1. Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms
- Author
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Ha V. Dang, Andrea Minola, Michael A. Schmid, Cindy Ng, Rana Abdelnabi, Matthew McCallum, David Veesler, Heather Tucker, Alessia Peter, Michael S. Diamond, Katja Culap, Josh Dillen, Nicole Sprugasci, Jiayi Zhou, Martin Montiel-Ruiz, Hannah Kaiser, James Brett Case, M. Alejandra Tortorici, Roberto Spreafico, Marcel Meury, Siro Bianchi, Herbert W. Virgin, Jason A. Wojcechowskyj, Elisabetta Cameroni, John E. Bowen, Agostino Riva, Fabio Benigni, G. Snell, Massimo Galli, Barbara Guarino, Martina Beltramello, Colin Havenar-Daughton, Matteo Samuele Pizzuto, Stefano Jaconi, Davide Corti, Anna De Marco, Arianna Gabrieli, Rita E. Chen, Florian A. Lempp, Laura E. Rosen, Shi Yan Caroline Foo, Elvin J. Lauron, Katja Fink, Nadine Czudnochowski, Dora Pinto, Johan Neyts, and Fabrizia Zatta
- Subjects
0301 basic medicine ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,viruses ,Protein domain ,Mutant ,Amino Acid Motifs ,Pneumonia, Viral ,Immunology ,CHO Cells ,Biology ,Peptidyl-Dipeptidase A ,Antibodies, Viral ,Epitope ,03 medical and health sciences ,Betacoronavirus ,0302 clinical medicine ,Cricetulus ,Protein Domains ,Cricetinae ,Animals ,Humans ,Pandemics ,Research Articles ,Multidisciplinary ,Immunodominant Epitopes ,SARS-CoV-2 ,Chinese hamster ovary cell ,R-Articles ,HEK 293 cells ,fungi ,Cryoelectron Microscopy ,COVID-19 ,Biochem ,biology.organism_classification ,Virology ,Antibodies, Neutralizing ,Microscopy, Electron ,030104 developmental biology ,HEK293 Cells ,Spike Glycoprotein, Coronavirus ,biology.protein ,Angiotensin-Converting Enzyme 2 ,Antibody ,Coronavirus Infections ,030217 neurology & neurosurgery ,Research Article - Abstract
A strong cocktail against SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by the trimeric spike protein that decorates the virus and binds the ACE2 receptor. Antibodies against the spike that neutralize viral infection have potential as therapeutics. Tortorici et al. describe two very potent antibodies, S2E12 and S2M11. Electron microscopy structures characterized the binding and showed that S2E12 traps the spike in a conformation that cannot bind ACE2. Both antibodies protected hamsters against SARS-CoV-2 challenge and may be useful in antibody cocktails to combat the virus and prevent the development of resistance. Science, this issue p. 950, A potent antibody cocktail blocks attachment of SARS-CoV-2 to the host receptor and activates a protective immune response., 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.
- Published
- 2020