Protection of mice against enterotoxigenic E. coli by immunization with a polyvalent enterotoxin comprising a combination of LTB, STa, and STb
Protection of mice against enterotoxigenic E. coli by immunization with a polyvalent enterotoxin comprising a combination of LTB, STa, and STb
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通过使用包含 LTB、STa 和 STb 组合的多价肠毒素免疫来保护小鼠免受产肠毒素大肠杆菌的侵害
DOI：
10.1007/s00253-010-2991-7
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发表时间：
2011-03-01
影响因子：
5
通讯作者：
Jin, Liji
中科院分区：
文献类型：
--
作者：
You, Jiansong;Xu, Yongping;Jin, Liji
目前可用的产肠毒素大肠杆菌 (ETEC) 疫苗基于定植因子和/或不耐热肠毒素 B 亚基 (LTB)。然而，针对热稳定性肠毒素 a (STa) 和 b (STb) 的抗毒性反应的诱导具有优点，因为这两种免疫原性较差的毒素经常与 ETEC 菌株相关。在本研究中，我们通过基因构建了一种三价肠毒素融合蛋白（STa-LTB-STb，缩写为 SLS），旨在开发一种含有这三种肠毒素的单一类毒素，用于 ETEC 疫苗接种。 STa 中一个形成二硫键的半胱氨酸的诱变导致 SLS 的 STa 毒性显着降低；然而，融合肽保留了 STb 相关的毒性。用 SLS 蛋白免疫小鼠可引发针对 LTB、STa 和 STb 的显着抗体反应。值得注意的是，小鼠抗血清能够中和 STa 和 STb 的生物活性。在评估SLS免疫保护作用的实验中，接受SLS的小鼠在腹腔内接受ETEC攻击后的死亡率显着低于对照组（P < 0.01）。这些结果表明，三价融合肠毒素 SLS 有潜力作为一种有用的毒素疫苗，通过单一免疫原对抗 ETEC 诱导的腹泻病。
Currently available enterotoxigenic Escherichia coli (ETEC) vaccines are based on colonization factors and/or the heat-labile enterotoxin B subunit (LTB). However, the induction of antitoxic responses against heat-stable enterotoxin a (STa) and b (STb) has merit as these two poorly immunogenic toxins are frequently associated with ETEC strains. In this study, we genetically constructed a trivalent enterotoxin fusion protein (STa-LTB-STb, abbreviated to SLS) in an effort to develop a single toxoid containing these three enterotoxins for vaccination against ETEC. Mutagenesis at one disulfide-bridge-forming cysteine in STa led to a dramatic reduction in the STa toxicity of SLS; however, the fusion peptide retained the STb-associated toxicity. Immunization of mice with SLS protein elicited significant antibody responses to LTB, STa, and STb. Significantly, the mice antisera were able to neutralize the biological activity of both STa and STb. In the experiment to assess the protective effect of SLS immunization, the mortality of mice receiving SLS was significantly lower than their control cohorts (P < 0.01) after intraperitoneal challenge with ETEC. These results show that the trivalent fusion enterotoxin SLS has the potential to serve as a useful toxin-based vaccine against ETEC-induced diarrheal disease via a single immunogen.