1. Rapid discovery of diverse neutralizing SARS-CoV-2 antibodies from large-scale synthetic phage libraries.
- Author
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Yuan TZ, Garg P, Wang L, Willis JR, Kwan E, Hernandez AGL, Tuscano E, Sever EN, Keane E, Soto C, Mucker EM, Fouch ME, Davidson E, Doranz BJ, Kailasan S, Aman MJ, Li H, Hooper JW, Saphire EO, Crowe JE, Liu Q, Axelrod F, and Sato AK
- Subjects
- Animals, Antibodies, Neutralizing genetics, Antibodies, Neutralizing metabolism, Antibodies, Neutralizing pharmacology, Antibodies, Viral genetics, Antibodies, Viral metabolism, Antibody Specificity, Binding Sites, Antibody, COVID-19 metabolism, COVID-19 prevention & control, COVID-19 virology, Chlorocebus aethiops, Disease Models, Animal, Epitopes, Female, Host-Pathogen Interactions, Immunoglobulin G genetics, Immunoglobulin G metabolism, Immunoglobulin G pharmacology, Mesocricetus, SARS-CoV-2 pathogenicity, Single-Domain Antibodies genetics, Single-Domain Antibodies metabolism, Single-Domain Antibodies pharmacology, Vero Cells, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, COVID-19 immunology, Cell Surface Display Techniques, Immunoglobulin G immunology, Peptide Library, SARS-CoV-2 immunology, Single-Domain Antibodies immunology, Spike Glycoprotein, Coronavirus immunology
- Abstract
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 .
- Published
- 2022
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