Scientific Publication

Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing

author(s) Burton, D.R.. - Kapiga, S.H.. - Koff, W.C.. - McKee, K.. - Kwong, P.D.. - Mascola, J.R.. - Schmidt, S.D.. - Nabel, G.J.. - Haynes, B.F.. - O'Dell, S.. - Bonsignori, M.. - Chen XueJun, Connors. - M., Crump. - J.A., Doria-Rose. - N.A., Georgiev. - I., Jiang Zhu. - Lan Wu, Longo. - Nn.S., Louder. - M., Mullikin. - J.C., Perfetto. - S., Roederer. - M., Sam. - N.E., Shapiro. - L., Simek. - M., Wang. - C., Wei Shi. - Wu XueLing, Yang YongPing. - Yang ZhiYong, Yang ZhongJia. - Zhang BaoShan, Zhang ZhenHai.
from UK Foreign, Commonwealth & Development Office (FCDO)
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Wu XueLing; Zhou Tongqing; Jiang Zhu; Zhang BaoShan; Georgiev, I.; Wang, C.; Chen XueJun; Longo, NN.S.; Louder, M.; McKee, K.; O’Dell, S.; Perfetto, S.; Schmidt, S.D.; Wei Shi; Lan Wu; Yang YongPing; Yang ZhiYong; Yang ZhongJia; Zhang ZhenHai; Bonsignori, M.; Crump, J.A.; Kapiga, S.H.; Sam, N.E.; Haynes, B.F.; Simek, M.; Burton, D.R.; Koff, W.C.; Doria-Rose, N.A.; Connors, M.; Mullikin, J.C.; Nabel, G.J.; Roederer, M.; Shapiro, L.; Kwong, P.D.; Mascola, J.R. . Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science (2011) 333 (6049) 1593-1602. (DOI: 10.1126/science.1207532)

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Abstract

Antibody VRC01 is a human immunoglobulin that neutralizes about 90% of HIV-1 isolates. To understand how such broadly neutralizing antibodies develop, we used x-ray crystallography and 454 pyrosequencing to characterize additional VRC01-like antibodies from HIV-1–infected individuals. Crystal structures revealed a convergent mode of binding for diverse antibodies to the same CD4-binding-site epitope. A functional genomics analysis of expressed heavy and light chains revealed common pathways of antibody-heavy chain maturation, confined to the IGHV1-2*02 lineage, involving dozens of somatic changes, and capable of pairing with different light chains. Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies thus involves the evolution of antibodies to a highly affinity-matured state required to recognize an invariant viral structure, with lineages defined from thousands of sequences providing a genetic roadmap of their development

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