Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.

Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms / M.A. Tortorici, M. Beltramello, F.A. Lempp, D. Pinto, H.V. Dang, L.E. Rosen, M. McCallum, J. Bowen, A. Minola, S. Jaconi, F. Zatta, A. De Marco, B. Guarino, S. Bianchi, E.J. Lauron, H. Tucker, J. Zhou, A. Peter, C. Havenar-Daughton, J.A. Wojcechowskyj, J.B. Case, R.E. Chen, H. Kaiser, M. Montiel-Ruiz, M. Meury, N. Czudnochowski, R. Spreafico, J. Dillen, C. Ng, N. Sprugasci, K. Culap, F. Benigni, R. Abdelnabi, S.-.C. Foo, M.A. Schmid, E. Cameroni, A. Riva, A. Gabrieli, M. Galli, M.S. Pizzuto, J. Neyts, M.S. Diamond, H.W. Virgin, G. Snell, D. Corti, K. Fink, D. Veesler. - In: SCIENCE. - ISSN 0036-8075. - 370:6519(2020), pp. 950-957. [10.1126/science.abe3354]

Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms

A. Riva;A. Gabrieli;M. Galli;
2020

Abstract

Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.
Amino Acid Motifs; Angiotensin-Converting Enzyme 2; Animals; Antibodies, Neutralizing; Antibodies, Viral; Betacoronavirus; CHO Cells; COVID-19; Coronavirus Infections; Cricetinae; Cricetulus; Cryoelectron Microscopy; HEK293 Cells; Humans; Immunodominant Epitopes; Microscopy, Electron; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protein Domains; SARS-CoV-2; Spike Glycoprotein, Coronavirus
Settore MED/17 - Malattie Infettive
Article (author)
File in questo prodotto:
File Dimensione Formato  
science.abe3354.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 1.46 MB
Formato Adobe PDF
1.46 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/861709
Citazioni
  • ???jsp.display-item.citation.pmc??? 212
  • Scopus 246
  • ???jsp.display-item.citation.isi??? 235
social impact