tetano
Editor, Senior Moderator
MAbs
. Jan-Dec 2022;14(1):2002236.
doi: 10.1080/19420862.2021.2002236.
Rapid discovery of diverse neutralizing SARS-CoV-2 antibodies from large-scale synthetic phage libraries
Tom Z Yuan[SUP] 1 [/SUP], Pankaj Garg[SUP] 2 [/SUP], Linya Wang[SUP] 1 [/SUP], Jordan R Willis[SUP] 3 [/SUP], Eric Kwan[SUP] 1 [/SUP], Ana G Lujan Hernandez[SUP] 1 [/SUP], Emily Tuscano[SUP] 1 [/SUP], Emily N Sever[SUP] 1 [/SUP], Erica Keane[SUP] 4 [/SUP], Cinque Soto[SUP] 5 [/SUP], Eric M Mucker[SUP] 6 [/SUP], Mallorie E Fouch[SUP] 7 [/SUP], Edgar Davidson[SUP] 7 [/SUP], Benjamin J Doranz[SUP] 7 [/SUP], Shweta Kailasan[SUP] 8 [/SUP], M Javad Aman[SUP] 8 [/SUP], Haoyang Li[SUP] 9 [/SUP], Jay W Hooper[SUP] 6 [/SUP], Erica Ollmann Saphire[SUP] 9 10 [/SUP], James E Crowe[SUP] 5 11 12 [/SUP], Qiang Liu[SUP] 1 [/SUP], Fumiko Axelrod[SUP] 1 [/SUP], Aaron K Sato[SUP] 1 [/SUP]
Affiliations
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.
Keywords: COVID-19; SARS-CoV-2; neutralizing antibody; spike glycoprotein; synthetic libraries.
. Jan-Dec 2022;14(1):2002236.
doi: 10.1080/19420862.2021.2002236.
Rapid discovery of diverse neutralizing SARS-CoV-2 antibodies from large-scale synthetic phage libraries
Tom Z Yuan[SUP] 1 [/SUP], Pankaj Garg[SUP] 2 [/SUP], Linya Wang[SUP] 1 [/SUP], Jordan R Willis[SUP] 3 [/SUP], Eric Kwan[SUP] 1 [/SUP], Ana G Lujan Hernandez[SUP] 1 [/SUP], Emily Tuscano[SUP] 1 [/SUP], Emily N Sever[SUP] 1 [/SUP], Erica Keane[SUP] 4 [/SUP], Cinque Soto[SUP] 5 [/SUP], Eric M Mucker[SUP] 6 [/SUP], Mallorie E Fouch[SUP] 7 [/SUP], Edgar Davidson[SUP] 7 [/SUP], Benjamin J Doranz[SUP] 7 [/SUP], Shweta Kailasan[SUP] 8 [/SUP], M Javad Aman[SUP] 8 [/SUP], Haoyang Li[SUP] 9 [/SUP], Jay W Hooper[SUP] 6 [/SUP], Erica Ollmann Saphire[SUP] 9 10 [/SUP], James E Crowe[SUP] 5 11 12 [/SUP], Qiang Liu[SUP] 1 [/SUP], Fumiko Axelrod[SUP] 1 [/SUP], Aaron K Sato[SUP] 1 [/SUP]
Affiliations
- PMID: 34967699
- DOI: 10.1080/19420862.2021.2002236
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.
Keywords: COVID-19; SARS-CoV-2; neutralizing antibody; spike glycoprotein; synthetic libraries.