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

[tetano]

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



Affiliations

• PMID: 35241839
• DOI: 10.1038/s41587-022-01232-2

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.