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

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

England

2015-11-18T16:39:50Z

2013-04-25

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.

http://www.ncbi.nlm.nih.gov/pubmed/23552890

nature12053

1476-4687

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

eng

Springer Science and Business Media LLC

Nature

10.1038/nature12053

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

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

Journal article

Gao, Feng|0000-0001-8903-0203

Alam, S Munir|0000-0003-0941-0703

Kelsoe, Garnett|0000-0002-8770-040X

Montefiori, David C|0000-0003-0856-6319

http://www.ncbi.nlm.nih.gov/pubmed/23552890

469

476

7446

Basic Science Departments

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Human Vaccine Institute

Global Health Institute

Immunology

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Duke Human Vaccine Institute

Medicine, Infectious Diseases

Pathology

School of Medicine

Surgery

Surgery, Surgical Sciences Section for AIDS Research & Development

University Institutes and Centers

Published

496