tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], S Momsen Reincke[SUP] 2 [/SUP], Hans-Christian Kornau[SUP] 3 [/SUP], Elisa S?nchez-Sendin[SUP] 4 [/SUP], Victor Max Corman[SUP] 5 [/SUP], Hejun Liu[SUP] 6 [/SUP], Meng Yuan[SUP] 6 [/SUP], Nicholas C Wu[SUP] 6 [/SUP], Xueyong Zhu[SUP] 6 [/SUP], Chang-Chun D Lee[SUP] 6 [/SUP], Jakob Trimpert[SUP] 7 [/SUP], Markus H?ltje[SUP] 8 [/SUP], Kristina Dietert[SUP] 9 [/SUP], Laura St?ffler[SUP] 10 [/SUP], Niels von Wardenburg[SUP] 10 [/SUP], Scott van Hoof[SUP] 4 [/SUP], Marie A Homeyer[SUP] 11 [/SUP], Julius Hoffmann[SUP] 10 [/SUP], Azza Abdelgawad[SUP] 7 [/SUP], Achim D Gruber[SUP] 12 [/SUP], Luca D Bertzbach[SUP] 7 [/SUP], Daria Vladimirova[SUP] 7 [/SUP], Lucie Y Li[SUP] 13 [/SUP], Paula Charlotte Barthel[SUP] 8 [/SUP], Karl Skriner[SUP] 14 [/SUP], Andreas C Hocke[SUP] 15 [/SUP], Stefan Hippenstiel[SUP] 15 [/SUP], Martin Witzenrath[SUP] 15 [/SUP], Norbert Suttorp[SUP] 15 [/SUP], Florian Kurth[SUP] 16 [/SUP], Christiana Franke[SUP] 17 [/SUP], Matthias Endres[SUP] 18 [/SUP], Dietmar Schmitz[SUP] 3 [/SUP], Lara Maria Jeworowski[SUP] 5 [/SUP], Anja Richter[SUP] 5 [/SUP], Marie Luisa Schmidt[SUP] 5 [/SUP], Tatjana Schwarz[SUP] 5 [/SUP], Marcel Alexander M?ller[SUP] 5 [/SUP], Christian Drosten[SUP] 5 [/SUP], Daniel Wendisch[SUP] 15 [/SUP], Leif E Sander[SUP] 15 [/SUP], Nikolaus Osterrieder[SUP] 19 [/SUP], Ian A Wilson[SUP] 20 [/SUP], Harald Pr?ss[SUP] 21 [/SUP]
Affiliations
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 IC[SUB]50[/SUB] 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.
. 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[SUP] 1 [/SUP], S Momsen Reincke[SUP] 2 [/SUP], Hans-Christian Kornau[SUP] 3 [/SUP], Elisa S?nchez-Sendin[SUP] 4 [/SUP], Victor Max Corman[SUP] 5 [/SUP], Hejun Liu[SUP] 6 [/SUP], Meng Yuan[SUP] 6 [/SUP], Nicholas C Wu[SUP] 6 [/SUP], Xueyong Zhu[SUP] 6 [/SUP], Chang-Chun D Lee[SUP] 6 [/SUP], Jakob Trimpert[SUP] 7 [/SUP], Markus H?ltje[SUP] 8 [/SUP], Kristina Dietert[SUP] 9 [/SUP], Laura St?ffler[SUP] 10 [/SUP], Niels von Wardenburg[SUP] 10 [/SUP], Scott van Hoof[SUP] 4 [/SUP], Marie A Homeyer[SUP] 11 [/SUP], Julius Hoffmann[SUP] 10 [/SUP], Azza Abdelgawad[SUP] 7 [/SUP], Achim D Gruber[SUP] 12 [/SUP], Luca D Bertzbach[SUP] 7 [/SUP], Daria Vladimirova[SUP] 7 [/SUP], Lucie Y Li[SUP] 13 [/SUP], Paula Charlotte Barthel[SUP] 8 [/SUP], Karl Skriner[SUP] 14 [/SUP], Andreas C Hocke[SUP] 15 [/SUP], Stefan Hippenstiel[SUP] 15 [/SUP], Martin Witzenrath[SUP] 15 [/SUP], Norbert Suttorp[SUP] 15 [/SUP], Florian Kurth[SUP] 16 [/SUP], Christiana Franke[SUP] 17 [/SUP], Matthias Endres[SUP] 18 [/SUP], Dietmar Schmitz[SUP] 3 [/SUP], Lara Maria Jeworowski[SUP] 5 [/SUP], Anja Richter[SUP] 5 [/SUP], Marie Luisa Schmidt[SUP] 5 [/SUP], Tatjana Schwarz[SUP] 5 [/SUP], Marcel Alexander M?ller[SUP] 5 [/SUP], Christian Drosten[SUP] 5 [/SUP], Daniel Wendisch[SUP] 15 [/SUP], Leif E Sander[SUP] 15 [/SUP], Nikolaus Osterrieder[SUP] 19 [/SUP], Ian A Wilson[SUP] 20 [/SUP], Harald Pr?ss[SUP] 21 [/SUP]
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 IC[SUB]50[/SUB] 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.