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

tetano

Editor, Senior Moderator
Nat Biotechnol


. 2022 Mar 3.
doi: 10.1038/s41587-022-01232-2. Online ahead of print.
Efficient discovery of SARS-CoV-2-neutralizing antibodies via B cell receptor sequencing and ligand blocking


Andrea R Shiakolas[SUP] 1 2 [/SUP], Kevin J Kramer[SUP] #[/SUP][SUP] 1 2 [/SUP], Nicole V Johnson[SUP] #[/SUP][SUP] 3 [/SUP], Steven C Wall[SUP] #[/SUP][SUP] 1 2 [/SUP], Naveenchandra Suryadevara[SUP] 1 [/SUP], Daniel Wrapp[SUP] 3 [/SUP], Sivakumar Periasamy[SUP] 4 5 [/SUP], Kelsey A Pilewski[SUP] 1 2 [/SUP], Nagarajan Raju[SUP] 1 2 [/SUP], Rachel Nargi[SUP] 1 [/SUP], Rachel E Sutton[SUP] 1 [/SUP], Lauren M Walker[SUP] 1 2 [/SUP], Ian Setliff[SUP] 1 [/SUP], James E Crowe Jr[SUP] 1 2 6 [/SUP], Alexander Bukreyev[SUP] 4 5 7 [/SUP], Robert H Carnahan[SUP] 1 6 [/SUP], Jason S McLellan[SUP] 3 [/SUP], Ivelin S Georgiev[SUP] 8 9 10 11 12 13 [/SUP]



Affiliations

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.
 
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