusion antigen) against adherence of nine ETEC adhesins: CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, CS21 and EtpA.
Antibodies derived from an enterotoxigenic Escherichia coli (ETEC) adhesin tip MEFA (multiepitope fusion antigen) against adherence of nine ETEC adhesins: CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, CS21 and EtpA.
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源自产肠毒素大肠杆菌 (ETEC) 粘附素尖端 MEFA（多表位融合抗原）的抗体，可抵抗九种 ETEC 粘附素的粘附：CFA/I、CS1、CS2、CS3、CS4、CS5、CS6、CS21 和 EtpA。
DOI：
10.1016/j.vaccine.2016.04.003
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发表时间：
2016-06-30
期刊：
影响因子：
5.5
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Nandre RM;Ruan X;Duan Q;Sack DA;Zhang W
腹泻仍然是发展中国家5岁以下儿童死亡的主要原因。产肠毒素大肠杆菌（ETEC）是引起儿童腹泻和旅行者腹泻的主要细菌。ETEC细菌通过附着在上皮细胞的宿主受体上并在小肠中定殖而引发小肠疾病。因此，防止ETEC附着被认为是ETEC腹泻的第一道防线。然而，开发有效对抗ETEC细菌粘附的疫苗遇到了挑战，因为ETEC菌株产生超过23种免疫异质性粘附素。本研究应用MEFA（multiepitope fusion antigen）方法整合CFA/I、CS 1、CS2、CS3、CS4、CS5、CS6、CS21和EtpA粘附素的粘附素末端或粘附亚基的表位，构建粘附素末端MEFA肽。然后，我们检查了这种尖端MEFA在小鼠免疫中的免疫原性，并评估了这种尖端MEFA在ETEC疫苗开发中的潜在应用。数据显示，用这种粘附素尖端MEFA腹腔内免疫的小鼠产生了对所有9种ETEC粘附素的IgG抗体应答。ETEC和E.表达这九种粘附素的大肠杆菌细菌在与免疫小鼠的血清孵育后，表现出对Caco-2细胞的粘附显著减少。这些结果表明，这种粘附素尖端MEFA诱导的抗粘附素抗体阻断了最重要的ETEC粘附素的粘附，表明这种多价尖端MEFA可能有助于开发针对ETEC腹泻的广泛保护性抗粘附素疫苗。
Diarrhea continues to be a leading cause of death in children younger than 5 years in developing countries. Enterotoxigenic Escherichia coli (ETEC) is a leading bacterial cause of children’s diarrhea and travelers’ diarrhea. ETEC bacteria initiate diarrheal disease by attaching to host receptors at epithelial cells and colonizing in small intestine. Therefore, preventing ETEC attachment has been considered the first line of defense against ETEC diarrhea. However, developing vaccines effectively against ETEC bacterial attachment encounters challenge because ETEC strains produce over 23 immunologically heterogeneous adhesins. In this study, we applied MEFA (multiepitope fusion antigen) approach to integrate epitopes from adhesin tips or adhesive subunits of CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, CS21 and EtpA adhesins and to construct an adhesin tip MEFA peptide. We then examined immunogenicity of this tip MEFA in mouse immunization, and assessed potential application of this tip MEFA for ETEC vaccine development. Data showed that mice intraperitoneally immunized with this adhesin tip MEFA developed IgG antibody responses to all nine ETEC adhesins. Moreover, ETEC and E. coli bacteria expressing these nine adhesins, after incubation with serum of the immunized mice, exhibited significant reduction in attachment to Caco-2 cells. These results indicated that anti-adhesin antibodies induced by this adhesin tip MEFA blocked adherence of the most important ETEC adhesins, suggesting this multivalent tip MEFA may be useful for developing a broadly protective anti-adhesin vaccine against ETEC diarrhea.