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. Kwong; Mario Roederer; Richard T. Wyatt; Gary J. Nabel; John R. Mascola

doi:10.1126/science.1187659

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 journal › Article › peer-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 language	English (US)
Pages (from-to)	856-861
Number of pages	6
Journal	Science
Volume	329
Issue number	5993
DOIs	https://doi.org/10.1126/science.1187659
State	Published - Aug 13 2010
Externally published	Yes

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Wu, X., Yang, Z. Y., Li, Y., Hogerkorp, C. M., Schief, W. R., Seaman, M. S., Zhou, T., Schmidt, S. D., Wu, L., Xu, L., Longo, N. S., McKee, K., O'Dell, S., Louder, M. K., Wycuff, D. L., Feng, Y., Nason, M., Doria-Rose, N., Connors, M., ... Mascola, J. R. (2010). Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science, 329(5993), 856-861. https://doi.org/10.1126/science.1187659

Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. / Wu, Xueling; Yang, Zhi Yong; Li, Yuxing; Hogerkorp, Carl Magnus; Schief, William R.; Seaman, Michael S.; Zhou, Tongqing; Schmidt, Stephen D.; Wu, Lan; Xu, Ling; Longo, Nancy S.; McKee, Krisha; O'Dell, Sijy; Louder, Mark K.; Wycuff, Diane L.; Feng, Yu; Nason, Martha; Doria-Rose, Nicole; Connors, Mark; Kwong, Peter D.; Roederer, Mario; Wyatt, Richard T.; Nabel, Gary J.; Mascola, John R.

In: Science, Vol. 329, No. 5993, 13.08.2010, p. 856-861.

Research output: Contribution to journal › Article › peer-review

Wu, X, Yang, ZY, Li, Y, Hogerkorp, CM, 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 2010, 'Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1', Science, vol. 329, no. 5993, pp. 856-861. https://doi.org/10.1126/science.1187659

Wu, Xueling ; Yang, Zhi Yong ; Li, Yuxing ; Hogerkorp, Carl Magnus ; Schief, William R. ; Seaman, Michael S. ; Zhou, Tongqing ; Schmidt, Stephen D. ; Wu, Lan ; Xu, Ling ; Longo, Nancy S. ; McKee, Krisha ; O'Dell, Sijy ; Louder, Mark K. ; Wycuff, Diane L. ; Feng, Yu ; Nason, Martha ; Doria-Rose, Nicole ; Connors, Mark ; Kwong, Peter D. ; Roederer, Mario ; Wyatt, Richard T. ; Nabel, Gary J. ; Mascola, John R. / Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. In: Science. 2010 ; Vol. 329, No. 5993. pp. 856-861.

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title = "Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1",

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.",

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

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AU - Louder, Mark K.

AU - Wycuff, Diane L.

AU - Feng, Yu

AU - Nason, Martha

AU - Doria-Rose, Nicole

AU - Connors, Mark

AU - Kwong, Peter D.

AU - Roederer, Mario

AU - Wyatt, Richard T.

AU - Nabel, Gary J.

AU - Mascola, John R.

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AB - 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.

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

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