Journal article

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

  • Corti, Davide Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Langedijk, Johannes P. M. Pepscan Therapeutics BV, Lelystad, Netherlands
  • Hinz, Andreas Unit for Virus Host Cell Interaction, Grenoble, France
  • Seaman, Michael S. Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America
  • Vanzetta, Fabrizia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Fernandez-Rodriguez, Blanca M. Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Silacci, Chiara Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Pinna, Debora Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Jarrossay, David Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Balla-Jhagjhoorsingh, Sunita Institute of Tropical Medicine, Antwerp, Belgium
  • Willems, Betty Institute of Tropical Medicine, Antwerp, Belgium
  • Zekveld, Maria J. Pepscan Therapeutics BV, Lelystad, Netherlands
  • Dreja Hanna
  • O’Sullivan, Eithne Queen Mary University, London, United Kingdom
  • Pade, Corinna Queen Mary University, London, United Kingdom
  • Orkin, Chloe Barts and the London NHS Trust, London, United Kingdom
  • Jeffs, Simon A. Department of Infectious Diseases, The Wright-Fleming Institute, Imperial College Faculty of Medicine, London, United Kingdom
  • Montefiori, David C. Duke University Medical Center, Durham, North Carolina, United States of America
  • David, Davis Department of Virology, Biomedical Primate Research Centre, Rijswijk, Netherlands
  • Weissenhorn, Winfried Unit for Virus Host Cell Interaction, Grenoble, France
  • McKnight, Aine Queen Mary University, London, United Kingdom
  • Heeney, Jonathan L. Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
  • Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Sattentau, Quentin J. The Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
  • Weiss, robin A. Division of Infection and Immunity, University College London, London, United Kingdom
  • Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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    20.01.2010
Published in:
  • Plos one. - 2010, vol. 5, no. 1, p. e8805
English 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.
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  • English
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Medicine
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https://susi.usi.ch/usi/documents/318907
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