A Tripartite Fusion, FaeG-FedF-LT192A2:B, of Enterotoxigenic Escherichia coli (ETEC) Elicits Antibodies That Neutralize Cholera Toxin, Inhibit Adherence of K88 (F4) and F18 Fimbriae, and Protect Pigs against K88ac/Heat-Labile Toxin Infection
A Tripartite Fusion, FaeG-FedF-LT192A2:B, of Enterotoxigenic Escherichia coli (ETEC) Elicits Antibodies That Neutralize Cholera Toxin, Inhibit Adherence of K88 (F4) and F18 Fimbriae, and Protect Pigs against K88ac/Heat-Labile Toxin Infection
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DOI：
10.1128/cvi.05120-11
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发表时间：
2011-10-01
影响因子：
--
通讯作者：
Zhang, Weiping
中科院分区：
文献类型：
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作者：
Ruan, Xiaosai;Liu, Mei;Zhang, Weiping
表达K88（F4）或F18菌毛和热不稳定（LT）和/或热稳定（ST）毒素的肠致病性大肠杆菌（ETEC）菌株是仔猪腹泻的主要原因。诱导抗粘附素（抗K88和抗F18）和抗毒素（抗LT和抗ST）免疫的有效疫苗可为仔猪提供广泛的ETEC保护。在这项研究中，我们将编码来自K88 ac主要亚基FaeG、F18次要亚基FedF和LT类毒素（LT 192）A2和B亚基的肽的核苷酸进行基因融合，形成三重粘附素-粘附素-类毒素融合体（FaeG-FedF-LT（192）A2：B）。将该融合物用于小鼠和猪中的免疫以评估抗粘附素和抗毒素抗体的诱导。此外，在无菌仔猪攻毒模型中评价了引发的抗粘附素和抗毒素抗体对猪ETEC菌株的保护作用。数据显示该FaeG-FedF-LT（192）A2：B融合物在免疫的小鼠和猪中引发抗K88、抗F18和抗LT抗体。此外，抗猪抗体引起中和霍乱毒素和抑制粘附对K88和F18菌毛。此外，免疫仔猪在用ETEC菌株30302（K88 ac/LT/STb）攻毒时受到保护，未发生临床疾病。相比之下，所有对照未接种仔猪在用相同ETEC菌株攻毒后均发生重度腹泻和脱水。该研究清楚地表明，该FaeG-FedF-LT（192）A2：B融合抗原引发中和LT毒素并抑制K88和F18菌毛E.大肠杆菌菌株，该融合蛋白可作为抗猪ETEC腹泻疫苗的抗原。此外，本研究中使用的粘附素-类毒素融合方法可能为开发针对人类ETEC腹泻的有效疫苗提供重要信息。
Enterotoxigenic Escherichia coli (ETEC) strains expressing K88 (F4) or F18 fimbriae and heat-labile (LT) and/or heat-stable (ST) toxins are the major cause of diarrhea in young pigs. Effective vaccines inducing antiadhesin (anti-K88 and anti-F18) and antitoxin (anti-LT and anti-ST) immunity would provide broad protection to young pigs against ETEC. In this study, we genetically fused nucleotides coding for peptides from K88ac major subunit FaeG, F18 minor subunit FedF, and LT toxoid (LT192) A2 and B subunits for a tripartite adhesin-adhesin-toxoid fusion (FaeG-FedF-LT(192)A2:B). This fusion was used for immunizations in mice and pigs to assess the induction of antiadhesin and antitoxin antibodies. In addition, protection by the elicited antiadhesin and antitoxin antibodies against a porcine ETEC strain was evaluated in a gnotobiotic piglet challenge model. The data showed that this FaeG-FedF-LT(192)A2: B fusion elicited anti-K88, anti-F18, and anti-LT antibodies in immunized mice and pigs. In addition, the anti-porcine antibodies elicited neutralized cholera toxin and inhibited adherence against both K88 and F18 fimbriae. Moreover, immunized piglets were protected when challenged with ETEC strain 30302 (K88ac/LT/STb) and did not develop clinical disease. In contrast, all control nonvaccinated piglets developed severe diarrhea and dehydration after being challenged with the same ETEC strain. This study clearly demonstrated that this FaeG-FedF-LT(192)A2: B fusion antigen elicited antibodies that neutralized LT toxin and inhibited the adherence of K88 and F18 fimbrial E. coli strains and that this fusion could serve as an antigen for vaccines against porcine ETEC diarrhea. In addition, the adhesin-toxoid fusion approach used in this study may provide important information for developing effective vaccines against human ETEC diarrhea.