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. GruberLuca 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1058-1069.e19
JournalCell
Volume183
Issue number4
DOIs
StatePublished - Nov 12 2020

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model'. Together they form a unique fingerprint.

Cite this