Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody

• Published in: Nature (London) Vol. 583; no. 7815; pp. 290 - 295
• Main Authors: Pinto, Dora, Park, Young-Jun, Beltramello, Martina, Walls, Alexandra C., Tortorici, M. Alejandra, Bianchi, Siro, Jaconi, Stefano, Culap, Katja, Zatta, Fabrizia, De Marco, Anna, Peter, Alessia, Guarino, Barbara, Spreafico, Roberto, Cameroni, Elisabetta, Case, James Brett, Chen, Rita E., Havenar-Daughton, Colin, Snell, Gyorgy, Telenti, Amalio, Virgin, Herbert W., Lanzavecchia, Antonio, Diamond, Michael S., Fink, Katja, Veesler, David, Corti, Davide
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.07.2020; Nature Publishing Group
• Subjects: 101/28; 13/1; 13/31; 631/250/255/2514; 631/326/596/4130; 631/61/51/1568; Angiotensin-Converting Enzyme 2; Animals; Antibodies; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antibodies, Neutralizing - chemistry; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - pharmacology; Antibodies, Viral - chemistry; Antibodies, Viral - immunology; Antibodies, Viral - pharmacology; Antibody-Dependent Cell Cytotoxicity - drug effects; Antibody-Dependent Cell Cytotoxicity - immunology; B-Lymphocytes - immunology; Betacoronavirus - chemistry; Betacoronavirus - drug effects; Betacoronavirus - immunology; Binding; Chlorocebus aethiops; Coronaviridae; Coronavirus Infections - immunology; Coronavirus Infections - prevention & control; Coronavirus Infections - therapy; Coronavirus Infections - virology; Coronaviruses; COVID-19; Cross Reactions - drug effects; Cross Reactions - immunology; Cryoelectron Microscopy; Disease transmission; Electron microscopy; Enzymes; Epidemics; Epitopes; Epitopes, B-Lymphocyte - chemistry; Epitopes, B-Lymphocyte - immunology; Glycan; Glycoproteins; HEK293 Cells; Humanities and Social Sciences; Humans; Immune Evasion - immunology; Immunoglobulin Fab Fragments - chemistry; Immunoglobulin Fab Fragments - immunology; Immunoglobulin Fab Fragments - pharmacology; Immunologic Memory - immunology; Immunological memory; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Life Sciences; Lymphocytes B; Memory cells; Microscopy; Middle East respiratory syndrome; Models, Molecular; Monoclonal antibodies; multidisciplinary; Neutralization; Neutralization Tests; Pandemics; Pandemics - prevention & control; Peptidyl-Dipeptidase A - chemistry; Peptidyl-Dipeptidase A - metabolism; Pneumonia, Viral - immunology; Pneumonia, Viral - prevention & control; Pneumonia, Viral - therapy; Pneumonia, Viral - virology; Prophylaxis; Receptors; Respiratory diseases; Sarbecovirus; SARS Virus - chemistry; SARS Virus - drug effects; SARS Virus - immunology; SARS-CoV-2; Science; Science (multidisciplinary); Severe Acute Respiratory Syndrome - immunology; Severe Acute Respiratory Syndrome - virology; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - immunology; Vaccines; Vero Cells; Viral diseases; Viruses; Zoonoses
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-020-2349-y

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 2020 1 , 2 . Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which we identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. One antibody (named S309) potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2, by engaging the receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, we show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies that we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease. The monoclonal antibody S309, identified from memory B cells of an individual infected with SARS-CoV in 2003, or antibody cocktails that contain this antibody potently neutralize SARS-CoV-2.