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Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.

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Date
2013-04-25
Authors
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
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(45 total)
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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.
Type
Journal article
Subject
AIDS Vaccines
Africa
Amino Acid Sequence
Antibodies, Monoclonal
Antibodies, Neutralizing
Antigens, CD4
Cell Lineage
Cells, Cultured
Clone Cells
Cross Reactions
Crystallography, X-Ray
Epitopes
Evolution, Molecular
HIV Antibodies
HIV Envelope Protein gp120
HIV-1
Humans
Models, Molecular
Molecular Sequence Data
Mutation
Neutralization Tests
Phylogeny
Protein Structure, Tertiary
Permalink
https://hdl.handle.net/10161/10902
Published Version (Please cite this version)
10.1038/nature12053
Publication Info
Liao, Hua-Xin; Lynch, Rebecca; Zhou, Tongqing; Gao, Feng; Alam, S Munir; Boyd, Scott D; ... Haynes, Barton F (2013). Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature, 496(7446). pp. 469-476. 10.1038/nature12053. Retrieved from https://hdl.handle.net/10161/10902.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Alam

S. Munir Alam

Professor in Medicine
Research Interests.  The Alam laboratory’s primary research is focused on understanding the biophysical properties of antigen-antibody binding and the molecular events of early B cell activation using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events for their activation. In the lon
Gao

Feng Gao

Professor Emeritus in Medicine
Dr. Feng Gao is Professor of Medicine at Duke University. The Gao laboratory has a long-standing interest in elucidating the origins and evolution of human and simian inmmunodeficiency viruses (HIV and SIV), and in studying HIV/SIV gene function and pathogenic mechanisms from the evolutionary perspective. These studies have led to new strategies to better understand HIV origins,  biology, pathogenesis and drug resistance, and to design new AIDS vaccines.
Haynes

Barton Ford Haynes

Frederic M. Hanes Distinguished Professor of Medicine
The Haynes lab is studying host innate and adaptive immune responses to the human immunodeficiency virus (HIV), tuberculosis (TB), and influenza in order to find the enabling technology to make preventive vaccines against these three major infectious diseases. Mucosal Immune Responses in Acute HIV Infection The Haynes lab is working to determine why broadly neutralizing antibodies are rarely made in acute HIV infection (AHI), currently a major obstacle in the de
Kelsoe

Garnett H. Kelsoe

James B. Duke Distinguished Professor of Immunology
1. Lymphocyte development and antigen-driven diversification of immunoglobulin and T cell antigen receptor genes. 2. The germinal center reaction and mechanisms for clonal selection and self - tolerance. The origins of autoimmunity. 3. Interaction of innate- and adaptive immunity and the role of inflammation in lymphoid organogenesis. 4. The role of secondary V(D)J gene rearrangment in lymphocyte development and malignancies. 5. Mathematical modeling of immune responses,
Liao

Hua-Xin Liao

Adjunct Professor in the Department of Medicine
Dr. Liao is a Professor of Medicine and Research Director of Duke Human Vaccine Institute. Dr. Liao is a MD virologistt rained in China. In early 1980’s, Dr. Liao made major contributions to the first isolation of epidemic hemorrhagic fever virus (hataanvirus) from Apodemus agraius using tissue culture in China. The successful identification and isolation of Hataanvirus enabled the early diagnosis and treatment of the disease, and advancement of HFRS research towards prevention by de
Montefiori

David Charles Montefiori

Professor in Surgery
Dr. Montefiori is Professor and Director of the Laboratory for AIDS Vaccine Research and Development in the Department of Surgery, Division of Surgical Sciences, Duke University Medical Center. His major research interests are viral immunology and AIDS vaccine development, with a special emphasis on neutralizing antibodies. One of his highest priorities is to identify immunogens that generate broadly cross-reactive neutralizing antibodies for inclusion in HIV vaccines.  Many aspects of the
Wiehe

Kevin J Wiehe

Associate Professor in Medicine
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