作者: Richter, Anja ; Bertzbach, Luca D ; Dietert, Kristina ; Hoffmann, Julius ; Wilson, Ian A ; Homeyer, Marie A ; Jeworowski, Lara Maria ; Sander, Leif E ; Gruber, Achim D ; Schwarz, Tatjana ; van Hoof, Scott ; Suttorp, Norbert ; Skriner, Karl ; Corman, Victor Max ; Liu, Hejun ; Stöffler, Laura ; Yuan, Meng ; Barthel, Paula Charlotte ; Kurth, Florian ; Li, Lucie Y ; Hocke, Andreas C ; Endres, Matthias ; Schmitz, Dietmar ; von Wardenburg, Niels ; Abdelgawad, Azza ; Schmidt, Marie Luisa ; Wu, Nicholas C ; Trimpert, Jakob ; Reincke, S Momsen ; Vladimirova, Daria ; Witzenrath, Martin ; Osterrieder, Nikolaus ; Prüss, Harald ; Kreye, Jakob ; Müller, Marcel Alexander ; Hippenstiel, Stefan ; Drosten, Christian ; Höltje, Markus ; Zhu, Xueyong ; Sánchez-Sendin, Elisa ; Kornau, Hans-Christian ; Wendisch, Daniel ; Franke, Christiana ; Lee, Chang-Chun D

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.

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

作者: Hippenstiel, Stefan ; Wilson, Ian A ; Zhu, Xueyong ; Yuan, Meng ; Sander, Leif E ; Schwarz, Tatjana ; Sánchez-Sendin, Elisa ; Homeyer, Marie A ; Endres, Matthias ; Max Corman, Victor ; von Wardenburg, Niels ; Hoffmann, Julius ; Skriner, Karl ; Trimpert, Jakob ; Witzenrath, Martin ; Wendisch, Daniel ; Barthel, Paula Charlotte ; Hocke, Andreas C ; Stöffler, Laura ; Osterrieder, Nikolaus ; Suttorp, Norbert ; Franke, Christiana ; Richter, Anja ; Abdelgawad, Azza ; Vladimirova, Daria ; Drosten, Christian ; Schmitz, Dietmar ; van Hoof, Scott ; Li, Lucie Y ; Höltje, Markus ; Reincke, S Momsen ; Jeworowski, Lara Maria ; Lee, Chang-Chun D ; Dietert, Kristina ; Wu, Nicholas C ; Müller, Marcel Alexander ; Kreye, Jakob ; Schmidt, Marie Luisa ; Liu, Hejun ; Gruber, Achim D ; Prüss, Harald ; Kornau, Hans-Christian ; Kurth, Florian ; Bertzbach, Luca D

ABSTRACTThe 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 IC50of 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.

Viruses3区 · 医学

Aptamer BC 007’s Affinity to Specific and Less-Specific Anti-SARS-CoV-2 Neutralizing Antibodies

3区 · 医学

ArticleOA

作者: Göttel, Peter ; Haberland, Annekathrin ; Nikolenko, Heike ; Dallmann, Andre ; Weisshoff, Hardy ; Müller, Johannes ; Krylova, Oxana

COVID-19 is a pandemic respiratory disease that is caused by the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Anti-SARS-CoV-2 antibodies are essential weapons that a patient with COVID-19 has to combat the disease. When now repurposing a drug, namely an aptamer that interacts with SARS-CoV-2 proteins for COVID-19 treatment (BC 007), which is, however, a neutralizer of pathogenic autoantibodies in its original indication, the possibility of also binding and neutralizing anti-SARS-CoV-2 antibodies must be considered. Here, the highly specific virus-neutralizing antibodies have to be distinguished from the ones that also show cross-reactivity to tissues. The last-mentioned could be the origin of the widely reported SARS-CoV-2-induced autoimmunity, which should also become a target of therapy. We, therefore, used enzyme-linked immunosorbent assay (ELISA) technology to assess the binding of well-characterized publicly accessible anti-SARS-CoV-2 antibodies (CV07-209 and CV07-270) with BC 007. Nuclear magnetic resonance spectroscopy, isothermal calorimetric titration, and circular dichroism spectroscopy were additionally used to test the binding of BC 007 to DNA-binding sequence segments of these antibodies. BC 007 did not bind to the highly specific neutralizing anti-SARS-CoV-2 antibody but did bind to the less specific one. This, however, was a lot less compared to an autoantibody of its original indication (14.2%, range 11.0–21.5%). It was also interesting to see that the less-specific anti-SARS-CoV-2 antibody also showed a high background signal in the ELISA (binding on NeutrAvidin-coated or activated but noncoated plastic plate). These initial experiments suggest that the risk of binding and neutralizing highly specific anti-SARS CoV-2 antibodies by BC 007 should be low.

100 项与 CV07-209 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
新型冠状病毒感染	临床前	德国	Charité - Universitätsmedizin Berlin	-
新型冠状病毒感染	临床前	德国	German Center for Neurodegenerative Diseases	-
新型冠状病毒感染	临床前	德国	Miltenyi GmbH	-