Analysis of a SARS-CoV-2 infected individual reveals development of potent neutralizing antibodies to distinct epitopes with limited somatic mutation

Seydoux, Emilie; Homad, Leah J.; MacCamy, Anna J.; Parks, K. Rachael; Hurlburt, Nicholas K.; Jennewein, Madeleine F.; Akins, Nicholas R.; Stuart, Andrew B.; Wan, Yu-Hsin; Feng, Junli; Whaley, Rachael E.; Singh, Suruchi; Boeckh, Michael; Cohen, Kristen W.; McElrath, M. Juliana; Englund, Janet A.; Chu, Helen Y.; Pancera, Marie; McGuire, Andrew T.; Stamatatos, Leonidas

Abstract Antibody responses develop following SARS-CoV-2 infection, but little is known about their epitope specificities, clonality, binding affinities, epitopes and neutralizing activity. We isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject twenty-one days after the onset of clinical disease. Forty-five S-specific monoclonal antibodies were generated. They had undergone minimal somatic mutation, with limited clonal expansion and three bound the receptor binding domain (RBD). Two antibodies neutralized SARS-CoV-2. The most potent antibody bound the RBD and prevented binding to the ACE2 receptor, while the other bound outside the RBD. Thus, most anti-S antibodies that were generated in this patient during the first weeks of COVID-19 infection were non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 S-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive and/or therapeutic potential and can serve as templates for vaccine-design.