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Discovery and characterization of high-affinity, potent SARS-CoV-2 neutralizing antibodies via single B cell screening.
Schardt, John S; Pornnoppadol, Ghasidit; Desai, Alec A; Park, Kyung Soo; Zupancic, Jennifer M; Makowski, Emily K; Smith, Matthew D; Chen, Hongwei; Garcia de Mattos Barbosa, Mayara; Cascalho, Marilia; Lanigan, Thomas M; Moon, James J; Tessier, Peter M.
  • Schardt JS; Departments of Chemical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Pornnoppadol G; Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Desai AA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Park KS; Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Zupancic JM; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Makowski EK; Departments of Chemical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Smith MD; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Chen H; Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Garcia de Mattos Barbosa M; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Cascalho M; Departments of Chemical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Lanigan TM; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Moon JJ; Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Tessier PM; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
Sci Rep ; 11(1): 20738, 2021 10 20.
Article in English | MEDLINE | ID: covidwho-1475484
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+ 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: B-Lymphocytes / Antibodies, Neutralizing / SARS-CoV-2 / COVID-19 Type of study: Diagnostic study Topics: Vaccines Limits: Animals / Female / Humans Language: English Journal: Sci Rep Year: 2021 Document Type: Article Affiliation country: S41598-021-99401-x

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Full text: Available Collection: International databases Database: MEDLINE Main subject: B-Lymphocytes / Antibodies, Neutralizing / SARS-CoV-2 / COVID-19 Type of study: Diagnostic study Topics: Vaccines Limits: Animals / Female / Humans Language: English Journal: Sci Rep Year: 2021 Document Type: Article Affiliation country: S41598-021-99401-x