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来自美国国立卫生研究院过敏及传染病研究所的Mark Connors及其合作实验室分离出了一种新型抗体,它与一个未报道过的抗原表位-包膜糖蛋白gp41-gp120的作用位点相结合,广谱且高效地中和HIV-1病毒。

——2014年9月3日《自然》

 

 

 

中文翻译


【题目】识别gp41-gp120接合位置的人类抗体可广谱且有效地中和HIV-1型病毒

【译文】人单克隆抗体的分离为广谱中和HIV-1病毒的特异性前提提供着重要线索(详见ref. 1)。本文中,我们发现了一种广谱且极为有效的HIV特异性单克隆抗体,命名为35O22,它与HIV-1包膜糖蛋白(Env)上一个未报道过的抗原表位相结合。35O22对181种假病毒当中的62%有中和效果,其半抑制浓度(IC50) 均<50 μg ml−1。它对病毒中和的IC50中值为0.033 μg ml−1,是目前发现的最有效的抑制剂之一。35O22并不与测试的Env单体结合,但可以结合BG505 SOSIP.664的三聚体形式。利用定点突变以及负染色电镜技术,我们发现抗体的Fab区域与三聚体结合,它识别一个跨越gp120-gp41的保守型表位。35O22的特异性结合揭示了HIV Env上一个新的靶标位点,血清分析也表明这个表位在病毒感染状态下通常会暴露出来。与此新位点的结合可能会为目前基于单克隆抗体的免疫疗法、疾病预防以及疫苗的设计提供辅助作用。

 

英文原稿


 

[Title] Broad and potent HIV-1 neutralization by a human antibody that binds the gp41–gp120 interface

[Authors] Jinghe Huang, Byong H. Kang, Marie Pancera, Jeong Hyun Lee, Tommy Tong, Yu Feng, Ivelin S. Georgiev, Gwo-Yu Chuang,Aliaksandr Druz, Nicole A. Doria-Rose, Leo Laub, Kwinten Sliepen, Marit J. van Gils, Alba Torrents de la Peña, Ronald Derking, Per-Johan Klasse, Stephen A. Migueles, Robert T. Bailer, Munir Alam, Pavel Pugach, Barton F. Haynes, Richard T. Wyatt, Rogier W. Sanders, James M. Binley, Andrew B. Ward, John R. Mascola, Peter D. Kwong & Mark Connors

[Abstract] The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) <50 μg ml−1. The median IC50 of neutralized viruses was 0.033 μg ml−1, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.

原文地址: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13601.html

 

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