RT Journal Article
SR Electronic
T1 A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.15.252320
DO 10.1101/2020.08.15.252320
A1 Jakob Kreye
A1 S Momsen Reincke
A1 Hans-Christian Kornau
A1 Elisa Sánchez-Sendin
A1 Victor Max Corman
A1 Hejun Liu
A1 Meng Yuan
A1 Nicholas C. Wu
A1 Xueyong Zhu
A1 Chang-Chun D. Lee
A1 Jakob Trimpert
A1 Markus Höltje
A1 Kristina Dietert
A1 Laura Stöffler
A1 Niels von Wardenburg
A1 Scott van Hoof
A1 Marie A Homeyer
A1 Julius Hoffmann
A1 Azza Abdelgawad
A1 Achim D Gruber
A1 Luca D Bertzbach
A1 Daria Vladimirova
A1 Lucie Y Li
A1 Paula Charlotte Barthel
A1 Karl Skriner
A1 Andreas C Hocke
A1 Stefan Hippenstiel
A1 Martin Witzenrath
A1 Norbert Suttorp
A1 Florian Kurth
A1 Christiana Franke
A1 Matthias Endres
A1 Dietmar Schmitz
A1 Lara Maria Jeworowski
A1 Anja Richter
A1 Marie Luisa Schmidt
A1 Tatjana Schwarz
A1 Marcel Alexander Müller
A1 Christian Drosten
A1 Daniel Wendisch
A1 Leif E Sander
A1 Nikolaus Osterrieder
A1 Ian A Wilson
A1 Harald Prüss
YR 2020
UL http://biorxiv.org/content/early/2020/08/16/2020.08.15.252320.abstract
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 ten COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb CV07-209 neutralized authentic SARS-CoV-2 with IC50 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.Competing Interest StatementRelated to this work the German Center for Neurodegenerative Diseases (DZNE) and the Charite - Universitaetsmedizin have filed a patent application on which JK, SMR, HCK, ESS, VMC, MAM, DW, LES and HP are named as inventors.