21
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Vaccine-induced HIV-1 envelope gp120 constant region 1-specific antibodies expose a CD4-inducible epitope and block the interaction of HIV-1 gp140 with galactosylceramide.

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Mucosal epithelial cell surface galactosylceramide (Galcer) has been postulated to be a receptor for HIV-1 envelope (Env) interactions with mucosal epithelial cells. Disruption of the HIV-1 Env interaction with such alternate receptors could be one strategy to prevent HIV-1 entry through the mucosal barrier. To study antibody modulation of HIV-1 Env-Galcer interactions, we used Galcer-containing liposomes to assess whether natural- and vaccine-induced monoclonal antibodies can block HIV-1 Env binding to Galcer. HIV-1 Env gp140 proteins bound to Galcer liposomes with Kds (dissociation constants) in the nanomolar range. Several HIV-1 ALVAC/AIDSVAX vaccinee-derived monoclonal antibodies (MAbs) specific for the gp120 first constant (C1) region blocked Galcer binding of a transmitted/founder HIV-1 Env gp140. Among the C1-specific MAbs that showed Galcer blocking, the antibody-dependent cellular cytotoxicity-mediating CH38 IgG and its natural IgA isotype were the most potent blocking antibodies. C1-specific IgG monoclonal antibodies that blocked Env binding to Galcer induced upregulation of the gp120 CD4-inducible (CD4i) epitope bound by MAb 17B, demonstrating that a conformational change in gp120 may be required for Galcer blocking. However, the MAb 17B itself did not block Env-Galcer binding, suggesting that the C1 antibody-induced gp120 conformational changes resulted in alteration in a Galcer binding site distant from the CD4i 17B MAb binding site.

          Related collections

          Author and article information

          Journal
          J. Virol.
          Journal of virology
          American Society for Microbiology
          1098-5514
          0022-538X
          Aug 2014
          : 88
          : 16
          Affiliations
          [1 ] Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
          [2 ] Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
          [3 ] Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA Department of Immunology, Duke University School of Medicine, Durham, North Carolina, USA Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.
          [4 ] Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
          [5 ] Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA Department of Immunology, Duke University School of Medicine, Durham, North Carolina, USA Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.
          [6 ] Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
          [7 ] U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
          [8 ] Tropical Hygiene, Mahidol University, Bangkok, Thailand.
          [9 ] Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
          [10 ] Clinical Tropical Medicine, Mahidol University, Bangkok, Thailand.
          [11 ] Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand.
          [12 ] Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA Department of Immunology, Duke University School of Medicine, Durham, North Carolina, USA alam0004@mc.duke.edu hayne002@mc.duke.edu.
          [13 ] Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA Department of Pathology, Duke University School of Medicine, Durham, North Carolina, USA alam0004@mc.duke.edu hayne002@mc.duke.edu.
          Article
          JVI.01031-14
          10.1128/JVI.01031-14
          4136246
          24920809
          c016c9d5-726c-4795-9bef-5c99d886255c

          Comments

          Comment on this article