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Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.

dc.contributor.author Corti, Davide
dc.contributor.author Langedijk, Johannes PM
dc.contributor.author Hinz, Andreas
dc.contributor.author Seaman, Michael S
dc.contributor.author Vanzetta, Fabrizia
dc.contributor.author Fernandez-Rodriguez, Blanca M
dc.contributor.author Silacci, Chiara
dc.contributor.author Pinna, Debora
dc.contributor.author Jarrossay, David
dc.contributor.author Balla-Jhagjhoorsingh, Sunita
dc.contributor.author Willems, Betty
dc.contributor.author Zekveld, Maria J
dc.contributor.author Dreja, Hanna
dc.contributor.author O'Sullivan, Eithne
dc.contributor.author Pade, Corinna
dc.contributor.author Orkin, Chloe
dc.contributor.author Jeffs, Simon A
dc.contributor.author Montefiori, David C
dc.contributor.author Davis, David
dc.contributor.author Weissenhorn, Winfried
dc.contributor.author McKnight, Aine
dc.contributor.author Heeney, Jonathan L
dc.contributor.author Sallusto, Federica
dc.contributor.author Sattentau, Quentin J
dc.contributor.author Weiss, Robin A
dc.contributor.author Lanzavecchia, Antonio
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:31:27Z
dc.date.issued 2010-01-20
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/20098712
dc.identifier.uri https://hdl.handle.net/10161/4523
dc.description.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.
dc.language eng
dc.language.iso en_US
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0008805
dc.subject Amino Acid Sequence
dc.subject Antibodies, Monoclonal
dc.subject Antibodies, Neutralizing
dc.subject Antigens, CD4
dc.subject B-Lymphocytes
dc.subject Binding Sites, Antibody
dc.subject Epitopes
dc.subject HIV Infections
dc.subject HIV-1
dc.subject Humans
dc.subject Immunologic Memory
dc.subject Molecular Sequence Data
dc.title Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.
dc.title.alternative
dc.type Journal article
duke.contributor.id Montefiori, David C|0099412
dc.description.version Version of Record
duke.date.pubdate 2010-1-20
duke.description.issue 1
duke.description.volume 5
dc.relation.journal Plos One
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/20098712
pubs.begin-page e8805
pubs.issue 1
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Human Vaccine Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Surgical Sciences
pubs.publication-status Published online
pubs.volume 5
dc.identifier.eissn 1932-6203
duke.contributor.orcid Montefiori, David C|0000-0003-0856-6319


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