Rapid discovery of diverse neutralizing SARS-CoV-2 antibodies from large-scale synthetic phage libraries

被引：18

作者：

Yuan, Tom Z. ^{[1
]}

Garg, Pankaj ^{[2
]}

Wang, Linya ^{[1
]}

Willis, Jordan R. ^{[3
]}

Kwan, Eric ^{[1
]}

Hernandez, Ana G. Lujan ^{[1
]}

Tuscano, Emily ^{[1
]}

Sever, Emily N. ^{[1
]}

Keane, Erica ^{[4
]}

Soto, Cinque ^{[5
]}

Mucker, Eric M. ^{[6
]}

Fouch, Mallorie E. ^{[7
]}

Davidson, Edgar ^{[7
]}

Doranz, Benjamin J. ^{[7
]}

Kailasan, Shweta ^{[8
]}

Aman, M. Javad ^{[8
]}

Li, Haoyang ^{[9
]}

Hooper, Jay W. ^{[6
]}

Saphire, Erica Ollmann ^{[9
,10
]}

Crowe, James E. ^{[5
,11
,12
]}

Liu, Qiang ^{[1
]}

Axelrod, Fumiko ^{[1
]}

Sato, Aaron K. ^{[1
]}

机构：

[1] Twist Biosci, Twist Biopharma, 681 Gateway Blvd, San Francisco, CA 94080 USA

[2] Alamar Biosci, Fremont, CA USA

[3] Scripps Res, IAVI Neutralizing Antibody Ctr, La Jolla, CA USA

[4] Univ Calif Santa Barbara, Neurosci Res Inst, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA

[5] Vanderbilt Univ, Med Ctr, Vanderbilt Vaccine Ctr, Nashville, TN USA

[6] US Army, Med Res Inst Infect Dis, Frederick, MD USA

[7] Integral Mol, Philadelphia, PA USA

[8] Integrated BioTherapeut Inc, Rockville, MD USA

[9] La Jolla Inst Immunol, Ctr Infect Dis & Vaccine Res, La Jolla, CA USA

[10] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

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

[12] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA

来源：

MABS | 2022年 / 14卷 / 01期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

SARS-CoV-2; neutralizing antibody; COVID-19; spike glycoprotein; synthetic libraries; HUMAN MONOCLONAL-ANTIBODY; RECEPTOR-BINDING DOMAIN; SARS CORONAVIRUS; IDENTIFICATION; RECOGNITION; ENTRY;

D O I：

10.1080/19420862.2021.2002236

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Coronavirus disease 2019 (COVID-19) is an evolving global public health crisis in need of therapeutic options. Passive immunization of monoclonal antibodies (mAbs) represents a promising therapeutic strategy capable of conferring immediate protection from SARS-CoV-2 infection. Herein, we describe the discovery and characterization of neutralizing SARS-CoV-2 IgG and VHH antibodies from four large-scale phage libraries. Each library was constructed synthetically with shuffled complementarity-determining region loops from natural llama and human antibody repertoires. While most candidates targeted the receptor-binding domain of the S1 subunit of SARS-CoV-2 spike protein, we also identified a neutralizing IgG candidate that binds a unique epitope on the N-terminal domain. A select number of antibodies retained binding to SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa and Delta. Overall, our data show that synthetic phage libraries can rapidly yield SARS-CoV-2 S1 antibodies with therapeutically desirable features, including high affinity, unique binding sites, and potent neutralizing activity in vitro, and a capacity to limit disease in vivo.

引用

页数：17

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