Isolation and Characterization of Cross-Neutralizing Coronavirus Antibodies from COVID-19+ Subjects

Jennewein, Madeleine F.; MacCamy, Anna J.; Akins, Nicholas R.; Feng, Junli; Homad, Leah J.; Hurlburt, Nicholas K.; Seydoux, Emilie; Wan, Yu-Hsin; Stuart, Andrew B.; Edara, Venkata Viswanadh; Floyd, Katharine; Vanderheiden, Abigail; Mascola, John R.; Doria-Rose, Nicole; Wang, Lingshu; Yang, Eun Sung; Chu, Helen Y.; Torres, Jonathan L.; Ozorowski, Gabriel; Ward, Andrew B.; Whaley, Rachael E.; Cohen, Kristen W.; Pancera, Marie; McElrath, M. Juliana; Englund, Janet A.; Finzi, Andrés; Suthar, Mehul S.; McGuire, Andrew T.; Stamatatos, Leonidas

SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterized 198 antibodies isolated from four COVID19+ subjects and identified 14 SARS-CoV-2 neutralizing antibodies. One targeted the NTD, one recognized an epitope in S2 and eleven bound the RBD. Three anti-RBD neutralizing antibodies cross-neutralized SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralized the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.