Journal article

Characterization of neutralizing profiles in HIV-1 infected patients from whom the HJ16, HGN194 and HK20 mAbs were obtained

  • Balla-Jhagjhoorsingh, Sunita S. Institute of Tropical Medicine, Antwerp, Belgium
  • Willems, Betty Institute of Tropical Medicine, Antwerp, Belgium
  • Heyndrickx, Liesbeth Institute of Tropical Medicine, Antwerp, Belgium
  • Heyndrickx, Leo Institute of Tropical Medicine, Antwerp, Belgium
  • Vereecken, Katleen Institute of Tropical Medicine, Antwerp, Belgium
  • Janssens, Wouter Institute of Tropical Medicine, Antwerp, Belgium
  • Seaman, Michael S. Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America
  • Corti, Davide Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Davis, David Biomedical Primate Research Centre, Rijswijk, the Netherlands
  • Vanham, Guido Institute of Tropical Medicine, Antwerp, Belgium - Department of Biomedical Sciences, University of Antwerp, Belgium - Faculty of Medicine and Pharmaceutical Sciences, Free University of Brussels, Belgium
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    10.10.2011
Published in:
  • Plos one. - 2011, vol. 6, no. 10, p. e25488
English Several new human monoclonal antibodies (mAbs) with a neutralizing potential across different subtypes have recently been described. Three mAbs, HJ16, HGN194 and HK20, were obtained from patients within the HIV-1 cohort of the Institute of Tropical Medicine (ITM). Our aim was to generate immunization antibodies equivalent to those seen in plasma. Here, we describe the selection and characterization of patient plasma and their mAbs, using a range of neutralization assays, including several peripheral blood mononuclear cell (PBMC) based assays and replicating primary viruses as well as cell line based assays and pseudoviruses (PV). The principal criterion for selection of patient plasma was the activity in an ‘extended incubation phase’ PBMC assay. Neutralizing Abs, derived from their memory B cells, were then selected by ELISA with envelope proteins as solid phase. MAbs were subsequently tested in a high-throughput HOS-PV assay to assess functional neutralization. The present study indicates that the strong profiles in the patients' plasma were not solely due to antibodies represented by the newly isolated mAbs. Although results from the various assays were divergent, they by and large indicate that neutralizing Abs to other epitopes of the HIV-1 envelope are present in the plasma and synergy between Abs may be important. Thus, the spectrum of the obtained mAbs does not cover the range of cross-reactivity seen in plasma in these carefully selected patients irrespective of which neutralization assay is used. Nevertheless, these mAbs are relevant for immunogen discovery because they bind to the recombinant glycoproteins to which the immune response needs to be targeted in vivo. Our observations illustrate the remaining challenges required for successful immunogen design and development.
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  • English
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Medicine
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https://susi.usi.ch/usi/documents/318962
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