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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
    Alam, S Munir
    Boyd, SD
    Cai, Fangping
    Chen, S
    Chen, Y
    Cohen, M
    Du, X
    Fire, AZ
    Gao, Feng
    Gnanakaran, S
    Hahn, Beatrice H
    Haynes, Barton Ford
    Hraber, Peter T
    Joyce, MG
    Kamanga, G
    Kelsoe, Garnett
    Kepler, TB
    Korber, Bette T
    Kwong, PD
    Liao, Hua-Xin
    Lloyd, KE
    Louder, MK
    Lynch, R
    Mascola, JR
    Montefiori, David Charles
    Moquin, S
    Mullikin, JC
    NISC Comparative Sequencing Program
    Parks, Robert
    Roskin, KM
    Scearce, Richard
    Schramm, CA
    Shapiro, Lawrence
    Shaw, GM
    Soderberg, Kelly
    Srivatsan, S
    Tran, LM
    Wiehe, K
    Xia, Shi-Mao
    Yang, G
    Zhang, B
    Zhang, Z
    Zheng, A
    Zhou, T
    Zhu, Jiang
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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
    Alam, S Munir; Boyd, SD; Cai, Fangping; Chen, S; Chen, Y; Cohen, M; ... Zhu, Jiang (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 of 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 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 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 of 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

    Assistant Professor in Medicine
    Zhu

    Jason Zhu

    House Staff
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