학술논문
Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms
CORONAVIRUS
CORONAVIRUS
Document Type
Academic Journal
Author
Tortorici, M. Alejandra; Beltramello, Martina; Lempp, Florian A.; Pinto, Dora; Dang, Ha V.; Rosen, Laura E.; McCallum, Matthew; Bowen, John; Minola, Andrea; Jaconi, Stefano; Zatta, Fabrizia; De Marco, Anna; Guarino, Barbara; Bianchi, Siro; Lauron, Elvin J.; Tucker, Heather; Zhou, Jiayi; Peter, Alessia; Havenar-Daughton, Colin; Wojcechowskyj, Jason A.; Case, James Brett; Chen, Rita E.; Kaiser, Hannah; Montiel-Ruiz, Martin; Meury, Marcel; Czudnochowski, Nadine; Spreafico, Roberto; Dillen, Josh; Ng, Cindy; Sprugasci, Nicole; Culap, Katja; Benigni, Fabio; Abdelnabi, Rana; Foo, Shi-Yan Caroline; Schmid, Michael A.; Cameroni, Elisabetta; Riva, Agostino; Gabrieli, Arianna; Galli, Massimo; Pizzuto, Matteo S.; Neyts, Johan; Diamond, Michael S.; Virgin, Herbert W.; Snell, Gyorgy; Corti, Davide; Fink, Katja; Veesler, David
Source
Science. Nov 20, 2020, Vol. 370 Issue 6519, p950, 8 p.
Subject
Language
English
ISSN
0036-8075
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.