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

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...

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Veröffentlicht in:Nature biotechnology 2022-08, Vol.40 (8), p.1270-1275
Hauptverfasser: Shiakolas, Andrea R., Kramer, Kevin J., Johnson, Nicole V., Wall, Steven C., Suryadevara, Naveenchandra, Wrapp, Daniel, Periasamy, Sivakumar, Pilewski, Kelsey A., Raju, Nagarajan, Nargi, Rachel, Sutton, Rachel E., Walker, Lauren M., Setliff, Ian, Crowe, James E., Bukreyev, Alexander, Carnahan, Robert H., McLellan, Jason S., Georgiev, Ivelin S.
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container_end_page 1275
container_issue 8
container_start_page 1270
container_title Nature biotechnology
container_volume 40
creator Shiakolas, Andrea R.
Kramer, Kevin J.
Johnson, Nicole V.
Wall, Steven C.
Suryadevara, Naveenchandra
Wrapp, Daniel
Periasamy, Sivakumar
Pilewski, Kelsey A.
Raju, Nagarajan
Nargi, Rachel
Sutton, Rachel E.
Walker, Lauren M.
Setliff, Ian
Crowe, James E.
Bukreyev, Alexander
Carnahan, Robert H.
McLellan, Jason S.
Georgiev, Ivelin S.
description 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. B cell receptor sequencing with ligand blocking speeds up neutralizing antibody discovery.
doi_str_mv 10.1038/s41587-022-01232-2
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subjects 631/1647/2163
631/1647/514/2254
631/250/2152/2153
631/250/255
ACE2
Agriculture
Angiotensin
Angiotensin-converting enzyme 2
Antibodies
Antigens
Bioinformatics
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Coronaviruses
COVID-19
COVID-19 vaccines
Experiments
Immunology
Influenza
Life Sciences
Ligands
Medical research
Monoclonal antibodies
Neutralizing
Pandemics
Peptidyl-dipeptidase A
Proteins
Receptors
Severe acute respiratory syndrome coronavirus 2
Viral diseases
title Efficient discovery of SARS-CoV-2-neutralizing antibodies via B cell receptor sequencing and ligand blocking
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