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一种相思子毒素与相思豆凝集素的嵌合蛋白,可中和相思子毒素介导的小鼠致死性。

A chimeric protein of abrin and Abrus precatorius agglutinin that neutralizes abrin mediated lethality in mice.

作者信息

Tiwari Vinita, Bagaria Shradha, Karande Anjali A

机构信息

Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, 560012, India.

Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, 560012, India.

出版信息

Toxicon. 2017 Mar 1;127:122-129. doi: 10.1016/j.toxicon.2017.01.008. Epub 2017 Jan 11.

DOI:10.1016/j.toxicon.2017.01.008
PMID:28088476
Abstract

Abrin, a type II ribosome inactivating protein from the Abrus precatorius plant, is extremely toxic. It has been shown to be 75 times more potent than its infamous sister toxin, ricin and their potential use in bio-warfare is a cause of major concern. Although several vaccine candidates are under clinical trials for ricin, none are available against abrin. The present study proposes a chimeric protein, comprising of 1-123 amino acids taken from the A chain of abrin and 124-175 amino acids from Abrus precatorius agglutinin A chain, as a vaccine candidate against abrin intoxication. The design was based on the inclusion of the immunogenic region of the full length protein and the minimal essential folding domains required for inducing neutralizing antibody response. The chimera also contains the epitope for the only two neutralizing antibodies; D6F10 and A7C4, reported against abrin till now. Active immunization with the chimera protected all the mice challenged with 45 X LD of abrin. Also, passive transfer of antibodies raised against the chimera rescued all mice challenged with 50 X LD of toxin. Hence the chimeric protein appears to be a promising vaccine candidate against abrin induced lethality.

摘要

相思子毒素是一种来自相思子植物的II型核糖体失活蛋白,毒性极强。研究表明,其毒性比臭名昭著的姐妹毒素蓖麻毒素强75倍,它们在生物战中的潜在用途令人深感担忧。尽管目前有几种针对蓖麻毒素的候选疫苗正在进行临床试验,但尚无针对相思子毒素的疫苗。本研究提出了一种嵌合蛋白,它由相思子毒素A链的1 - 123个氨基酸和相思子凝集素A链的124 - 175个氨基酸组成,作为一种针对相思子毒素中毒的候选疫苗。该设计基于全长蛋白免疫原性区域的包含以及诱导中和抗体反应所需的最小必需折叠结构域。该嵌合体还包含迄今为止报道的仅有的两种针对相思子毒素的中和抗体D6F10和A7C4的表位。用该嵌合蛋白进行主动免疫可保护所有受到45倍致死剂量相思子毒素攻击的小鼠。此外,将针对该嵌合蛋白产生的抗体进行被动转移可挽救所有受到50倍致死剂量毒素攻击的小鼠。因此,该嵌合蛋白似乎是一种有前景的针对相思子毒素致死性的候选疫苗。

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