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Identification and Structure of a Multidonor Class of Head-Directed Influenza-Neutralizing Antibodies Reveal the Mechanism for Its Recurrent Elicitation

  1. Author:
    Cheung, Crystal Sao-Fong
    Fruehwirth, Alexander
    Paparoditis, Philipp Carl Georg
    Shen, Chen-Hsiang
    Foglierini, Mathilde
    Joyce, M Gordon
    Leung, Kwanyee
    Piccoli, Luca
    Rawi, Reda
    Silacci-Fregni, Chiara
    Tsybovsky,Yaroslav
    Verardi, Raffaello
    Wang, Lingshu
    Wang, Shuishu
    Yang, Eun Sung
    Zhang, Baoshan
    Zhang, Yi
    Chuang, Gwo-Yu
    Corti, Davide
    Mascola, John R
    Shapiro, Lawrence
    Kwong, Peter D
    Lanzavecchia, Antonio
    Zhou, Tongqing

  2. Author Address

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Institute for Research in Biomedicine, Universit 224; della Svizzera italiana, 6500 Bellinzona, Switzerland., Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA., Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. Electronic address: pdkwong@nih.gov., Institute for Research in Biomedicine, Universit 224; della Svizzera italiana, 6500 Bellinzona, Switzerland. Electronic address: lanzavecchia@irb.usi.ch., Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: tzhou@nih.gov.,
    1. Year: 2020
    2. Date: Sep 01
  2. Journal: Cell reports
    1. 32
    2. 9
    3. Pages: 108088
  4. Type of Article: Article
  5. Article Number: 108088
  6. ISSN: 2211-1247
  1. Abstract:

    Multidonor antibodies are of interest for vaccine design because they can in principle be elicited in the general population by a common set of immunogens. For influenza, multidonor antibodies have been observed against the hemagglutinin (HA) stem, but not the immunodominant HA head. Here, we identify and characterize a multidonor antibody class (LPAF-a class) targeting the HA head. This class exhibits potent viral entry inhibition against H1N1 A/California/04/2009 (CA09) virus. LPAF-a class antibodies derive from the HV2-70 gene and contain a "Tyr-Gly-Asp"-motif, which occludes the HA-sialic acid binding site as revealed by a co-crystal structure with HA. Both germline-reverted and mature LPAF antibodies potently neutralize CA09 virus and have nanomolar affinities for CA09 HA. Moreover, increased frequencies for LPFA-a class antibodies are observed in humans after a single vaccination. Overall, this work highlights the identification of a multidonor class of head-directed influenza-neutralizing antibodies and delineates the mechanism of their recurrent elicitation in humans. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2020.108088
  3. PMID: 32877670
  4. View record in Web of Science®
  5. WOS: 000565154100006
  6. PII : S2211-1247(20)31077-9

Library Notes

  1. Fiscal Year: FY2020-2021
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