A Novel Humanized Anti-Abrin A Chain Antibody Inhibits Abrin Toxicity In Vitro and In Vivo.

A Novel Humanized Anti-Abrin A Chain Antibody Inhibits Abrin Toxicity In Vitro and In Vivo.
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新型人源化抗相思豆蛋白 A 链抗体在体外和体内抑制相思豆蛋白毒性

DOI:
10.3389/fimmu.2022.831536
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发表时间:
2022
影响因子:
7.3
通讯作者:
Qiao C
Qiao C
中科院分区:
医学2区
文献类型:
--
作者:
Peng J;Wu J;Shi N;Xu H;Luo L;Wang J;Li X;Xiao H;Feng J;Li X;Chai L;Qiao C

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ABRIN是Abrus precatorius种子的II核糖体灭活蛋白的ABRIN,被归类为B类Biotorrorism战争剂。由于其高毒性,动物或人类的摄入将导致多器官衰竭死亡。目前,尚无有效的药物来治疗ABRIN中毒。在这项研究中,使用计算机辅助设计的一种新型抗阿布林中和抗体(S008)是人性化的,该设计具有较低的免疫原性。与母小鼠抗阿布林单克隆抗体相似,S008具有高亲和力,并且在体外和体内都表现出针对ABRIN的保护作用,并且保护了S008在ABRIN后6小时服用S008。 S008发现它没有抑制ABRIN进入细胞,这表明对毒素具有细胞内阻断能力。总之,这项工作表明S008是一种高亲和力抗阿布林抗体,具有中和抗体,并且可能是临床治疗ABRIN中毒的极好候选者。
Abrin, a type-II ribosome inactivating protein from the seed of Abrus precatorius, is classified as a Category B bioterrorism warfare agent. Due to its high toxicity, ingestion by animals or humans will lead to death from multiple organ failure. Currently, no effective agents have been reported to treat abrin poisoning. In this study, a novel anti-abrin neutralizing antibody (S008) was humanized using computer-aided design, which possessed lower immunogenicity. Similar to the parent antibody, a mouse anti-abrin monoclonal antibody, S008 possessed high affinity and showed a protective effect against abrin both in vitro and in vivo, and protected mice that S008 was administered 6 hours after abrin. S008 was found that it did not inhibit entry of abrin into cells, suggesting an intracellular blockade capacity against the toxin. In conclusion, this work demonstrates that S008 is a high affinity anti-abrin antibody with both a neutralizing and protective effect and may be an excellent candidate for clinical treatment of abrin poisoning.
DOI: 10.3791/59687
发表时间: 2019-07-01
影响因子: 1.2
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