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

• Published in: mAbs Vol. 14; no. 1; p. 2002236
• Main Authors: Yuan, Tom Z, Garg, Pankaj, Wang, Linya, Willis, Jordan R, Kwan, Eric, Hernandez, Ana G Lujan, Tuscano, Emily, Sever, Emily N, Keane, Erica, Soto, Cinque, Mucker, Eric M, Fouch, Mallorie E, Davidson, Edgar, Doranz, Benjamin J, Kailasan, Shweta, Aman, M Javad, Li, Haoyang, Hooper, Jay W, Saphire, Erica Ollmann, Crowe, James E, Liu, Qiang, Axelrod, Fumiko, Sato, Aaron K
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2022; Taylor & Francis Group
• Subjects: Animals; Antibodies, Neutralizing - genetics; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - metabolism; Antibodies, Neutralizing - pharmacology; Antibodies, Viral - genetics; Antibodies, Viral - immunology; Antibodies, Viral - metabolism; Antibody Specificity; Binding Sites, Antibody; Cell Surface Display Techniques; Chlorocebus aethiops; covid-19; COVID-19 - immunology; COVID-19 - metabolism; COVID-19 - prevention & control; COVID-19 - virology; Disease Models, Animal; Epitopes; Female; Host-Pathogen Interactions; Immunoglobulin G - genetics; Immunoglobulin G - immunology; Immunoglobulin G - metabolism; Immunoglobulin G - pharmacology; Mesocricetus; neutralizing antibody; Peptide Library; sars-cov-2; SARS-CoV-2 - immunology; SARS-CoV-2 - pathogenicity; Single-Domain Antibodies - genetics; Single-Domain Antibodies - immunology; Single-Domain Antibodies - metabolism; Single-Domain Antibodies - pharmacology; spike glycoprotein; Spike Glycoprotein, Coronavirus - immunology; synthetic libraries; Vero Cells; COVID-19; neutralizing antibody; SARS-CoV-2; synthetic libraries; spike glycoprotein
• ISSN: 1942-0862; 1942-0870
• DOI: 10.1080/19420862.2021.2002236

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 , and a capacity to limit disease .