| Autor: |
Julius Hoffmann, Laura Stöffler, Christian Drosten, Ian A. Wilson, Stefan Hippenstiel, Niels von Wardenburg, Jakob Trimpert, Xueyong Zhu, Dietmar Schmitz, Scott van Hoof, Andreas C. Hocke, Florian Kurth, Marcel A. Müller, Lucie Y Li, Hejun Liu, Leif E. Sander, Christiana Franke, Daria Vladimirova, Chang-Chun D Lee, Anja Richter, Marie Luisa Schmidt, Kristina Dietert, Elisa Sanchez-Sendin, Jakob Kreye, Karl Skriner, Harald Prüss, Lara Maria Jeworowski, Martin Witzenrath, Marie A Homeyer, Nikolaus Osterrieder, Nicholas C. Wu, Daniel Wendisch, Victor M. Corman, Paula Charlotte Barthel, Matthias Endres, Luca D. Bertzbach, Azza Abdelgawad, Meng Yuan, Norbert Suttorp, S. Momsen Reincke, Markus Höltje, Tatjana Schwarz, Hans Christian Kornau, Achim D. Gruber |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Cell
Cell 183(4), 1058-1069.e19 (2020). doi:10.1016/j.cell.2020.09.049 |
| ISSN: |
1097-4172
0092-8674 |
| Popis: |
The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from ten COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb CV07-209 neutralized authentic SARS-CoV-2 with IC50 of 3.1 ng/ml. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 Å revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2 neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.
HIGHLIGHTS • Characterization of potent human monoclonal SARS-CoV-2 neutralizing antibodies • Some SARS-CoV-2 antibodies reacted with mammalian self-antigens in different organs • Crystal structures of two antibodies in complex with SARS-CoV-2 RBD at 2.55/2.70 Å • Post-exposure antibody treatment protected from lung damage in infected hamsters
Kreye et al. report the isolation and characterization of monoclonal antibodies isolated from COVID-19 patients, some of which were found to display autoreactivity with mammalian self-antigens in different organs. Crystal structures of two antibodies in complex with SARS-CoV-2 Spike RBD reveal antibody engagement with the ACE2 binding site from different approach angles. One antibody is further evaluated for in vivo efficacy and was found to be both protective and efficacious post-challenge in a hamster infection model. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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