Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

• Published in: Science (American Association for the Advancement of Science) Vol. 369; no. 6506; pp. 956 - 963
• Main Authors: Rogers, Thomas F., Zhao, Fangzhu, Huang, Deli, Beutler, Nathan, Burns, Alison, He, Wan-ting, Limbo, Oliver, Smith, Chloe, Song, Ge, Woehl, Jordan, Yang, Linlin, Abbott, Robert K., Callaghan, Sean, Garcia, Elijah, Hurtado, Jonathan, Parren, Mara, Peng, Linghang, Ramirez, Sydney, Ricketts, James, Ricciardi, Michael J., Rawlings, Stephen A., Wu, Nicholas C., Yuan, Meng, Smith, Davey M., Nemazee, David, Teijaro, John R., Voss, James E., Wilson, Ian A., Andrabi, Raiees, Briney, Bryan, Landais, Elise, Sok, Devin, Jardine, Joseph G., Burton, Dennis R.
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 21.08.2020; American Association for the Advancement of Science
• Subjects: ACE2; Adult; Angiotensin; Angiotensin-Converting Enzyme 2; Animal diseases; Animal models; Animals; Antibodies; Antibodies, Monoclonal - blood; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - isolation & purification; Antibodies, Monoclonal - therapeutic use; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - isolation & purification; Antibodies, Neutralizing - therapeutic use; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antibodies, Viral - isolation & purification; Antibodies, Viral - therapeutic use; Antibody Affinity; Antibody Specificity; Betacoronavirus - immunology; Betacoronavirus - physiology; Binding Sites; Cell Line; Coronaviridae; Coronavirus Infections - immunology; Coronavirus Infections - prevention & control; Coronavirus Infections - therapy; Coronavirus Infections - virology; Coronaviruses; COVID-19; COVID-19 Serotherapy; Disease Models, Animal; Domains; Epitopes; Female; Global health; Hamsters; Humans; Immunization, Passive; Immunology; Lung - virology; Male; Mesocricetus; Microbio; Middle Aged; Model testing; Monoclonal antibodies; Neutralization; Neutralization Tests; Neutralizing; Pandemics - prevention & control; Peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - metabolism; Pneumonia, Viral - immunology; Pneumonia, Viral - prevention & control; Pneumonia, Viral - therapy; Pneumonia, Viral - virology; Prophylaxis; Protein Domains; Proteins; Receptors; Respiratory diseases; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; Spike protein; Viral diseases; Viral Load; Virus Replication
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.abc7520

Antibodies produced by survivors of coronavirus disease 2019 (COVID-19) may be leveraged to develop therapies. A first step is identifying neutralizing antibodies, which confer strong protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rogers et al. used a high-throughput pipeline to isolate and characterize monoclonal antibodies from convalescent donors. Antibodies were selected for binding to the viral spike protein, which facilitates entry into host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Most isolated antibodies bound to regions of the spike outside of the receptor binding domain (RBD); however, a larger proportion of the RBD-binding antibodies were neutralizing, with the most potent binding at a site that overlaps the ACE2 binding site. Two of the neutralizing antibodies were tested in Syrian hamsters and provided protection against SARS-CoV-2 infection. Science , this issue p. 956 Passive transfer of a neutralizing antibody provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design.