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

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TitleRational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1.
Publication TypeJournal Article
Year of Publication2010
AuthorsWu, 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
JournalScience
Volume329
Issue5993
Pagination856-61
Date Published2010 Aug 13
ISSN1095-9203
KeywordsAIDS 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
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.

DOI10.1126/science.1187659
Alternate JournalScience
PubMed ID20616233
PubMed Central IDPMC2965066
Grant ListZ99 AI999999 / AI / NIAID NIH HHS / United States