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A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model

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A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model. / Kreye, Jakob; Reincke, S Momsen; Kornau, Hans-Christian; Sánchez-Sendin, Elisa; Corman, Victor Max; Liu, Hejun; Yuan, Meng; Wu, Nicholas C; Zhu, Xueyong; Lee, Chang-Chun D; Trimpert, Jakob; Höltje, Markus; Dietert, Kristina; Stöffler, Laura; von Wardenburg, Niels; van Hoof, Scott; Homeyer, Marie A; Hoffmann, Julius; Abdelgawad, Azza; Gruber, Achim D; Bertzbach, Luca D; Vladimirova, Daria; Li, Lucie Y; Barthel, Paula Charlotte; Skriner, Karl; Hocke, Andreas C; Hippenstiel, Stefan; Witzenrath, Martin; Suttorp, Norbert; Kurth, Florian; Franke, Christiana; Endres, Matthias; Schmitz, Dietmar; Jeworowski, Lara Maria; Richter, Anja; Schmidt, Marie Luisa; Schwarz, Tatjana; Müller, Marcel Alexander; Drosten, Christian; Wendisch, Daniel; Sander, Leif E; Osterrieder, Nikolaus; Wilson, Ian A; Prüss, Harald.

in: CELL, Jahrgang 183, Nr. 4, 12.11.2020, S. 1058-1069.e19.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Kreye, J, Reincke, SM, Kornau, H-C, Sánchez-Sendin, E, Corman, VM, Liu, H, Yuan, M, Wu, NC, Zhu, X, Lee, C-CD, Trimpert, J, Höltje, M, Dietert, K, Stöffler, L, von Wardenburg, N, van Hoof, S, Homeyer, MA, Hoffmann, J, Abdelgawad, A, Gruber, AD, Bertzbach, LD, Vladimirova, D, Li, LY, Barthel, PC, Skriner, K, Hocke, AC, Hippenstiel, S, Witzenrath, M, Suttorp, N, Kurth, F, Franke, C, Endres, M, Schmitz, D, Jeworowski, LM, Richter, A, Schmidt, ML, Schwarz, T, Müller, MA, Drosten, C, Wendisch, D, Sander, LE, Osterrieder, N, Wilson, IA & Prüss, H 2020, 'A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model', CELL, Jg. 183, Nr. 4, S. 1058-1069.e19. https://doi.org/10.1016/j.cell.2020.09.049

APA

Kreye, J., Reincke, S. M., Kornau, H-C., Sánchez-Sendin, E., Corman, V. M., Liu, H., Yuan, M., Wu, N. C., Zhu, X., Lee, C-C. D., Trimpert, J., Höltje, M., Dietert, K., Stöffler, L., von Wardenburg, N., van Hoof, S., Homeyer, M. A., Hoffmann, J., Abdelgawad, A., ... Prüss, H. (2020). A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model. CELL, 183(4), 1058-1069.e19. https://doi.org/10.1016/j.cell.2020.09.049

Vancouver

Kreye J, Reincke SM, Kornau H-C, Sánchez-Sendin E, Corman VM, Liu H et al. A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model. CELL. 2020 Nov 12;183(4):1058-1069.e19. https://doi.org/10.1016/j.cell.2020.09.049

