IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-61472-z.html
   My bibliography  Save this article

Optimizing a human monoclonal antibody for better neutralization of SARS-CoV-2

Author

Listed:
  • Qian Wang

    (Columbia University Vagelos College of Physicians and Surgeons
    Columbia University Vagelos College of Physicians and Surgeons
    Columbia University Vagelos College of Physicians and Surgeons)

  • Yicheng Guo

    (Columbia University Vagelos College of Physicians and Surgeons
    Columbia University Vagelos College of Physicians and Surgeons)

  • Ryan G. Casner

    (Columbia University
    Columbia University Vagelos College of Physicians and Surgeons
    Sanofi R&D)

  • Jian Yu

    (Columbia University Vagelos College of Physicians and Surgeons)

  • Manoj S. Nair

    (Columbia University Vagelos College of Physicians and Surgeons)

  • Jerren Ho

    (Columbia University Vagelos College of Physicians and Surgeons)

  • Eswar R. Reddem

    (Columbia University
    Columbia University Vagelos College of Physicians and Surgeons)

  • Ian A. Mellis

    (Columbia University Vagelos College of Physicians and Surgeons)

  • Madeline Wu

    (Columbia University Vagelos College of Physicians and Surgeons)

  • Chih-Chen Tzang

    (Columbia University Vagelos College of Physicians and Surgeons)

  • Hsiang Hong

    (Columbia University Vagelos College of Physicians and Surgeons)

  • Yaoxing Huang

    (Columbia University Vagelos College of Physicians and Surgeons
    Columbia University Vagelos College of Physicians and Surgeons
    Columbia University Vagelos College of Physicians and Surgeons)

  • Lawrence Shapiro

    (Columbia University Vagelos College of Physicians and Surgeons
    Columbia University
    Columbia University Vagelos College of Physicians and Surgeons)

  • Lihong Liu

    (Columbia University Vagelos College of Physicians and Surgeons
    Columbia University Vagelos College of Physicians and Surgeons
    Wuhan University)

  • David D. Ho

    (Columbia University Vagelos College of Physicians and Surgeons
    Columbia University Vagelos College of Physicians and Surgeons
    Columbia University Vagelos College of Physicians and Surgeons
    Columbia University Vagelos College of Physicians and Surgeons)

Abstract

SARS-CoV-2 has largely evolved to resist antibody pressure, with each successive viral variant becoming more and more resistant to serum antibodies in the population. This evolution renders all previously authorized anti-spike therapeutic monoclonal antibodies inactive, and it threatens the remaining pipelines against COVID-19. We report herein the isolation of a human monoclonal antibody with a broad but incomplete SARS-CoV-2 neutralization profile, but structural analyses and mutational scanning lead to the engineering of variants that result in greater antibody flexibility while binding to the viral spike. Three such optimized monoclonal antibodies neutralize all SARS-CoV-2 strains tested with much improved potency and breadth, including against subvariants XEC and LP.8.1. The findings of this study not only present antibody candidates for clinical development against COVID-19, but also introduce an engineering approach to improve antibody activity via increasing conformational flexibility.

Suggested Citation

  • Qian Wang & Yicheng Guo & Ryan G. Casner & Jian Yu & Manoj S. Nair & Jerren Ho & Eswar R. Reddem & Ian A. Mellis & Madeline Wu & Chih-Chen Tzang & Hsiang Hong & Yaoxing Huang & Lawrence Shapiro & Liho, 2025. "Optimizing a human monoclonal antibody for better neutralization of SARS-CoV-2," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61472-z
    DOI: 10.1038/s41467-025-61472-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-61472-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-61472-z?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
    ---><---

    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:16:y:2025:i:1:d:10.1038_s41467-025-61472-z. 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.