Efficient discovery of SARS-CoV-2-neutralizing antibodies via B cell receptor sequencing and ligand blocking

Andrea R. Shiakolas, Kevin J. Kramer, Nicole V. Johnson, Steven C. Wall, Naveenchandra Suryadevara, Daniel Wrapp, Sivakumar Periasamy, Kelsey A. Pilewski, Nagarajan Raju, Rachel Nargi, Rachel E. Sutton, Lauren M. Walker, Ian Setliff, James E. Crowe, Alexander Bukreyev, Robert H. Carnahan, Jason S. McLellan, Ivelin S. Georgiev

    Research output: Contribution to journalArticlepeer-review

    10 Scopus citations

    Abstract

    Although several monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been approved for coronavirus disease 2019 (COVID-19) therapy, development was generally inefficient, with lead generation often requiring the production and testing of numerous antibody candidates. Here, we report that the integration of target–ligand blocking with a previously described B cell receptor-sequencing approach (linking B cell receptor to antigen specificity through sequencing (LIBRA-seq)) enables the rapid and efficient identification of multiple neutralizing mAbs that prevent the binding of SARS-CoV-2 spike (S) protein to angiotensin-converting enzyme 2 (ACE2). The combination of target–ligand blocking and high-throughput antibody sequencing promises to increase the throughput of programs aimed at discovering new neutralizing antibodies.

    Original languageEnglish (US)
    Pages (from-to)1270-1275
    Number of pages6
    JournalNature Biotechnology
    Volume40
    Issue number8
    DOIs
    StatePublished - Aug 2022

    ASJC Scopus subject areas

    • Biotechnology
    • Bioengineering
    • Biomedical Engineering
    • Applied Microbiology and Biotechnology
    • Molecular Medicine

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