Publikationsdatenbank

A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model (2020)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Kreye, Jakob

Momsen Reincke, S.

Kornau, Hans-Christian

Sánchez-Sendin, Elisa

Corman, Victor Max

Liu, Hejun

Yuan, Meng

Wu, Nicholas C.

Zhu, Xueyong

Lee, Chang-Chun D.

Trimpert, Jakob (WE 5)

Höltje, Markus

Dietert, Kristina (WE 12)

Stöffler, Laura

von Wardenburg, Niels

van Hoof, Scott

Homeyer, Marie A.

Hoffmann, Julius

Abdelgawad, Azza (WE 5)

Gruber, Achim D. (WE 12)

Bertzbach, Luca D. (WE 5)

Vladimirova, Daria (WE 5)

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

Jeworoswski, Lara Maria

Richter, Anja

Schmidt, Marie Luisa

Schwarz, Tatjana

Müller, Marcel Alexander

Drosten, Christian

Wendisch, Daniel

Sander, Leif E.

Osterrieder, Nikolaus (WE 5)

Wilson, Ian A.

Prüss, Harald

Quelle

Cell

Bandzählung: 183

Heftzählung: 4

Seiten: 1058 – 1069.e19

ISSN: 0092-8674

Sprache

Englisch

Verweise

URL (Volltext): https://www.sciencedirect.com/science/article/pii/S0092867420312460

DOI: 10.1016/j.cell.2020.09.049

Pubmed: 33058755

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.