1. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus
- Author
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Barton F. Haynes, Nisc Comparative Sequencing Program, John R. Mascola, Chaim A. Schramm, Krissey E. Lloyd, Robert Parks, Xiulian Du, Jiang Zhu, Lillian Tran, James C. Mullikin, Peter T. Hraber, Richard M. Scearce, Lawrence Shapiro, Shi-Mao Xia, Hua-Xin Liao, Peter D. Kwong, Fangping Cai, Zhenhai Zhang, Garnett Kelsoe, Sandrasegaram Gnanakaran, Feng Gao, Myron S. Cohen, Beatrice H. Hahn, M. Gordon Joyce, Anqi Zheng, Kevin Wiehe, Baoshan Zhang, Scott D. Boyd, Sanjay Srivatsan, Andrew Fire, Stephanie Moquin, Mark K. Louder, Guang Yang, S. Munir Alam, Gift Kamanga, Tongqing Zhou, Thomas B. Kepler, David C. Montefiori, Yue Chen, Bette T. Korber, Krishna M. Roskin, George M. Shaw, Rebecca M. Lynch, Kelly A. Soderberg, and Sheri Chen
- Subjects
Models, Molecular ,Molecular Sequence Data ,Cross Reactions ,HIV Antibodies ,HIV Envelope Protein gp120 ,Crystallography, X-Ray ,medicine.disease_cause ,Epitope ,Virus ,Neutralization ,Article ,Evolution, Molecular ,Epitopes ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Neutralization Tests ,medicine ,Humans ,Cell Lineage ,Amino Acid Sequence ,Cells, Cultured ,Phylogeny ,030304 developmental biology ,AIDS Vaccines ,0303 health sciences ,Mutation ,Multidisciplinary ,biology ,Antibodies, Monoclonal ,Antibodies, Neutralizing ,Virology ,Clone Cells ,Protein Structure, Tertiary ,3. Good health ,Vaccination ,Viral evolution ,Africa ,CD4 Antigens ,HIV-1 ,biology.protein ,Antibody ,030217 neurology & neurosurgery - 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.
- Published
- 2013