Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1

Xueling Wu, Zhi Yong Yang, Yuxing Li, Carl Magnus Hogerkorp, William R. Schief, Michael S. Seaman, Tongqing Zhou, Stephen D. Schmidt, Lan Wu, Ling Xu, Nancy S. Longo, Krisha McKee, Sijy O'Dell, Mark K. Louder, Diane L. Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D. KwongMario Roederer, Richard T. Wyatt, Gary J. Nabel, John R. Mascola

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)856-861
Number of pages6
JournalScience
Volume329
Issue number5993
DOIs
StatePublished - Aug 13 2010
Externally publishedYes

ASJC Scopus subject areas

  • General

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