Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.
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.We i...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2808385?pdf=render |
| _version_ | 1819053088852410368 |
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| author | Davide Corti Johannes P M Langedijk Andreas Hinz Michael S Seaman Fabrizia Vanzetta Blanca M Fernandez-Rodriguez Chiara Silacci Debora Pinna David Jarrossay Sunita Balla-Jhagjhoorsingh Betty Willems Maria J Zekveld Hanna Dreja Eithne O'Sullivan Corinna Pade Chloe Orkin Simon A Jeffs David C Montefiori David Davis Winfried Weissenhorn Aine McKnight Jonathan L Heeney Federica Sallusto Quentin J Sattentau Robin A Weiss Antonio Lanzavecchia |
| author_facet | Davide Corti Johannes P M Langedijk Andreas Hinz Michael S Seaman Fabrizia Vanzetta Blanca M Fernandez-Rodriguez Chiara Silacci Debora Pinna David Jarrossay Sunita Balla-Jhagjhoorsingh Betty Willems Maria J Zekveld Hanna Dreja Eithne O'Sullivan Corinna Pade Chloe Orkin Simon A Jeffs David C Montefiori David Davis Winfried Weissenhorn Aine McKnight Jonathan L Heeney Federica Sallusto Quentin J Sattentau Robin A Weiss Antonio Lanzavecchia |
| author_sort | Davide Corti |
| collection | DOAJ |
| description | 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.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.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. |
| first_indexed | 2024-12-21T12:30:10Z |
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| id | doaj.art-1e6dbd71d67b44808b1c11781a2ed731 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T12:30:10Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-1e6dbd71d67b44808b1c11781a2ed7312022-12-21T19:04:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0151e880510.1371/journal.pone.0008805Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.Davide CortiJohannes P M LangedijkAndreas HinzMichael S SeamanFabrizia VanzettaBlanca M Fernandez-RodriguezChiara SilacciDebora PinnaDavid JarrossaySunita Balla-JhagjhoorsinghBetty WillemsMaria J ZekveldHanna DrejaEithne O'SullivanCorinna PadeChloe OrkinSimon A JeffsDavid C MontefioriDavid DavisWinfried WeissenhornAine McKnightJonathan L HeeneyFederica SallustoQuentin J SattentauRobin A WeissAntonio LanzavecchiaThe 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.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.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.http://europepmc.org/articles/PMC2808385?pdf=render |
| spellingShingle | Davide Corti Johannes P M Langedijk Andreas Hinz Michael S Seaman Fabrizia Vanzetta Blanca M Fernandez-Rodriguez Chiara Silacci Debora Pinna David Jarrossay Sunita Balla-Jhagjhoorsingh Betty Willems Maria J Zekveld Hanna Dreja Eithne O'Sullivan Corinna Pade Chloe Orkin Simon A Jeffs David C Montefiori David Davis Winfried Weissenhorn Aine McKnight Jonathan L Heeney Federica Sallusto Quentin J Sattentau Robin A Weiss Antonio Lanzavecchia Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals. PLoS ONE |
| title | Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals. |
| title_full | Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals. |
| title_fullStr | Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals. |
| title_full_unstemmed | Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals. |
| title_short | Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals. |
| title_sort | analysis of memory b cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from hiv 1 infected individuals |
| url | http://europepmc.org/articles/PMC2808385?pdf=render |
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