Journal article

Structural basis for broad HIV-1 neutralization by the MPER-specific human broadly neutralizing antibody LN01

  • Pinto, Dora Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Fenwick, Craig Swiss Vaccine Research Institute, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland
  • Caillat, Christophe Institut de Biologie Structurale (IBS), University Grenoble Alpes, CEA, CNRS, 38000 Grenoble, France
  • Silacci, Chiara Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Guseva, Serafima Institut de Biologie Structurale (IBS), University Grenoble Alpes, CEA, CNRS, 38000 Grenoble, France
  • Dehez, François LPCT, UMR 7019 Université de Lorraine CNRS, 54500 Vandoeuvre-lès-Nancy, France - Laboratoire International Associé CNRS and University of Illinois at Urbana-Champaign, LPCT, UMR 7019 Université de Lorraine CNRS, Vandoeuvre-lès-Nancy 54500, France
  • Chipot, Christophe LPCT, UMR 7019 Université de Lorraine CNRS, 54500 Vandoeuvre-lès-Nancy, France - Laboratoire International Associé CNRS and University of Illinois at Urbana-Champaign, LPCT, UMR 7019 Université de Lorraine CNRS, Vandoeuvre-lès-Nancy 54500, France - Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
  • Barbieri, Sonia ,Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Minola, Andrea Humabs Biomed SA, Vir Biotechnology, 6500 Bellinzona, Ticino, Switzerland
  • Jarrossay, David ,Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Tomaras, Georgia D. Duke Human Vaccine Institute, Durham, NC 27710, USA - Paris Diderot University, Sorbonne Paris Cité, Paris 75013, France
  • Shen, Xiaoying Duke Human Vaccine Institute, Durham, NC 27710, USA
  • Riva, Agostino Department of Biomedical and Clinical Sciences, Luigi Sacco University Hospital, Università di Milano, 20157 Milan, Italy - III Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy
  • Tarkowski, Maciej Department of Biomedical and Clinical Sciences, Luigi Sacco University Hospital, Università di Milano, 20157 Milan, Italy
  • Schwartz, Olivier Institut Pasteur, Virus & Immunity Unit, CNRS UMR 3569, Paris 75015, France - Vaccine Research Institute, 94000 Créteil, France
  • Bruel, Timothée Institut Pasteur, Virus & Immunity Unit, CNRS UMR 3569, Paris 75015, France - Vaccine Research Institute, 94000 Créteil, France
  • Dufloo, Jérémy Institut Pasteur, Virus & Immunity Unit, CNRS UMR 3569, Paris 75015, France - Vaccine Research Institute, 94000 Créteil, France - Paris Diderot University, Sorbonne Paris Cité, Paris 75013, France
  • Seaman, Michael S. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
  • Montefiori, David C. Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
  • Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Corti, Davide Humabs Biomed SA, Vir Biotechnology, 6500 Bellinzona, Ticino, Switzerland
  • Pantaleo, Giuseppe Swiss Vaccine Research Institute, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland - Service of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland
  • Weissenhorn, Winfried Institut de Biologie Structurale (IBS), University Grenoble Alpes, CEA, CNRS, 38000 Grenoble, France
Show more…
    13.11.2019
Published in:
  • Cell host & microbe. - 2019, vol. 26, no. 5, p. p. 623-637.e8
English Potent and broadly neutralizing antibodies (bnAbs) are the hallmark of HIV-1 protection by vaccination. The membrane-proximal external region (MPER) of the HIV-1 gp41 fusion protein is targeted by the most broadly reactive HIV-1 neutralizing antibodies. Here, we examine the structural and molecular mechansims of neutralization by anti-MPER bnAb, LN01, which was isolated from lymph-node-derived germinal center B cells of an elite controller and exhibits broad neutralization breadth. LN01 engages both MPER and the transmembrane (TM) region, which together form a continuous helix in complex with LN01. The tilted TM orientation allows LN01 to interact simultaneously with the peptidic component of the MPER epitope and membrane via two specific lipid binding sites of the antibody paratope. Although LN01 carries a high load of somatic mutations, most key residues interacting with the MPER epitope and lipids are germline encoded, lending support for the LN01 epitope as a candidate for lineage-based vaccine development.
Language
  • English
Classification
Biology, life sciences
License
License undefined
Identifiers
Persistent URL
https://susi.usi.ch/usi/documents/319183
Statistics

Document views: 32 File downloads:
  • Pinto_chm_2019.pdf: 5