Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.
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 articleSubject
AIDS VaccinesAfrica
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
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https://hdl.handle.net/10161/10902Published Version (Please cite this version)
10.1038/nature12053Publication Info
(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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Show full item recordScholars@Duke
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
Feng Gao
Professor Emeritus in 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 Distinguished 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 Distinguished 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 in 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
Kevin J Wiehe
Associate Professor in Medicine
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