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

Hua-Xin Liao (), Rebecca Lynch, Tongqing Zhou, Feng Gao, S. Munir Alam, Scott D. Boyd, Andrew Z. Fire, Krishna M. Roskin, Chaim A. Schramm, Zhenhai Zhang, Jiang Zhu, Lawrence Shapiro, James C. Mullikin, S. Gnanakaran, Peter Hraber, Kevin Wiehe, Garnett Kelsoe, Guang Yang, Shi-Mao Xia, David C. Montefiori, Robert Parks, Krissey E. Lloyd, Richard M. Scearce, Kelly A. Soderberg, Myron Cohen, Gift Kamanga, Mark K. Louder, Lillian M. Tran, Yue Chen, Fangping Cai, Sheri Chen, Stephanie Moquin, Xiulian Du, M. Gordon Joyce, Sanjay Srivatsan, Baoshan Zhang, Anqi Zheng, George M. Shaw, Beatrice H. Hahn, Thomas B. Kepler, Bette T. M. Korber, Peter D. Kwong, John R. Mascola and Barton F. Haynes ()
Additional contact information
Hua-Xin Liao: Duke University Human Vaccine Institute, Duke University School of Medicine
Rebecca Lynch: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Tongqing Zhou: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Feng Gao: Duke University Human Vaccine Institute, Duke University School of Medicine
S. Munir Alam: Duke University Human Vaccine Institute, Duke University School of Medicine
Scott D. Boyd: Stanford University
Andrew Z. Fire: Stanford University
Krishna M. Roskin: Stanford University
Chaim A. Schramm: Columbia University
Zhenhai Zhang: Columbia University
Jiang Zhu: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Lawrence Shapiro: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
James C. Mullikin: NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health
S. Gnanakaran: Los Alamos National Laboratory
Peter Hraber: Los Alamos National Laboratory
Kevin Wiehe: Duke University Human Vaccine Institute, Duke University School of Medicine
Garnett Kelsoe: Duke University Human Vaccine Institute, Duke University School of Medicine
Guang Yang: Duke University Human Vaccine Institute, Duke University School of Medicine
Shi-Mao Xia: Duke University Human Vaccine Institute, Duke University School of Medicine
David C. Montefiori: Duke University Human Vaccine Institute, Duke University School of Medicine
Robert Parks: Duke University Human Vaccine Institute, Duke University School of Medicine
Krissey E. Lloyd: Duke University Human Vaccine Institute, Duke University School of Medicine
Richard M. Scearce: Duke University Human Vaccine Institute, Duke University School of Medicine
Kelly A. Soderberg: Duke University Human Vaccine Institute, Duke University School of Medicine
Myron Cohen: Epidemiology and Microbiology and Immunology, University of North Carolina
Gift Kamanga: University of North Carolina Project, Kamuzu Central Hospital
Mark K. Louder: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Lillian M. Tran: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Yue Chen: Duke University Human Vaccine Institute, Duke University School of Medicine
Fangping Cai: Duke University Human Vaccine Institute, Duke University School of Medicine
Sheri Chen: Duke University Human Vaccine Institute, Duke University School of Medicine
Stephanie Moquin: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Xiulian Du: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
M. Gordon Joyce: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Sanjay Srivatsan: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Baoshan Zhang: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Anqi Zheng: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
George M. Shaw: Perelman School of Medicine, University of Pennsylvania
Beatrice H. Hahn: Perelman School of Medicine, University of Pennsylvania
Thomas B. Kepler: Boston University
Bette T. M. Korber: Los Alamos National Laboratory
Peter D. Kwong: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
John R. Mascola: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Barton F. Haynes: Duke University Human Vaccine Institute, Duke University School of Medicine

Nature, 2013, vol. 496, issue 7446, 469-476

Abstract: 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.

Date: 2013
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DOI: 10.1038/nature12053

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