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

Andrea R ShiakolasKevin J KramerNicole V JohnsonSteven C WallNaveen Chandra SuryadevaraDaniel WrappSivakumar PeriasamyKelsey A PilewskiNagarajan RajuRachel NargiRachel E SuttonLauren M WalkerIan SetliffJames E CroweAlexander BukreyevRobert H CarnahanJason S MclellanIvelin S Georgiev
Published in: Nature biotechnology (2022)
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.
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