Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1
Granch 添加于 2010-7-14 13:00
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作 者
Wu X, Yang Z-Y, Li Y, Hogerkorp C-M, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L, Longo NS, McKee K, O'Dell S, Louder MK, Wycuff DL, Feng Y, Nason M, Doria-Rose N, Connors M, Kwong PD, Roederer M, Wyatt RT, Nabel GJ, Mascola JR
摘 要
Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1–infected subjects, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope (Env) structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of 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 gp120, an important insight for future HIV-1 vaccine design. -
详细资料
- 文献种类:期刊
- 期刊名称: Science
- 期刊缩写: Science
- ISBN: 0036-8075
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