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通过噬菌体展示文库的连续抗原淘选筛选出的具有广泛交叉反应性的HIV中和人单克隆抗体Fab

Broadly cross-reactive HIV neutralizing human monoclonal antibody Fab selected by sequential antigen panning of a phage display library.

作者信息

Zhang Mei-Yun, Shu Yuuei, Phogat Sanjay, Xiao Xiaodong, Cham Fatim, Bouma Peter, Choudhary Anil, Feng Yan-Ru, Sanz Inaki, Rybak Susanna, Broder Christopher C, Quinnan Gerald V, Evans Thomas, Dimitrov Dimiter S

机构信息

Laboratory of Experimental and Computational Biology, CCR, NCI-Frederick, NIH, Bldg 469, Rm 246, P.O. Box B, Miller Drive, Frederick, MD 21702-1201, USA.

出版信息

J Immunol Methods. 2003 Dec;283(1-2):17-25. doi: 10.1016/j.jim.2003.07.003.

Abstract

Identification of broadly cross-reactive human monoclonal antibodies (mAbs) has major implications for development of vaccines, inhibitors and research tools. Here we describe a sequential antigen panning (SAP) methodology that may facilitate the selection of such antibodies. An HIV-specific antibody Fab (m18) was selected from a human Fab phage-display library by SAP against several recombinant soluble HIV envelope glycoproteins (Envs) and Env-sCD4 complexes. This Fab bound to a variety of recombinant soluble Envs (gp140s) from primary HIV isolates representing different clades, and inhibited cell fusion and virus entry mediated by Envs of primary HIV isolates. The methodology and the results may have implications for development of HIV vaccines and inhibitors, as well as for identification of antibodies to conserved epitopes on rapidly mutating viruses and cells.

摘要

鉴定具有广泛交叉反应性的人源单克隆抗体(mAb)对疫苗、抑制剂和研究工具的开发具有重要意义。在此,我们描述了一种顺序抗原淘选(SAP)方法,该方法可能有助于此类抗体的筛选。通过针对几种重组可溶性HIV包膜糖蛋白(Env)和Env-sCD4复合物进行SAP,从人源Fab噬菌体展示文库中筛选出一种HIV特异性抗体Fab(m18)。该Fab与来自代表不同分支的原发性HIV分离株的多种重组可溶性Env(gp140)结合,并抑制原发性HIV分离株Env介导的细胞融合和病毒进入。该方法和结果可能对HIV疫苗和抑制剂的开发以及对快速突变病毒和细胞上保守表位的抗体鉴定具有重要意义。

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