A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model

Kreye, J.; Reincke, S. M.; Kornau, H.-C.; Sanchez-Sendin, E.; Corman, V. M.; Liu, H.; Yuan, M.; Wu, N. C.; Zhu, X.; Lee, C.-C. D.; Trimpert, J.; Hoeltje, M.; Dietert, K.; Stoeffler, L.; von Wardenburg, N.; van Hoof, S.; Homeyer, M. A.; Hoffmann, J.; Abdelgawad, A.; Gruber, A. D.; Bertzbach, L. D.; Vladimirova, D.; Li, L. Y.; Barthel, P. C.; Skriner, K.; Hocke, A. C.; Hippenstiel, S.; Witzenrath, M.; Suttorp, N.; Kurth, F.; Franke, C.; Endres, M.; Schmitz, D.; Jeworowski, L. M.; Richter, A.; Schmidt, M. L.; Schwarz, T.; Mueller, M. A.; Drosten, C.; Wendisch, D.; Sander, L. E.; Osterrieder, N.

doi:10.1101/2020.08.15.252320

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bioRxiv · 10.1101/2020.08.15.252320

A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model

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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 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 [A] 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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Kreye, J., Reincke, S. M., Kornau, H.-C., Sanchez-Sendin, E., Corman, V. M., Liu, H., Yuan, M., Wu, N. C., Zhu, X., Lee, C.-C. D., Trimpert, J., Hoeltje, M., Dietert, K., Stoeffler, L., von Wardenburg, N., van Hoof, S., Homeyer, M. A., Hoffmann, J., Abdelgawad, A., Gruber, A. D., Bertzbach, L. D., Vladimirova, D., Li, L. Y., Barthel, P. C., Skriner, K., Hocke, A. C., Hippenstiel, S., Witzenrath, M., Suttorp, N., Kurth, F., Franke, C., Endres, M., Schmitz, D., Jeworowski, L. M., Richter, A., Schmidt, M. L., Schwarz, T., Mueller, M. A., Drosten, C., Wendisch, D., Sander, L. E., Osterrieder, N.. 2020-08-16. A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model. https://doi.org/10.1101/2020.08.15.252320

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