Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.
Abstract
Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env)
in distinctive patterns, in some cases acquiring substantial breadth. We report that
primary HIV-1 envelope proteins-when expressed by simian-human immunodeficiency viruses
in rhesus macaques-elicited patterns of Env-antibody coevolution strikingly similar
to those in humans. This included conserved immunogenetic, structural and chemical
solutions to epitope recognition and precise Env-am ino acid substitutions, insertions
and deletions leading to virus persistence. The structure of one rhesus antibody,
capable of neutralizing 49% of a 208-strain panel, revealed a V2-apex mode of recognition
like that of human bNAbs PGT145/PCT64-35S. Another rhesus antibody bound the CD4-binding
site by CD4 mimicry mirroring human bNAbs 8ANC131/CH235/VRC01. Virus-antibody coevolution
in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding
HIV-1 immunogen design.
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https://hdl.handle.net/10161/21823Published Version (Please cite this version)
10.1126/science.abd2638Publication Info
(2020). Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization
breadth. Science (New York, N.Y.). pp. eabd2638-eabd2638. 10.1126/science.abd2638. Retrieved from https://hdl.handle.net/10161/21823.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
Mattia Bonsignori
Associate Professor in Medicine
HIV vaccine development Study of B-cell immune responses in HIV positive individuals
Determination of correlates of protective immunity to HIV Induction of broadly neutralizing
antibodies to HIV Development of multiplex functional assays for the evaluation at
a single-cell level of B-cell responses to vaccinations, infections and in vitro stimulation
Epidemiology and characterization of bacterial resistance determinants (past) </do
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
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,
Michael Anthony Moody
Professor of Pediatrics
Tony Moody, MD is a Professor in the Department of Pediatrics, Division of Infectious
Diseases and Professor in the Department of Integrative Immunobiology at Duke University
Medical Center. Research in the Moody lab is focused on understanding the B cell responses
during infection, vaccination, and disease. The lab has become a resource for human
phenotyping, flow characterization, staining and analysis at the Duke Human Vaccine
Institute (DHVI). The Moody lab is currently funded to study in
Kevin O'Neil Saunders
Associate Professor in Surgery
Dr. Kevin O. Saunders graduated from Davidson College in 2005 with a bachelor of science
in biology. At Davidson College, he trained in the laboratory of Dr. Karen Hales identifying
the genetic basis of infertility. Dr. Saunders completed his doctoral research on
CD8+ T cell immunity against HIV-1 infection with Dr. Georgia Tomaras at Duke University
in 2010. He subsequently trained as a postdoctoral fellow in the laboratories of Drs.
Gary Nabel and John Mascola at the National Institutes of
Kevin J Wiehe
Norman L. Letvin Associate Professor in Medicine
Dr. Kevin Wiehe is the associate director of research, director of computational biology
and co-director of the Quantitative Research Division at the Duke Human Vaccine Institute
(DHVI). He has over 20 years of experience in the field of computational biology and
has expertise in computational structural biology, computational genomics, and computational
immunology.
For the past decade, he has applied his unique background to developing computational
approaches for studying the B cell
Wilton Bryan Williams
Associate Professor in Surgery
Dr. Williams completed a PhD in Biomedical Sciences (Immunology and Microbiology)
from the University of Florida and did his postdoctoral work in the laboratory of
Dr. Barton Haynes at the Duke Human Vaccine Institute (DHVI). The key goals of HIV
vaccine development are to define the host-virus events during natural HIV infection
that lead to the induction of broadly neutralizing antibodies, and to recreate those
events with a vaccine. As a junior faculty member in the DHVI, Dr. W
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