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.

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.