Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.
Abstract
BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a
broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing
antibody B cell response to HIV-1 infection are important goals that are central to
the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized
IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected
on the basis of plasma neutralization profiles that were cross-clade and relatively
potent. Culture supernatants were screened using various recombinant forms of the
envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that
were mapped to different Env surfaces, most of which showed neutralizing activity.
One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding
site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses,
and demonstrated reactivity that was comparable in breadth, but distinct in neutralization
specificity, to that of the other CD4 binding site-specific neutralizing mAb b12.
A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all
Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third
mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized
a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent
selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate
screening methods, a large proportion of memory B cells can be isolated that produce
mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of
neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies
with potential for passive protection and template-based vaccine design.
Type
Journal articleSubject
Amino Acid SequenceAntibodies, Monoclonal
Antibodies, Neutralizing
Antigens, CD4
B-Lymphocytes
Binding Sites, Antibody
Epitopes
HIV Infections
HIV-1
Humans
Immunologic Memory
Molecular Sequence Data
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https://hdl.handle.net/10161/4523Published Version (Please cite this version)
10.1371/journal.pone.0008805Publication Info
Balla-Jhagjhoorsingh, S; Corti, D; Davis, D; Dreja, H; Fernandez-Rodriguez, BM; Heeney,
JL; ... Zekveld, MJ (2010). Analysis of memory B cell responses and isolation of novel monoclonal antibodies with
neutralizing breadth from HIV-1-infected individuals. PLoS One, 5(1). pp. e8805. 10.1371/journal.pone.0008805. Retrieved from https://hdl.handle.net/10161/4523.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
David Charles Montefiori
Professor of 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

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