National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM120553
引用
ジャーナル: Science / 年: 2020 タイトル: Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms. 著者: M Alejandra Tortorici / Martina Beltramello / Florian A Lempp / Dora Pinto / Ha V Dang / Laura E Rosen / Matthew McCallum / John Bowen / Andrea Minola / Stefano Jaconi / Fabrizia Zatta / Anna ...著者: M Alejandra Tortorici / Martina Beltramello / Florian A Lempp / Dora Pinto / Ha V Dang / Laura E Rosen / Matthew McCallum / John Bowen / Andrea Minola / Stefano Jaconi / Fabrizia Zatta / Anna De Marco / Barbara Guarino / Siro Bianchi / Elvin J Lauron / Heather Tucker / Jiayi Zhou / Alessia Peter / Colin Havenar-Daughton / Jason A Wojcechowskyj / James Brett Case / Rita E Chen / Hannah Kaiser / Martin Montiel-Ruiz / Marcel Meury / Nadine Czudnochowski / Roberto Spreafico / Josh Dillen / Cindy Ng / Nicole Sprugasci / Katja Culap / Fabio Benigni / Rana Abdelnabi / Shi-Yan Caroline Foo / Michael A Schmid / Elisabetta Cameroni / Agostino Riva / Arianna Gabrieli / Massimo Galli / Matteo S Pizzuto / Johan Neyts / Michael S Diamond / Herbert W Virgin / Gyorgy Snell / Davide Corti / Katja Fink / David Veesler / 要旨: 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 ...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.