Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1

• Published in: Science (American Association for the Advancement of Science) Vol. 329; no. 5993; pp. 856 - 861
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 13.08.2010; The American Association for the Advancement of Science
• Subjects: AIDS Vaccines; Amino acids; Antibodies; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - isolation & purification; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - isolation & purification; Antibody Specificity; B lymphocytes; B-Lymphocytes - immunology; Binding; Binding Sites, Antibody; CD4 Antigens - immunology; CD4 Antigens - metabolism; Circulating; Cross Reactions; Drug Design; Envelopes; Enzyme linked immunosorbent assay; Epitopes - immunology; Genes; Genes, Immunoglobulin Heavy Chain; Genes, Immunoglobulin Light Chain; Glycoprotein; Glycoproteins; HIV; HIV 1; HIV Antibodies - immunology; HIV Antibodies - isolation & purification; HIV Envelope Protein gp120 - chemistry; HIV Envelope Protein gp120 - immunology; HIV Envelope Protein gp120 - metabolism; HIV infections; HIV Infections - immunology; HIV Infections - virology; HIV-1 - genetics; HIV-1 - immunology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; immunoglobulin genes; Immunoglobulins; Immunology; Infectious diseases; Molecular Sequence Data; Monoclonal antibodies; Neutralization; Neutralization Tests; Neutralizing; neutralizing antibodies; Protein Engineering; Proteins; Reactivity; Recombinant Proteins - chemistry; Recombinant Proteins - immunology; Recombinant Proteins - metabolism; Research facilities; Vaccines; Viruses
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1187659

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.