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Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Liao, Hua-Xin Lynch, Rebecca Zhou, Tongqing Gao, Feng Alam, S Munir Boyd, Scott D Fire, Andrew Z Roskin, Krishna M Schramm, Chaim A Zhang, Zhenhai Zhu, Jiang Shapiro, Lawrence NISC Comparative Sequencing Program Mullikin, James C Gnanakaran, S Hraber, Peter Wiehe, Kevin Kelsoe, Garnett Yang, Guang Xia, Shi-Mao Montefiori, David C Parks, Robert Lloyd, Krissey E Scearce, Richard M Soderberg, Kelly A Cohen, Myron Kamanga, Gift Louder, Mark K Tran, Lillian M Chen, Yue Cai, Fangping Chen, Sheri Moquin, Stephanie Du, Xiulian Joyce, M Gordon Srivatsan, Sanjay Zhang, Baoshan Zheng, Anqi Shaw, George M Hahn, Beatrice H Kepler, Thomas B Korber, Bette TM Kwong, Peter D Mascola, John R Haynes, Barton F
dc.coverage.spatial England 2015-11-18T16:39:50Z 2013-04-25
dc.identifier nature12053
dc.description.abstract Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination.
dc.language eng
dc.publisher Springer Science and Business Media LLC
dc.relation.ispartof Nature
dc.relation.isversionof 10.1038/nature12053
dc.subject AIDS Vaccines
dc.subject Africa
dc.subject Amino Acid Sequence
dc.subject Antibodies, Monoclonal
dc.subject Antibodies, Neutralizing
dc.subject Antigens, CD4
dc.subject Cell Lineage
dc.subject Cells, Cultured
dc.subject Clone Cells
dc.subject Cross Reactions
dc.subject Crystallography, X-Ray
dc.subject Epitopes
dc.subject Evolution, Molecular
dc.subject HIV Antibodies
dc.subject HIV Envelope Protein gp120
dc.subject HIV-1
dc.subject Humans
dc.subject Models, Molecular
dc.subject Molecular Sequence Data
dc.subject Mutation
dc.subject Neutralization Tests
dc.subject Phylogeny
dc.subject Protein Structure, Tertiary
dc.title Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.
dc.type Journal article Liao, Hua-Xin|0107020 Gao, Feng|0285306 Alam, S Munir|0251502 Wiehe, Kevin|0451680 Kelsoe, Garnett|0205291 Montefiori, David C|0099412 Haynes, Barton F|0114780
pubs.begin-page 469
pubs.end-page 476
pubs.issue 7446
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Human Vaccine Institute
pubs.organisational-group Global Health Institute
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Duke Human Vaccine Institute
pubs.organisational-group Medicine, Infectious Diseases
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Surgical Sciences Section for AIDS Research & Development
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published
pubs.volume 496
dc.identifier.eissn 1476-4687
duke.contributor.orcid Gao, Feng|0000-0001-8903-0203
duke.contributor.orcid Montefiori, David C|0000-0003-0856-6319

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