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IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern

Author

Listed:
  • Matthew R. Chang

    (Dana-Farber Cancer Institute)

  • Luke Tomasovic

    (Dana-Farber Cancer Institute)

  • Natalia A. Kuzmina

    (University of Texas Medical Branch
    Galveston National Laboratory
    University of Texas Medical Branch)

  • Adam J. Ronk

    (University of Texas Medical Branch
    Galveston National Laboratory
    University of Texas Medical Branch)

  • Patrick O. Byrne

    (University of Texas)

  • Rebecca Johnson

    (Boston University, School of Medicine)

  • Nadia Storm

    (Boston University, School of Medicine)

  • Eduardo Olmedillas

    (La Jolla Institute for Immunology)

  • Yixuan J. Hou

    (University of North Carolina at Chapel Hill)

  • Alexandra Schäfer

    (University of North Carolina at Chapel Hill)

  • Sarah R. Leist

    (University of North Carolina at Chapel Hill)

  • Longping V. Tse

    (University of North Carolina at Chapel Hill)

  • Hanzhong Ke

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Christian Coherd

    (Dana-Farber Cancer Institute)

  • Katrina Nguyen

    (Dana-Farber Cancer Institute)

  • Maliwan Kamkaew

    (Dana-Farber Cancer Institute)

  • Anna Honko

    (Boston University, School of Medicine)

  • Quan Zhu

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Galit Alter

    (MIT and Harvard)

  • Erica Ollmann Saphire

    (La Jolla Institute for Immunology)

  • Jason S. McLellan

    (University of Texas)

  • Anthony Griffiths

    (Boston University, School of Medicine)

  • Ralph S. Baric

    (University of North Carolina at Chapel Hill)

  • Alexander Bukreyev

    (University of Texas Medical Branch
    Galveston National Laboratory
    University of Texas Medical Branch)

  • Wayne A. Marasco

    (Dana-Farber Cancer Institute
    Harvard Medical School)

Abstract

Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being employed to mitigate these challenges, but neutralization escape remains a major challenge and alternative strategies are needed. Here we present two anti-SARS-CoV-2 spike binding antibodies, one Class 1 and one Class 4, selected from our non-immune human single-chain variable fragment (scFv) phage library, that are engineered into four, fully-human IgG-like bispecific antibodies (BsAb). Prophylaxis of hACE2 mice and post-infection treatment of golden hamsters demonstrates the efficacy of the monospecific antibodies against the original Wuhan strain, while promising in vitro results with the BsAbs demonstrate enhanced binding and distinct synergistic effects on neutralizing activity against circulating variants of concern. In particular, one BsAb engineered in a tandem scFv-Fc configuration shows synergistic neutralization activity against several variants of concern including B.1.617.2. This work provides evidence that synergistic neutralization can be achieved using a BsAb scaffold, and serves as a foundation for the future development of broadly reactive BsAbs against emerging variants of concern.

Suggested Citation

  • Matthew R. Chang & Luke Tomasovic & Natalia A. Kuzmina & Adam J. Ronk & Patrick O. Byrne & Rebecca Johnson & Nadia Storm & Eduardo Olmedillas & Yixuan J. Hou & Alexandra Schäfer & Sarah R. Leist & Lon, 2022. "IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33030-4
    DOI: 10.1038/s41467-022-33030-4
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    References listed on IDEAS

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