IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms12780.html
   My bibliography  Save this article

A broadly neutralizing anti-influenza antibody reveals ongoing capacity of haemagglutinin-specific memory B cells to evolve

Author

Listed:
  • Ying Fu

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Zhen Zhang

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Jared Sheehan

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Yuval Avnir

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Callie Ridenour

    (Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases)

  • Thomas Sachnik

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Jiusong Sun

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • M. Jaber Hossain

    (Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases)

  • Li-Mei Chen

    (Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases)

  • Quan Zhu

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Ruben O. Donis

    (Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases)

  • Wayne A. Marasco

    (Dana-Farber Cancer Institute, Harvard Medical School)

Abstract

Understanding the natural evolution and structural changes involved in broadly neutralizing antibody (bnAb) development holds great promise for improving the design of prophylactic influenza vaccines. Here we report an haemagglutinin (HA) stem-directed bnAb, 3I14, isolated from human memory B cells, that utilizes a heavy chain encoded by the IGHV3-30 germline gene. MAb 3I14 binds and neutralizes groups 1 and 2 influenza A viruses and protects mice from lethal challenge. Analysis of VH and VL germline back-mutants reveals binding to H3 and H1 but not H5, which supports the critical role of somatic hypermutation in broadening the bnAb response. Moreover, a single VLD94N mutation improves the affinity of 3I14 to H5 by nearly 10-fold. These data provide evidence that memory B cell evolution can expand the HA subtype specificity. Our results further suggest that establishing an optimized memory B cell pool should be an aim of ‘universal’ influenza vaccine strategies.

Suggested Citation

  • Ying Fu & Zhen Zhang & Jared Sheehan & Yuval Avnir & Callie Ridenour & Thomas Sachnik & Jiusong Sun & M. Jaber Hossain & Li-Mei Chen & Quan Zhu & Ruben O. Donis & Wayne A. Marasco, 2016. "A broadly neutralizing anti-influenza antibody reveals ongoing capacity of haemagglutinin-specific memory B cells to evolve," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12780
    DOI: 10.1038/ncomms12780
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms12780
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/ncomms12780?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Xiaoyu Sun & Caixuan Liu & Xiao Lu & Zhiyang Ling & Chunyan Yi & Zhen Zhang & Zi Li & Mingliang Jin & Wenshuai Wang & Shubing Tang & Fangfang Wang & Fang Wang & Sonam Wangmo & Shuangfeng Chen & Li Li , 2022. "Unique binding pattern for a lineage of human antibodies with broad reactivity against influenza A virus," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12780. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.