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[Preprint]. 2021 Jun 30:2021.06.02.446813. Originally published 2021 Jun 2. [Version 2] doi: 10.1101/2021.06.02.446813

Efficient discovery of potently neutralizing SARS-CoV-2 antibodies using LIBRA-seq with ligand blocking

Andrea R Shiakolas, Nicole Johnson, Kevin J Kramer, Naveenchandra Suryadevara, Daniel Wrapp, Sivakumar Periasamy, Kelsey A Pilewski, Nagarajan Raju, Rachel Nargi, Rachel E Sutton, Lauren Walker, Ian Setliff, James E Crowe, Alexander Bukreyev, Robert H Carnahan, Jason S McLellan, Ivelin S Georgiev
PMCID: PMC8183015  PMID: 34100018

ABSTRACT

SARS-CoV-2 therapeutic antibody discovery efforts have met with notable success but have been associated with a generally inefficient process, requiring the production and characterization of exceptionally large numbers of candidates for the identification of a small set of leads. Here, we show that incorporating antibody–ligand blocking as part of LIBRA-seq, the high-throughput sequencing platform for antibody discovery, results in efficient identification of ultra-potent neutralizing antibodies against SARS-CoV-2. LIBRA-seq with ligand blocking is a general platform for functional antibody discovery targeting the disruption of antigen–ligand interactions.

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