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

被引:59
作者
Zhang, MY
Shu, YU
Phogat, S
Xiao, XD
Cham, F
Bouma, P
Choudhary, A
Feng, YR
Sanz, I
Rybak, S
Broder, CC
Quinnan, GV
Evans, T
Dimitrov, DS
机构
[1] NCI, Human Immunovirol Grp, Lab Expt & Computat Biol, CCR,NIH, Frederick, MD 21702 USA
[2] SAIC Frederick Inc, BRP, NCI, Frederick, MD 21702 USA
[3] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA
[4] Univ Rochester, Dept Med, Rochester, NY 14642 USA
[5] NCI Frederick, Biol Testing Branch, NIH, Frederick, MD 21702 USA
[6] Univ Calif Davis, Davis, CA 95616 USA
关键词
HIV; antibody; phage display; gp120; inhibitors; vaccines;
D O I
10.1016/j.jim.2003.07.003
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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. Published by Elsevier B.V.
引用
收藏
页码:17 / 25
页数:9
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