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

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 immu...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510528/
https://www.ncbi.nlm.nih.gov/pubmed/33058755
http://dx.doi.org/10.1016/j.cell.2020.09.049
Descripción
Sumario: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 IC(50) 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.

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