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

17 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

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

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