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

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

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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

Detail(s)

Original languageEnglish
Pages (from-to)1058-1069
Journal / PublicationCell
Volume183
Issue number4
Online published23 Sep 2020
Publication statusPublished - 12 Nov 2020

Link(s)

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)

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 journalpeer-review

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