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Cell
. 2020 Sep 23;S0092-8674(20)31246-0.
doi: 10.1016/j.cell.2020.09.049. Online ahead of print.
A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model
Jakob Kreye 1 , S Momsen Reincke 2 , Hans-Christian Kornau 3 , Elisa S?nchez-Sendin 4 , Victor Max Corman 5 , Hejun Liu 6 , Meng Yuan 6 , Nicholas C Wu 6 , Xueyong Zhu 6 , Chang-Chun D Lee 6 , Jakob Trimpert 7 , Markus H?ltje 8 , Kristina Dietert 9 , Laura St?ffler 10 , Niels von Wardenburg 10 , Scott van Hoof 4 , Marie A Homeyer 11 , Julius Hoffmann 10 , Azza Abdelgawad 7 , Achim D Gruber 12 , Luca D Bertzbach 7 , Daria Vladimirova 7 , Lucie Y Li 13 , Paula Charlotte Barthel 8 , Karl Skriner 14 , Andreas C Hocke 15 , Stefan Hippenstiel 15 , Martin Witzenrath 15 , Norbert Suttorp 15 , Florian Kurth 16 , Christiana Franke 17 , Matthias Endres 18 , Dietmar Schmitz 3 , Lara Maria Jeworowski 5 , Anja Richter 5 , Marie Luisa Schmidt 5 , Tatjana Schwarz 5 , Marcel Alexander M?ller 5 , Christian Drosten 5 , Daniel Wendisch 15 , Leif E Sander 15 , Nikolaus Osterrieder 19 , Ian A Wilson 20 , Harald Pr?ss 21
Affiliations
- PMID: 33058755
- PMCID: PMC7510528
- DOI: 10.1016/j.cell.2020.09.049
Abstract
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 10 COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb, CV07-209, neutralized authentic SARS-CoV-2 with an IC50 value 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 ? 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.
Keywords: COVID-19; SARS-CoV-2; autoreactivity; crystal structures; hamster model; monoclonal antibody; neutralizing antibody; post-exposure; self-antigens; self-reactivity.