IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-23825-2.html
   My bibliography  Save this article

Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers

Author

Listed:
  • Edurne Rujas

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute
    University of Toronto
    University of the Basque Country (UPV/EHU))

  • Iga Kucharska

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute)

  • Yong Zi Tan

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute)

  • Samir Benlekbir

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute)

  • Hong Cui

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute)

  • Tiantian Zhao

    (University of Toronto)

  • Gregory A. Wasney

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute
    The Hospital for Sick Children Research Institute)

  • Patrick Budylowski

    (University of Toronto
    Institute of Medical Science, University of Toronto)

  • Furkan Guvenc

    (University of Toronto
    University of Toronto)

  • Jocelyn C. Newton

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute)

  • Taylor Sicard

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute
    University of Toronto)

  • Anthony Semesi

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute)

  • Krithika Muthuraman

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute)

  • Amy Nouanesengsy

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute
    University of Toronto)

  • Clare Burn Aschner

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute)

  • Katherine Prieto

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute)

  • Stephanie A. Bueler

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute)

  • Sawsan Youssef

    (Distributed Bio)

  • Sindy Liao-Chan

    (Distributed Bio)

  • Jacob Glanville

    (Distributed Bio)

  • Natasha Christie-Holmes

    (University of Toronto)

  • Samira Mubareka

    (University of Toronto
    Sunnybrook Health Sciences Centre)

  • Scott D. Gray-Owen

    (University of Toronto)

  • John L. Rubinstein

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute
    University of Toronto
    University of Toronto)

  • Bebhinn Treanor

    (University of Toronto
    University of Toronto
    University of Toronto Scarborough)

  • Jean-Philippe Julien

    (Program in Molecular Medicine, The Hospital for Sick Children Research Institute
    University of Toronto
    University of Toronto)

Abstract

SARS-CoV-2, the virus responsible for COVID-19, has caused a global pandemic. Antibodies can be powerful biotherapeutics to fight viral infections. Here, we use the human apoferritin protomer as a modular subunit to drive oligomerization of antibody fragments and transform antibodies targeting SARS-CoV-2 into exceptionally potent neutralizers. Using this platform, half-maximal inhibitory concentration (IC50) values as low as 9 × 10−14 M are achieved as a result of up to 10,000-fold potency enhancements compared to corresponding IgGs. Combination of three different antibody specificities and the fragment crystallizable (Fc) domain on a single multivalent molecule conferred the ability to overcome viral sequence variability together with outstanding potency and IgG-like bioavailability. The MULTi-specific, multi-Affinity antiBODY (Multabody or MB) platform thus uniquely leverages binding avidity together with multi-specificity to deliver ultrapotent and broad neutralizers against SARS-CoV-2. The modularity of the platform also makes it relevant for rapid evaluation against other infectious diseases of global health importance. Neutralizing antibodies are a promising therapeutic for SARS-CoV-2.

Suggested Citation

  • Edurne Rujas & Iga Kucharska & Yong Zi Tan & Samir Benlekbir & Hong Cui & Tiantian Zhao & Gregory A. Wasney & Patrick Budylowski & Furkan Guvenc & Jocelyn C. Newton & Taylor Sicard & Anthony Semesi & , 2021. "Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23825-2
    DOI: 10.1038/s41467-021-23825-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-23825-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-23825-2?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:12:y:2021:i:1:d:10.1038_s41467-021-23825-2. 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.