Development of neutralizing antibodies against SARS-CoV-2, using a high-throughput single-B-cell cloning method.

Background:Rapid and efficient strategies are needed to discover neutralizing antibodies (nAbs) from B cells derived from virus-infected patients. Methods:Here, we report a high-throughput single-B-cell cloning method for high-throughput isolation of nAbs targeting diverse epitopes on the SARS-CoV-2-RBD (receptor binding domain) from convalescent COVID-19 patients. This method is simple, fast and highly efficient in generating SARS-CoV-2-neutralizing antibodies from COVID-19 patients' B cells. Results:Using this method, we have developed multiple nAbs against distinct SARS-CoV-2-RBD epitopes. CryoEM and crystallography revealed precisely how they bind RBD. In live virus assay, these nAbs are effective in blocking viral entry to the host cells. Conclusion:This simple and efficient method may be useful in developing human therapeutic antibodies for other diseases and next pandemic.