Bibtex

@article{f4c7c702631c42a5a096ba447a0c3219,
title = "A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model",
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 {\AA} 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 = "Angiotensin-Converting Enzyme 2, Animals, Antibodies, Monoclonal/immunology, Antibodies, Neutralizing/immunology, Antibodies, Viral/immunology, Antigen-Antibody Reactions, Betacoronavirus/immunology, Binding Sites, COVID-19, Coronavirus Infections/drug therapy, Cricetinae, Crystallography, X-Ray, Disease Models, Animal, Humans, Kinetics, Lung/immunology, Mice, Mice, Inbred C57BL, Molecular Dynamics Simulation, Pandemics, Peptidyl-Dipeptidase A/chemistry, Pneumonia, Viral/drug therapy, Protein Binding, SARS-CoV-2, Spike Glycoprotein, Coronavirus/chemistry",
author = "Jakob Kreye and Reincke, {S Momsen} and Hans-Christian Kornau and Elisa S{\'a}nchez-Sendin and Corman, {Victor Max} and Hejun Liu and Meng Yuan and Wu, {Nicholas C} and Xueyong Zhu and Lee, {Chang-Chun D} and Jakob Trimpert and Markus H{\"o}ltje and Kristina Dietert and Laura St{\"o}ffler and {von Wardenburg}, Niels and {van Hoof}, Scott and Homeyer, {Marie A} and Julius Hoffmann and Azza Abdelgawad and Gruber, {Achim D} and Bertzbach, {Luca D} and Daria Vladimirova and Li, {Lucie Y} and Barthel, {Paula Charlotte} and Karl Skriner and Hocke, {Andreas C} and Stefan Hippenstiel and Martin Witzenrath and Norbert Suttorp and Florian Kurth and Christiana Franke and Matthias Endres and Dietmar Schmitz and Jeworowski, {Lara Maria} and Anja Richter and Schmidt, {Marie Luisa} and Tatjana Schwarz and M{\"u}ller, {Marcel Alexander} and Christian Drosten and Daniel Wendisch and Sander, {Leif E} and Nikolaus Osterrieder and Wilson, {Ian A} and Harald Pr{\"u}ss",
note = "Copyright {\textcopyright} 2020 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2020",
month = nov,
day = "12",
doi = "10.1016/j.cell.2020.09.049",
language = "English",
volume = "183",
pages = "1058--1069.e19",
journal = "CELL",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model

AU - Kreye, Jakob

AU - Reincke, S Momsen

AU - Kornau, Hans-Christian

AU - Sánchez-Sendin, Elisa

AU - Corman, Victor Max

AU - Liu, Hejun

AU - Yuan, Meng

AU - Wu, Nicholas C

AU - Zhu, Xueyong

AU - Lee, Chang-Chun D

AU - Trimpert, Jakob

AU - Höltje, Markus

AU - Dietert, Kristina

AU - Stöffler, Laura

AU - von Wardenburg, Niels

AU - van Hoof, Scott

AU - Homeyer, Marie A

AU - Hoffmann, Julius

AU - Abdelgawad, Azza

AU - Gruber, Achim D

AU - Bertzbach, Luca D

AU - Vladimirova, Daria

AU - Li, Lucie Y

AU - Barthel, Paula Charlotte

AU - Skriner, Karl

AU - Hocke, Andreas C

AU - Hippenstiel, Stefan

AU - Witzenrath, Martin

AU - Suttorp, Norbert

AU - Kurth, Florian

AU - Franke, Christiana

AU - Endres, Matthias

AU - Schmitz, Dietmar

AU - Jeworowski, Lara Maria

AU - Richter, Anja

AU - Schmidt, Marie Luisa

AU - Schwarz, Tatjana

AU - Müller, Marcel Alexander

AU - Drosten, Christian

AU - Wendisch, Daniel

AU - Sander, Leif E

AU - Osterrieder, Nikolaus

AU - Wilson, Ian A

AU - Prüss, Harald

N1 - Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2020/11/12

Y1 - 2020/11/12

N2 - 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 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.

AB - 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 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.

KW - Angiotensin-Converting Enzyme 2

KW - Animals

KW - Antibodies, Monoclonal/immunology

KW - Antibodies, Neutralizing/immunology

KW - Antibodies, Viral/immunology

KW - Antigen-Antibody Reactions

KW - Betacoronavirus/immunology

KW - Binding Sites

KW - COVID-19

KW - Coronavirus Infections/drug therapy

KW - Cricetinae

KW - Crystallography, X-Ray

KW - Disease Models, Animal

KW - Humans

KW - Kinetics

KW - Lung/immunology

KW - Mice

KW - Mice, Inbred C57BL

KW - Molecular Dynamics Simulation

KW - Pandemics

KW - Peptidyl-Dipeptidase A/chemistry

KW - Pneumonia, Viral/drug therapy

KW - Protein Binding

KW - SARS-CoV-2

KW - Spike Glycoprotein, Coronavirus/chemistry

U2 - 10.1016/j.cell.2020.09.049

DO - 10.1016/j.cell.2020.09.049

M3 - SCORING: Journal article

C2 - 33058755

VL - 183

SP - 1058-1069.e19

JO - CELL

JF - CELL

SN - 0092-8674

IS - 4

ER -