Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1

被引：1419

作者：

Wu, Xueling ^{[1
]}

Yang, Zhi-Yong ^{[1
]}

Li, Yuxing ^{[1
]}

Hogerkorp, Carl-Magnus ^{[1
]}

Schief, William R. ^{[4
]}

Seaman, Michael S. ^{[5
]}

Zhou, Tongqing ^{[1
]}

Schmidt, Stephen D. ^{[1
]}

Wu, Lan ^{[1
]}

Xu, Ling ^{[1
]}

Longo, Nancy S. ^{[1
]}

McKee, Krisha ^{[1
]}

O'Dell, Sijy ^{[1
]}

Louder, Mark K. ^{[1
]}

Wycuff, Diane L. ^{[1
]}

Feng, Yu ^{[1
]}

Nason, Martha ^{[2
]}

Doria-Rose, Nicole ^{[3
]}

Connors, Mark ^{[3
]}

Kwong, Peter D. ^{[1
]}

Roederer, Mario ^{[1
]}

Wyatt, Richard T. ^{[1
]}

Nabel, Gary J. ^{[1
]}

Mascola, John R. ^{[1
]}

机构：

[1] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[2] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA

[3] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA

[4] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[5] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

来源：

SCIENCE | 2010年 / 329卷 / 5993期

关键词：

TYPE-1; INFECTION; HIGH-AFFINITY; VIRUS; GP120; BREADTH; GLYCOPROTEIN; INDIVIDUALS; PANEL; IMMUNOGENICITY; SPECIFICITIES;

D O I：

10.1126/science.1187659

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1-infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1-infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design.

引用

页码：856 / 861

页数：6

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