A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model.
A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model.
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DOI：
10.1016/j.cell.2020.09.049
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发表时间：
2020-11-12
期刊：
影响因子：
64.5
通讯作者：
Prüss H
中科院分区：
文献类型：
--
作者：
Kreye J;Reincke SM;Kornau HC;Sánchez-Sendin E;Corman VM;Liu H;Yuan M;Wu NC;Zhu X;Lee CD;Trimpert J;Höltje M;Dietert K;Stöffler L;von Wardenburg N;van Hoof S;Homeyer MA;Hoffmann J;Abdelgawad A;Gruber AD;Bertzbach LD;Vladimirova D;Li LY;Barthel PC;Skriner K;Hocke AC;Hippenstiel S;Witzenrath M;Suttorp N;Kurth F;Franke C;Endres M;Schmitz D;Jeworowski LM;Richter A;Schmidt ML;Schwarz T;Müller MA;Drosten C;Wendisch D;Sander LE;Osterrieder N;Wilson IA;Prüss H
SARS-CoV-2的出现导致了2019冠状病毒病（COVID-19）的大流行，表现为呼吸道症状和多器官功能障碍。需要详细描述病毒中和抗体和靶表位，以了解COVID-19的病理生理和指导免疫策略。在10例COVID-19患者的598种人单克隆抗体（mab）中，我们鉴定出40种强中和抗体。最有效的单抗CV07-209能中和真实的SARS-CoV-2， IC50值为3.1 ng/mL。在2.55和2.70 Å位点上与SARS-CoV-2受体结合域复合物的两种单克隆抗体的晶体结构揭示了ACE2附着的直接阻断。有趣的是，一些近种系的sars - cov -2中和单克隆抗体与哺乳动物自身抗原发生反应。CV07-209的预防和治疗应用保护仓鼠免受SARS-CoV-2感染，体重减轻和肺部病理。我们的研究结果表明，在SARS-CoV-2感染期间诱导非自我反应性病毒中和单抗是一种很有前途的治疗策略。一些SARS-CoV-2抗体与哺乳动物不同器官的自身抗原发生反应，两种抗体与SARS-CoV-2 RBD复合物的晶体结构在2.55/2.70 Å暴露后抗体治疗可保护受感染仓鼠的肺损伤。其中一些被发现在不同器官中与哺乳动物自身抗原表现出自身反应性。与SARS-CoV-2刺突RBD复合物的两种抗体的晶体结构从不同的接近角度揭示了抗体与ACE2结合位点的结合。进一步评估了一种抗体的体内功效，发现在仓鼠感染模型中既具有保护作用又有效。
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. Characterization of potent human monoclonal SARS-CoV-2-neutralizing antibodies Some SARS-CoV-2 antibodies reacted with mammalian self-antigens in different organs Crystal structures of two antibodies in complex with SARS-CoV-2 RBD at 2.55/2.70 Å Post-exposure antibody treatment protected from lung damage in infected hamsters Kreye et al. report isolation and characterization of monoclonal antibodies from COVID-19 patients, some of which were found to display autoreactivity with mammalian self-antigens in different organs. Crystal structures of two antibodies in complex with the SARS-CoV-2 spike RBD reveal antibody engagement with the ACE2 binding site from different approach angles. One antibody was evaluated further for in vivo efficacy and found to be both protective and efficacious post-challenge in a hamster infection model.
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影响因子：
3.7
作者：
Dietert K;Gutbier B;Wienhold SM;Reppe K;Jiang X;Yao L;Chaput C;Naujoks J;Brack M;Kupke A;Peteranderl C;Becker S;von Lachner C;Baal N;Slevogt H;Hocke AC;Witzenrath M;Opitz B;Herold S;Hackstein H;Sander LE;Suttorp N;Gruber AD
通讯作者：
Gruber AD
DOI：
10.1107/s0907444904019158
发表时间：
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影响因子：
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Schief WR
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