Giuseppe
Emeritus
Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1 (Science, abstract, edited)
[Source: Science, <cite cite="http://www.sciencemag.org/cgi/content/abstract/329/5993/856">Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1 -- Wu et al. 329 (5993): 856 -- Science</cite>. Abstract, edited.]
Originally published in Science Express on 8 July 2010
Science 13 August 2010: Vol. 329. no. 5993, pp. 856 - 861
DOI: 10.1126/science.1187659
Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1
Xueling Wu,1,* Zhi-Yong Yang,1,* Yuxing Li,1,* Carl-Magnus Hogerkorp,1,(#) William R. Schief,4 Michael S. Seaman,5 Tongqing Zhou,1 Stephen D. Schmidt,1 Lan Wu,1 Ling Xu,1 Nancy S. Longo,1 Krisha McKee,1 Sijy O?Dell,1 Mark K. Louder,1 Diane L. Wycuff,1 Yu Feng,1,(??) Martha Nason,2 Nicole Doria-Rose,3 Mark Connors,3 Peter D. Kwong,1 Mario Roederer,1 Richard T. Wyatt,1,(??) Gary J. Nabel,1,? John R. Mascola1,?
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.
1 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
2 Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
3 Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
4 Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
5 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
* These authors contributed equally to this work.
(#) Present address: Department of Molecular Genetics, Novo Nordisk A/S, Novo Nordisk Park, 2760 M?l?v, Denmark.
(??) Present address: Department of Immunology and Microbial Science, and IAVI Center for Neutralizing Antibody at TSRI, Scripps Research Institute, La Jolla, CA 92037, USA.
? To whom correspondence should be addressed. E-mail: gnabel@nih.gov (G.J.N.); jmascola@nih.gov (J.R.M.)
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------<cite cite="http://www.sciencemag.org/cgi/content/abstract/329/5993/856"></cite>
[Source: Science, <cite cite="http://www.sciencemag.org/cgi/content/abstract/329/5993/856">Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1 -- Wu et al. 329 (5993): 856 -- Science</cite>. Abstract, edited.]
Originally published in Science Express on 8 July 2010
Science 13 August 2010: Vol. 329. no. 5993, pp. 856 - 861
DOI: 10.1126/science.1187659
Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1
Xueling Wu,1,* Zhi-Yong Yang,1,* Yuxing Li,1,* Carl-Magnus Hogerkorp,1,(#) William R. Schief,4 Michael S. Seaman,5 Tongqing Zhou,1 Stephen D. Schmidt,1 Lan Wu,1 Ling Xu,1 Nancy S. Longo,1 Krisha McKee,1 Sijy O?Dell,1 Mark K. Louder,1 Diane L. Wycuff,1 Yu Feng,1,(??) Martha Nason,2 Nicole Doria-Rose,3 Mark Connors,3 Peter D. Kwong,1 Mario Roederer,1 Richard T. Wyatt,1,(??) Gary J. Nabel,1,? John R. Mascola1,?
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.
1 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
2 Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
3 Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
4 Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
5 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
* These authors contributed equally to this work.
(#) Present address: Department of Molecular Genetics, Novo Nordisk A/S, Novo Nordisk Park, 2760 M?l?v, Denmark.
(??) Present address: Department of Immunology and Microbial Science, and IAVI Center for Neutralizing Antibody at TSRI, Scripps Research Institute, La Jolla, CA 92037, USA.
? To whom correspondence should be addressed. E-mail: gnabel@nih.gov (G.J.N.); jmascola@nih.gov (J.R.M.)
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------<cite cite="http://www.sciencemag.org/cgi/content/abstract/329/5993/856"></cite>