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

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dc.contributor.author Corti, D.
dc.contributor.author Langedijk, J. P. M.
dc.contributor.author Hinz, A.
dc.contributor.author Seaman, M. S.
dc.contributor.author Vanzetta, F.
dc.contributor.author Fernandez-Rodriguez, B. M.
dc.contributor.author Silacci, C.
dc.contributor.author Pinna, D.
dc.contributor.author Jarrossay, D.
dc.contributor.author Balla-Jhagjhoorsingh, S.
dc.contributor.author Willems, B.
dc.contributor.author Zekveld, M. J.
dc.contributor.author Dreja, H.
dc.contributor.author O'Sullivan, E.
dc.contributor.author Pade, C.
dc.contributor.author Orkin, C.
dc.contributor.author Jeffs, S. A.
dc.contributor.author Montefiori, D. C.
dc.contributor.author Davis, D.
dc.contributor.author Weissenhorn, W.
dc.contributor.author McKnight, A.
dc.contributor.author Heeney, J. L.
dc.contributor.author Sallusto, F.
dc.contributor.author Sattentau, Q. J.
dc.contributor.author Weiss, R. A.
dc.contributor.author Lanzavecchia, A.
dc.date.accessioned 2010-02-09T09:07:08Z
dc.date.available 2010-02-09T09:07:08Z
dc.date.issued 2010
dc.identifier.issn 1932-6203
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0008805
dc.identifier.other ITG-M10B
dc.identifier.other ITG-M11B
dc.identifier.other MICRO
dc.identifier.other U-VIROL
dc.identifier.other DOI
dc.identifier.other ELECTRONIC
dc.identifier.other UPD18
dc.identifier.other FTA
dc.identifier.other ABSTRACT
dc.identifier.uri http://hdl.handle.net/10390/2910
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. en
dc.language English en
dc.subject Viral diseases en
dc.subject HIV-1 en
dc.subject AIDS en
dc.subject Screening en
dc.subject Isolation en
dc.subject Monoclonal antibodies en
dc.subject B-cells en
dc.subject Memory cells en
dc.subject Characterization en
dc.subject IgG en
dc.subject Neutralizing antibodies en
dc.subject Epitopes en
dc.title Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals en
dc.type Article-E en
dc.citation.issue 1 en
dc.citation.jtitle PLoS ONE en
dc.citation.volume 5 en
dc.citation.pages e8805 en
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/20098712
dc.citation.jabbreviation PLoS ONE en


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