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

Academic Article
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Overview

authors

  • Wu, X.
  • Yang, Z. Y.
  • Li, Yuxing
  • Hogerkorp, C. M.
  • Schief, William
  • Seaman, M. S.
  • Zhou, T. Q.
  • Schmidt, S. D.
  • Wu, L.
  • Xu, L.
  • Longo, N. S.
  • McKee, K.
  • O'Dell, S.
  • Louder, M. K.
  • Wycuff, D. L.
  • Feng, Yangbo
  • Nason, M.
  • Doria-Rose, N.
  • Connors, M.
  • Kwong, P. D.
  • Roederer, M.
  • Wyatt, Richard
  • Nabel, G. J.
  • Mascola, J. R.

publication date

  • August 2010

journal

  • Science  Journal

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.

subject areas

  • AIDS Vaccines
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibody Specificity
  • Antigens, CD4
  • B-Lymphocytes
  • Binding Sites, Antibody
  • Cross Reactions
  • Drug Design
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes
  • Genes, Immunoglobulin Heavy Chain
  • Genes, Immunoglobulin Light Chain
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • HIV Infections
  • HIV-1
  • Humans
  • Molecular Sequence Data
  • Neutralization Tests
  • Protein Engineering
  • Recombinant Proteins
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Identity

PubMed Central ID

  • PMC2965066

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.1187659

PubMed ID

  • 20616233
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Additional Document Info

start page

  • 856

end page

  • 861

volume

  • 329

issue

  • 5993

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