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

被引：33

作者：

Shiakolas, Andrea R. ^{[1
,2
]}

Kramer, Kevin J. ^{[1
,2
]}

Johnson, Nicole, V ^{[3
]}

Wall, Steven C. ^{[1
,2
]}

Suryadevara, Naveenchandra ^{[1
]}

Wrapp, Daniel ^{[3
]}

Periasamy, Sivakumar ^{[4
,5
]}

Pilewski, Kelsey A. ^{[1
,2
]}

Raju, Nagarajan ^{[1
,2
]}

Nargi, Rachel ^{[1
]}

Sutton, Rachel E. ^{[1
]}

Walker, Lauren M. ^{[1
,2
]}

Setliff, Ian ^{[1
]}

Crowe, James E. ^{[1
,2
,6
]}

Bukreyev, Alexander ^{[4
,5
,7
]}

Carnahan, Robert H. ^{[1
,6
]}

McLellan, Jason S. ^{[3
]}

Georgiev, Ivelin S. ^{[1
,2
,8
,9
,10
,11
]}

机构：

[1] Vanderbilt Univ, Vanderbilt Vaccine Ctr, Med Ctr, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA

[3] Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA

[4] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA

[5] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA

[6] Vanderbilt Univ, Dept Pediat, Med Ctr, Nashville, TN USA

[7] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA

[8] Vanderbilt Univ, Med Ctr, Vanderbilt Inst Infect Immunol & Inflammat, Nashville, TN 37232 USA

[9] Vanderbilt Univ, Dept Comp Sci, Nashville, TN 37232 USA

[10] Vanderbilt Univ, Ctr Struct Biol, Nashville, TN 37232 USA

[11] Vanderbilt Univ, Program Computat Microbiol & Immunol, Med Ctr, Nashville, TN 37232 USA

来源：

NATURE BIOTECHNOLOGY | 2022年 / 40卷 / 08期

关键词：

All Open Access; Bronze;

D O I：

10.1038/s41587-022-01232-2

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

B cell receptor sequencing with ligand blocking speeds up neutralizing antibody discovery. 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.

引用

页码：1270 / +

页数：16

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