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

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

doi:10.1016/j.cell.2020.09.049

Author(s)

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

Related Research Unit(s)

Detail(s)

Original language	English
Pages (from-to)	1058-1069
Journal / Publication	Cell
Volume	183
Issue number	4
Online published	23 Sep 2020
Publication status	Published - 12 Nov 2020

Link(s)

DOI	DOI https://doi.org/10.1016/j.cell.2020.09.049 Final Published version
	Check@CityULib
Link to Scopus	https://www.scopus.com/record/display.uri?eid=2-s2.0-85092092557&origin=recordpage
Permanent Link	https://scholars.cityu.edu.hk/en/publications/publication(912b931e-e7ec-49cc-bb86-6755835e01ea).html

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 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.

Research Area(s)

autoreactivity, COVID-19, crystal structures, hamster model, monoclonal antibody, neutralizing antibody, post-exposure, SARS-CoV-2, self-antigens, self-reactivity

Citation Format(s)

[ RIS ] [ BibTeX ]

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, Vol. 183, No. 4, 12.11.2020, p. 1058-1069.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62) › 21_Publication in refereed journal › peer-review

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, vol. 183, no. 4, pp. 1058-1069. https://doi.org/10.1016/j.cell.2020.09.049

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. https://doi.org/10.1016/j.cell.2020.09.049

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. https://doi.org/10.1016/j.cell.2020.09.049

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. / A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model. In: Cell. 2020 ; Vol. 183, No. 4. pp. 1058-1069.