@article{af4af42893d94b0a852ea7ec9264a4d1,
title = "Efficient discovery of SARS-CoV-2-neutralizing antibodies via B cell receptor sequencing and ligand blocking",
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.",
author = "Shiakolas, {Andrea R.} and Kramer, {Kevin J.} and Johnson, {Nicole V.} and Wall, {Steven C.} and Naveenchandra Suryadevara and Daniel Wrapp and Sivakumar Periasamy and Pilewski, {Kelsey A.} and Nagarajan Raju and Rachel Nargi and Sutton, {Rachel E.} and Walker, {Lauren M.} and Ian Setliff and Crowe, {James E.} and Alexander Bukreyev and Carnahan, {Robert H.} and McLellan, {Jason S.} and Georgiev, {Ivelin S.}",
note = "Funding Information: We thank A. Jones, L. Raju and J. Roberson of VANTAGE for their expertise regarding next-generation sequencing and library preparation, D. Flaherty and B. Matlock of the Vanderbilt Flow Cytometry Shared Resource for help with flow panel optimization and members of the Georgiev laboratory for comments on the manuscript. The Vanderbilt VANTAGE Core provided technical assistance for this work. VANTAGE is supported, in part, by CTSA grant 5UL1 RR024975-03, the Vanderbilt Ingram Cancer Center (P30 CA68485), the Vanderbilt Vision Center (P30 EY08126) and NIH/NCRR (G20 RR030956). This work was conducted, in part, using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University. Flow cytometry experiments were performed in the Vanderbilt University Medical Center (VUMC) Flow Cytometry Shared Resource. The VUMC Flow Cytometry Shared Resource is supported by the Vanderbilt Ingram Cancer Center (P30 CA68485) and the Vanderbilt Digestive Disease Research Center (DK058404). For work described in this manuscript, I.S.G., A.R.S., K.J.K., S.C.W., K.A.P., N.R. and L.M.W. were supported, in part, by NIH National Institute of Allergy and Infectious Diseases (NIAID) award R01AI131722-S1, the Hays Foundation COVID-19 Research Fund, Fast Grants and CTSA award number UL1 TR002243 from the National Center for Advancing Translational Sciences. J.S.M, N.V.J. and D.W. were supported, in part, by an NIH NIAID grant awarded to J.S.M. (R01-AI127521), a Welch Foundation grant F-0003-19620604 and an NIH NIAID award R01AI131722-S1. S.P. and A.B. were supported, in part, by the NIAID grants U19AI142785 and U19 AI142790. J.E.C., N.S., R.N., R.E.S. and R.H.C. were supported, in part, by Defense Advanced Research Projects Agency (DARPA) grant HR0011-18-2-0001, US NIH contract 75N93019C00074, NIH grant R01 AI157155, the Dolly Parton COVID-19 Research Fund at Vanderbilt and a grant from Fast Grants, Mercatus Center, George Mason University. J.E.C. is a recipient of the 2019 Future Insight Prize from Merck KGaA, which supported this work with a grant. Funding Information: We thank A. Jones, L. Raju and J. Roberson of VANTAGE for their expertise regarding next-generation sequencing and library preparation, D. Flaherty and B. Matlock of the Vanderbilt Flow Cytometry Shared Resource for help with flow panel optimization and members of the Georgiev laboratory for comments on the manuscript. The Vanderbilt VANTAGE Core provided technical assistance for this work. VANTAGE is supported, in part, by CTSA grant 5UL1 RR024975-03, the Vanderbilt Ingram Cancer Center (P30 CA68485), the Vanderbilt Vision Center (P30 EY08126) and NIH/NCRR (G20 RR030956). This work was conducted, in part, using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University. Flow cytometry experiments were performed in the Vanderbilt University Medical Center (VUMC) Flow Cytometry Shared Resource. The VUMC Flow Cytometry Shared Resource is supported by the Vanderbilt Ingram Cancer Center (P30 CA68485) and the Vanderbilt Digestive Disease Research Center (DK058404). For work described in this manuscript, I.S.G., A.R.S., K.J.K., S.C.W., K.A.P., N.R. and L.M.W. were supported, in part, by NIH National Institute of Allergy and Infectious Diseases (NIAID) award R01AI131722-S1, the Hays Foundation COVID-19 Research Fund, Fast Grants and CTSA award number UL1 TR002243 from the National Center for Advancing Translational Sciences. J.S.M, N.V.J. and D.W. were supported, in part, by an NIH NIAID grant awarded to J.S.M. (R01-AI127521), a Welch Foundation grant F-0003-19620604 and an NIH NIAID award R01AI131722-S1. S.P. and A.B. were supported, in part, by the NIAID grants U19AI142785 and U19 AI142790. J.E.C., N.S., R.N., R.E.S. and R.H.C. were supported, in part, by Defense Advanced Research Projects Agency (DARPA) grant HR0011-18-2-0001, US NIH contract 75N93019C00074, NIH grant R01 AI157155, the Dolly Parton COVID-19 Research Fund at Vanderbilt and a grant from Fast Grants, Mercatus Center, George Mason University. J.E.C. is a recipient of the 2019 Future Insight Prize from Merck KGaA, which supported this work with a grant. Funding Information: A.R.S. and I.S.G. are cofounders of AbSeek Bio. I.S.G., A.R.S. and K.J.K. are listed as inventors on antibodies described herein. I.S.G., A.R.S. and I.S. are listed as inventors on patent applications for the LIBRA-seq technology. J.E.C. has served as a consultant for Luna Biologics, is a member of the Scientific Advisory Board Meissa Vaccines and is Founder of IDBiologics. The Crowe laboratory has received funding support in sponsored research agreements from AstraZeneca, IDBiologics and Takeda. The Georgiev laboratory at VUMC has received unrelated funding from Takeda Pharmaceuticals. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = aug,
doi = "10.1038/s41587-022-01232-2",
language = "English (US)",
volume = "40",
pages = "1270--1275",
journal = "Bio/Technology",
issn = "1087-0156",
publisher = "Nature Publishing Group",
number = "8",
}