Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects

• Published in: Cell reports (Cambridge) Vol. 36; no. 2; p. 109353
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.07.2021; Elsevier; Cell Press
• Subjects: 60 APPLIED LIFE SCIENCES; Angiotensin-Converting Enzyme 2 - chemistry; Angiotensin-Converting Enzyme 2 - immunology; Animals; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - immunology; Antibodies, Viral - chemistry; Antibodies, Viral - immunology; B.1.351; Binding Sites; Cell Line; COVID-19 - immunology; COVID-19 - prevention & control; Cross Reactions; CV3-25; Epitopes - immunology; Female; HEK293 Cells; Humans; Mice; monoclonal antibodies; neutralization; Neutralization Tests; NTD; Protein Binding - immunology; Protein Domains; RBD; S2 subunit; SARS-CoV-1; SARS-CoV-2; SARS-CoV-2 - immunology; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - immunology; S2 subunit; SARS-CoV-2; SARS-CoV-1; B.1.351; RBD; neutralization; CV3-25; NTD; monoclonal antibodies
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.109353

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 characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize 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 neutralize 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. [Display omitted] •Fourteen anti-SARS-CoV-2 neutralizing mAbs isolated from four patients•Three anti-RBD and one anti-S2 mAb neutralized SARS-CoV-1 and the B.1.351 variant•Mouse studies show potential protective effect of anti-NTD mAbs Jennewein et al. isolated 14 anti-SARS-CoV-2 neutralizing antibodies—one anti-S2, one anti-NTD, and 11 anti-RBD—from four patients. Three anti-RBD and the anti-S2 nAbs cross-neutralized SARS-CoV-1 and B.1.351. The anti-NTD mAbs conferred partial protection in mice. Evolved anti-S2 Abs may provide templates for pan-coronavirus vaccines.