Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.
Abstract
Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied
the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated
HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb)
that targets a conserved glycan patch on Env of geographically diverse HIV-1 strains
using a unique heavy-chain (VH) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization.
Here, we describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive bnAbs without VH-swapped domains from simian-human immunodeficiency virus (SHIV)-infected macaques.
FDG Abs also recognized cell-surface glycans on diverse pathogens, including yeast
and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike. FDG precursors
were expanded by glycan-bearing immunogens in macaques and were abundant in HIV-1-naive
humans. Moreover, FDG precursors were predominately mutated IgM+IgD+CD27+, thus suggesting that they originated from a pool of antigen-experienced IgM+ or marginal zone B cells.
Type
Journal articleSubject
FDG AbsFab dimerization
HIV-1 Env glycans
IgM-memory B cells
SARS-CoV-2 spike glycans
glycan-dependent Ab binding
marginal zone B cells
natural Abs
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https://hdl.handle.net/10161/23224Published Version (Please cite this version)
10.1016/j.cell.2021.04.042Publication Info
(2021). Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.
Cell, 184(11). pp. 2955-2972.e25. 10.1016/j.cell.2021.04.042. Retrieved from https://hdl.handle.net/10161/23224.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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Priyamvada Acharya
Associate Professor in Surgery
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
Alberto Bartesaghi
Associate Professor of Computer Science
Mario-Juan Borgnia
Adjunct Professor in the Department of Biochemistry
Sophie Gobeil
Research Associate, Senior
Duke Human Vaccine Institute, Acharya Lab, Division of Structural Biology
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
Rory Henderson
Assistant Professor in Medicine
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,
Ryan Meyerhoff
House Staff
Program Start Year: 2013Barton Haynes Laboratory"Studies of Immunogens to Induce
Broadly Neutralizing HIV Antibodies"
David Charles Montefiori
Professor in Surgery
Dr. Montefiori is Professor and Director of the Laboratory for HIV and COVID-19 Vaccine
Research & Development in the Department of Surgery, Division of Surgical Sciences
at Duke University Medical Center. His major research interests are viral immunology
and HIV and COVID-19 vaccine development, with a special emphasis on neutralizing
antibodies. Multiple aspects of HIV-1 neutralizing antibodies are studied in his laboratory,
including mechanisms of neutralization and escape,
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
John Robert Perfect
James B. Duke Distinguished Professor of Medicine
Research in my laboratory focuses around several aspects of medical mycology. We
are investigating antifungal agents (new and old) in animal models of candida and
cryptococcal infections. We have examined clinical correlation of in vitro antifungal
susceptibility testing and with in vivo outcome. Our basic science project examines
the molecular pathogenesis of cryptococcal infections. We have developed a molecular
foundation for C. neoformans, including transformation systems, gene disr
Kevin O'Neil Saunders
Associate Professor in Surgery
The Saunders laboratory aims to understand the immunology of HIV-1 antibodies and
the molecular biology of their interaction with HIV-1 envelope (Env) glycoprotein.
Our overall goal is to develop protective antibody-based vaccines; therefore, the
laboratory has two sections–antibody repertoire analysis and immunogen design.
Our research premise is that vaccine-elicited antibodies will broadly neutralize HIV-1
if they can bind directly to the host glycans on Env. However, Env glycans are
Gregory David Sempowski
Professor in Medicine
Dr. Sempowski earned his PhD in Immunology from the University of Rochester and was
specifically trained in the areas of inflammation, wound healing, and host response
(innate and adaptive). Dr. Sempowski contributed substantially to the field of lung
inflammation and fibrosis defining the roles of pulmonary fibroblast heterogeneity
and CD40/CD40L signaling in regulating normal and pathogenic lung inflammation. During
his postdoctoral training with Dr. Barton F. H
Kevin J Wiehe
Associate Professor in Medicine
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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