A Polyvalent Adhesin-Toxoid Multiepitope-Fusion-Antigen-Induced Functional Antibodies against Five Enterotoxigenic Escherichia coli Adhesins (CS7, CS12, CS14, CS17, and CS21) but Not Enterotoxins (LT and STa).
A Polyvalent Adhesin-Toxoid Multiepitope-Fusion-Antigen-Induced Functional Antibodies against Five Enterotoxigenic Escherichia coli Adhesins (CS7, CS12, CS14, CS17, and CS21) but Not Enterotoxins (LT and STa).
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DOI：
10.3390/microorganisms11102473
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发表时间：
2023-10-01
期刊：
影响因子：
4.5
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Li S;Seo H;Upadhyay I;Zhang W
肠道产毒素大肠杆菌（ETEC）黏附素CS7、CS12、CS14、CS17和CS21的流行及其与中重度腹泻的相关性使其成为ETEC疫苗的潜在靶点。目前，还没有获得许可的疫苗来预防ETEC，这是儿童腹泻和旅行者腹泻的主要原因。最近，一种多价粘附蛋白（粘附蛋白MEFA-II）被证明可以诱导抗体抑制这五种ETEC粘附素的粘附，并降低ETEC热稳定毒素（STa）的肠毒性，而STa在引起ETEC相关性腹泻中起关键作用。为了提高粘附素MEFA-II的抗STa毒素和其他ETEC毒素热不稳定毒素（LT）的功能抗体，我们通过添加另一个STa类毒素和LT表位对粘附素MEFA-II进行了修饰；我们检测了新抗原的免疫原性（对五种粘附素和两种毒素），更重要的是抗体对ETEC粘附和STa和LT肠毒性的功能。数据显示，用新抗原（粘附素MEFA-IIb）肌内免疫的小鼠对靶向粘附素（CS7、CS12、CS14、CS17和CS21）和毒素（STa和LT）产生了强大的IgG应答。小鼠抗体抑制表达这五种粘附素的ETEC菌株的粘附，但不能中和STa或LT的肠毒性。在进一步的研究中，粘附素MEFA-IIb肌内免疫家兔产生了强大的抗原特异性抗体；当用表达CS21粘附素（JF2101、CS21和STa）的ETEC分离物攻毒时，免疫后的家兔肠道内ETEC细菌的定植显著减少。这些数据表明粘附素MEFA-IIb具有广泛的免疫原性，并诱导针对靶向ETEC粘附素而不是毒素的功能抗体。
The increasing prevalence and association with moderate-to-severe diarrhea make enterotoxigenic Escherichia coli (ETEC) adhesins CS7, CS12, CS14, CS17, and CS21 potential targets of ETEC vaccines. Currently, there are no vaccines licensed to protect against ETEC, a top cause of children’s diarrhea and travelers’ diarrhea. Recently, a polyvalent adhesin protein (adhesin MEFA-II) was demonstrated to induce antibodies that inhibited adherence from these five ETEC adhesins and reduced the enterotoxicity of ETEC heat-stable toxin (STa), which plays a key role in causing ETEC-associated diarrhea. To improve adhesin MEFA-II for functional antibodies against STa toxin and the other ETEC toxin, heat-labile toxin (LT), we modified adhesin MEFA-II by adding another STa toxoid and an LT epitope; we examined the new antigen immunogenicity (to five adhesins and two toxins) and more importantly antibody functions against ETEC adherence and STa and LT enterotoxicity. Data show that mice intramuscularly immunized with the new antigen (adhesin MEFA-IIb) developed robust IgG responses to the targeted adhesins (CS7, CS12, CS14, CS17, and CS21) and toxins (STa and LT). Mouse antibodies inhibited the adherence of ETEC strains expressing any of these five adhesins but failed to neutralize STa or LT enterotoxicity. In further studies, rabbits intramuscularly immunized with adhesin MEFA-IIb developed robust antigen-specific antibodies; when challenged with an ETEC isolate expressing CS21 adhesin (JF2101, CS21, and STa), the immunized rabbits showed a significant reduction in intestinal colonization by ETEC bacteria. These data indicate that adhesin MEFA-IIb is broadly immunogenic and induces functional antibodies against the targeted ETEC adhesins but not the toxins.
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DOI：
10.1007/978-1-0716-1900-1_10
发表时间：
2022
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Duan, Qiangde;Huang, Jiachen;Zhang, Weiping
通讯作者：
Zhang, Weiping
影响因子：
168.9
作者：
Kotloff, Karen L.;Nataro, James P.;Levine, Myron M.
通讯作者：
Levine, Myron M.
影响因子：
15.9
作者：
Gaastra, W;Svennerholm, AM
通讯作者：
Svennerholm, AM
影响因子：
3.7
作者：
Zhang C;Knudsen DE;Liu M;Robertson DC;Zhang W;STa Toxoid Vaccine Consortium Group
通讯作者：
STa Toxoid Vaccine Consortium Group