Journal article

Structure and function analysis of an antibody recognizing all influenza A subtypes

  • Kallewaard, Nicole L. Department of Infectious Disease and Vaccines, MedImmune LLC, One MedImmune Way, Gaithersburg, USA
  • Corti, Davide Humabs BioMed SA, Bellinzona, Switzerland
  • Collins, Patrick J. Mill Hill Laboratory, The Francis Crick Institute, London, UK
  • Neu, Ursula Mill Hill Laboratory, The Francis Crick Institute, London, UK
  • McAuliffe, Josephine M. Department of Infectious Disease and Vaccines, MedImmune LLC, One MedImmune Way, Gaithersburg, USA
  • Benjamin, Ebony Department of Infectious Disease and Vaccines, MedImmune LLC, One MedImmune Way, Gaithersburg, USA
  • Wachter-Rosati, Leslie Department of Infectious Disease and Vaccines, MedImmune LLC, One MedImmune Way, Gaithersburg, USA
  • Palmer-Hill, Frances J. Department of Infectious Disease and Vaccines, MedImmune LLC, One MedImmune Way, Gaithersburg, USA
  • Yuan, Andy Q. Department of Antibody Discovery and Protein Engineering, MedImmune LLC, One MedImmune Way, Gaithersburg, USA
  • Walker, Philip A. Structural Biology Science Technology Platform, Mill Hill Laboratory, Francis Crick Institute, London, UK
  • Vorlaender, Matthias K. Mill Hill Laboratory, The Francis Crick Institute, London, UK
  • Bianchi, Siro Humabs BioMed SA, Bellinzona, Switzerland
  • Guarino, Barbara Humabs BioMed SA, Bellinzona, Switzerland
  • De Marco, Anna Humabs BioMed SA, Bellinzona, Switzerland
  • Vanzetta, Fabrizia Humabs BioMed SA, Bellinzona, Switzerland
  • Agatic, Gloria Humabs BioMed SA, Bellinzona, Switzerland
  • Foglierini, Mathilde 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
  • Fernandez-Rodriguez, Blanca Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Fruehwirth, Alexander 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
  • Ogrodowicz, Roksana W. Structural Biology Science Technology Platform, Mill Hill Laboratory, Francis Crick Institute, London, UK
  • Martin, Stephen R. Structural Biology Science Technology Platform, Mill Hill Laboratory, Francis Crick Institute, London, UK
  • Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Suzich, JoAnn A. Department of Infectious Disease and Vaccines, MedImmune LLC, One MedImmune Way, Gaithersburg, USA
  • Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute for Microbiology, ETH Zurich, Switzerland
  • Zhu, Qing Department of Infectious Disease and Vaccines, MedImmune LLC, One MedImmune Way, Gaithersburg, USA
  • Gamblin, Steven J. Mill Hill Laboratory, The Francis Crick Institute, London, UK
  • Skehel, John J. Mill Hill Laboratory, The Francis Crick Institute, London, UK
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    21.07.2016
Published in:
  • Cell. - 2016, vol. 166, no. 3, p. 596-608
English Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross- reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans.
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  • English
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Medicine
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https://susi.usi.ch/usi/documents/319400
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