Neutralizing Monoclonal Antibody, mAb 10D8, Is an Effective Detoxicant against Abrin-a Both In Vitro and In Vivo.
Neutralizing Monoclonal Antibody, mAb 10D8, Is an Effective Detoxicant against Abrin-a Both In Vitro and In Vivo.
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中和单克隆抗体 mAb 10D8 是一种有效的体外和体内抗相思豆蛋白 (Abrin-a) 解毒剂
DOI：
10.3390/toxins14030164
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发表时间：
2022-02-23
期刊：
影响因子：
4.2
通讯作者：
Xie J
中科院分区：
文献类型：
--
作者：
Li Z;Xu H;Ma B;Luo L;Guo L;Zhang P;Zhao Y;Wang L;Xie J
相思豆蛋白 (Abrin) 是一种从相思子种子中分离出来的 II 型核糖体失活蛋白 (RIP)，其包含具有催化活性的 A 链和通过二硫键连接的凝集素样 B 链。已报道的四种相思豆同毒素具有相似的氨基酸组成，但细胞毒性不同，其中相思豆素-a是最有效的毒素。高杀伤力和容易获得使相思豆素成为潜在的生物恐怖主义制剂。然而，没有可用于治疗相思豆中毒的解毒剂，治疗仅是对症治疗。目前，中和抗体仍然是对抗生物毒素中毒最有效的疗法。在这项研究中，我们制备、鉴定并获得了一种高亲和力中和单克隆抗体 (mAb) 10D8，该抗体对相思豆素 a 或相思豆素粗提物诱导的细胞毒性和动物毒性具有有效的暴露前和暴露后保护作用。 mAb 10D8 可以挽救腹腔注射 25 × LD50 剂量 abrin-a 的小鼠免于致死并防止组织损伤。结果表明，10D8并不阻止相思豆素a与细胞的结合和内化，而是抑制相思豆素a的酶活性，减少对细胞蛋白质合成的抑制。 10D8 的高亲和力、良好的特异性和有效的抗毒效率使其成为抗相思豆蛋白治疗性抗体的有前途的候选者。
Abrin is a types II ribosome-inactivating protein (RIP) isolated from Abrus precatorious seeds, which comprises a catalytically active A chain and a lectin-like B chain linked by a disulfide bond. Four isotoxins of abrin have been reported with similar amino-acid composition but different cytotoxicity, of which abrin-a is the most potent toxin. High lethality and easy availability make abrin a potential bioterrorism agent. However, there are no antidotes available for managing abrin poisoning, and treatment is only symptomatic. Currently, neutralizing antibodies remain the most effective therapy against biotoxin poisoning. In this study, we prepared, identified, and acquired a high-affinity neutralizing monoclonal antibody (mAb) 10D8 with a potent pre- and post-exposure protective effect against cytotoxicity and animal toxicity induced by abrin-a or abrin crude extract. The mAb 10D8 could rescue the mouse injected intraperitoneally with a 25 × LD50 dose of abrin-a from lethality and prevent tissue damages. Results indicated that 10D8 does not prevent the binding and internalization of abrin-a to cells but inhibits the enzymatic activity of abrin-a and reduces protein synthesis inhibition of cells. The high affinity, good specificity, and potent antitoxic efficiency of 10D8 make it a promising candidate for therapeutic antibodies against abrin.
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影响因子：
4.1
作者：
Ninan, Elizabeth C.;James, Emmanuel
通讯作者：
James, Emmanuel
影响因子：
--
作者：
Saxena, Nandita;Bhutia, Yangchen Doma;Kaul, Ramesh Kumar
通讯作者：
Kaul, Ramesh Kumar
影响因子：
4.2
作者：
He X;Patfield S;Cheng LW;Stanker LH;Rasooly R;McKeon TA;Zhang Y;Brandon DL
通讯作者：
Brandon DL
影响因子：
9.4
作者：
Che, XY;Qiu, LW;Yuen, KY
通讯作者：
Yuen, KY
DOI：
10.2165/00139709-200322030-00002
发表时间：
2003-01-01
期刊：
Toxicological Reviews
影响因子：
--
作者：
Dickers, Kirsten J.;Bradberry, Sally M.;Vale, J. Allister
通讯作者：
Vale, J. Allister