tetano
Editor, Senior Moderator
Sci Rep
. 2021 Oct 20;11(1):20738.
doi: 10.1038/s41598-021-99401-x.
Discovery and characterization of high-affinity, potent SARS-CoV-2 neutralizing antibodies via single B cell screening
John S Schardt[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Ghasidit Pornnoppadol[SUP] #[/SUP][SUP] 2 3 [/SUP], Alec A Desai[SUP] 1 3 [/SUP], Kyung Soo Park[SUP] 4 3 [/SUP], Jennifer M Zupancic[SUP] 1 3 [/SUP], Emily K Makowski[SUP] 2 3 [/SUP], Matthew D Smith[SUP] 1 3 [/SUP], Hongwei Chen[SUP] 1 2 3 [/SUP], Mayara Garcia de Mattos Barbosa[SUP] 5 [/SUP], Marilia Cascalho[SUP] 5 6 [/SUP], Thomas M Lanigan[SUP] 7 [/SUP], James J Moon[SUP] 2 4 3 [/SUP], Peter M Tessier[SUP] 8 9 10 11 12 [/SUP]
Affiliations
Abstract
Monoclonal antibodies that target SARS-CoV-2 with high affinity are valuable for a wide range of biomedical applications involving novel coronavirus disease (COVID-19) diagnosis, treatment, and prophylactic intervention. Strategies for the rapid and reliable isolation of these antibodies, especially potent neutralizing antibodies, are critical toward improved COVID-19 response and informed future response to emergent infectious diseases. In this study, single B cell screening was used to interrogate antibody repertoires of immunized mice and isolate antigen-specific IgG1[SUP]+[/SUP] memory B cells. Using these methods, high-affinity, potent neutralizing antibodies were identified that target the receptor-binding domain of SARS-CoV-2. Further engineering of the identified molecules to increase valency resulted in enhanced neutralizing activity. Mechanistic investigation revealed that these antibodies compete with ACE2 for binding to the receptor-binding domain of SARS-CoV-2. These antibodies may warrant further development for urgent COVID-19 applications. Overall, these results highlight the potential of single B cell screening for the rapid and reliable identification of high-affinity, potent neutralizing antibodies for infectious disease applications.
. 2021 Oct 20;11(1):20738.
doi: 10.1038/s41598-021-99401-x.
Discovery and characterization of high-affinity, potent SARS-CoV-2 neutralizing antibodies via single B cell screening
John S Schardt[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Ghasidit Pornnoppadol[SUP] #[/SUP][SUP] 2 3 [/SUP], Alec A Desai[SUP] 1 3 [/SUP], Kyung Soo Park[SUP] 4 3 [/SUP], Jennifer M Zupancic[SUP] 1 3 [/SUP], Emily K Makowski[SUP] 2 3 [/SUP], Matthew D Smith[SUP] 1 3 [/SUP], Hongwei Chen[SUP] 1 2 3 [/SUP], Mayara Garcia de Mattos Barbosa[SUP] 5 [/SUP], Marilia Cascalho[SUP] 5 6 [/SUP], Thomas M Lanigan[SUP] 7 [/SUP], James J Moon[SUP] 2 4 3 [/SUP], Peter M Tessier[SUP] 8 9 10 11 12 [/SUP]
Affiliations
- PMID: 34671080
- DOI: 10.1038/s41598-021-99401-x
Abstract
Monoclonal antibodies that target SARS-CoV-2 with high affinity are valuable for a wide range of biomedical applications involving novel coronavirus disease (COVID-19) diagnosis, treatment, and prophylactic intervention. Strategies for the rapid and reliable isolation of these antibodies, especially potent neutralizing antibodies, are critical toward improved COVID-19 response and informed future response to emergent infectious diseases. In this study, single B cell screening was used to interrogate antibody repertoires of immunized mice and isolate antigen-specific IgG1[SUP]+[/SUP] memory B cells. Using these methods, high-affinity, potent neutralizing antibodies were identified that target the receptor-binding domain of SARS-CoV-2. Further engineering of the identified molecules to increase valency resulted in enhanced neutralizing activity. Mechanistic investigation revealed that these antibodies compete with ACE2 for binding to the receptor-binding domain of SARS-CoV-2. These antibodies may warrant further development for urgent COVID-19 applications. Overall, these results highlight the potential of single B cell screening for the rapid and reliable identification of high-affinity, potent neutralizing antibodies for infectious disease applications.