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

mAbs

Pankaj Garg¹  Jordan R. Willis²  Benjamin J. Doranz³  Edgar Davidson³  Mallorie E. Fouch³  M. Javad Aman⁴  Shweta Kailasan⁴  Haoyang Li⁵  Erica Ollmann Saphire⁵  Erica Keane⁶  Emily N. Sever⁷  Linya Wang⁷  Eric Kwan⁷  Tom Z. Yuan⁷  Emily Tuscano⁷  Fumiko Axelrod⁷  Qiang Liu⁷  Ana G Lujan Hernandez⁷  Aaron K. Sato⁷  Eric M. Mucker⁸  Jay W. Hooper⁸  James E. Crowe⁹  Cinque Soto⁹ 

[1] Alamar Biosciences;IAVI Neutralizing Antibody Center, Scripps Research;Integral Molecular;Integrated BioTherapeutics, Inc. Rockville;La Jolla Institute for Immunology;Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California;Twist Bioscience;United States Army Medical Research Institute of Infectious Diseases;Vanderbilt Vaccine Center, Vanderbilt University Medical Center;

关键词: sars-cov-2;    neutralizing antibody;    covid-19;    spike glycoprotein;    synthetic libraries;   

DOI  :  10.1080/19420862.2021.2002236

来源: DOAJ

【 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.

【 授权许可】

Unknown