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

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

doi:10.1038/nature12053

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.

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 http://hdl.handle.net/10161/10902.

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Scholars@Duke

S. Munir Alam

Professor in Medicine

Research Interests. Biophysical analysis of coreceptor modulation of TCR-MHC interactions. One of our research interests is to study the molecular mechanisms of T cell recognition. We have particular interest in understanding the trimolecular interactions between membrane bound T cell receptor (TCR-CD3 complex) and its ligand, the peptide-MHC complex (pMHC), and co-receptor molecules. We are using different biophysical approaches which include surface plasmon resonance, isothermal titr

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.

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

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,

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

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