Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike

Liu Lihong; Wang Pengfei; Nair Manoj S.; Yu Jian; Rapp Micah; Wang Qian; Luo Yang; Chan Jasper F. -W.; Sahi Vincent; Figueroa Amir; Guo Xinzheng V.; Cerutti Gabriele; Bimela Jude; Gorman Jason; Zhou Tongqing; Chen Zhiwei; Yuen Kwok-Yung; Kwong Peter D.; Sodroski Joseph G.; Yin Michael T.; Sheng Zizhang; Huang Yaoxing; Shapiro Lawrence; Ho David D.

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Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike

机译：在SARS-COV-2穗上对多个表位的有效中和抗体

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The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continues, with devasting consequences for human lives and the global economy(1,2). The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this coronavirus. Here we report the isolation of sixty-one SARS-CoV-2-neutralizing monoclonal antibodies from five patients infected with SARS-CoV-2 and admitted to hospital with severe coronavirus disease 2019 (COVID-19). Among these are nineteen antibodies that potently neutralized authentic SARS-CoV-2 in vitro, nine of which exhibited very high potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng ml(-1). Epitope mapping showed that this collection of nineteen antibodies was about equally divided between those directed against the receptor-binding domain (RBD) and those directed against the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody that targets the RBD, a second that targets the NTD, and a third that bridges two separate RBDs showed that the antibodies recognize the closed, 'all RBD-down' conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.

机译：严重的急性呼吸综合征冠状病毒-2（SARS-COV-2）大流行持续，对人类生活和全球经济的破坏后果（1,2）。病毒中和单克隆抗体的发现和开发可以是治疗或预防该冠状病毒感染的一种方法。在这里，我们报告了来自感染SARS-COV-2的五名患者的六十六个SARS-COV-2中和单克隆抗体的分离，并参加了2019年严重冠状病毒疾病的医院（Covid-19）。其中包括十九六个抗体，其在体外具有纯粹的典型的SARS-COV-2，其中九个具有非常高的效力，病毒抑制浓度为0.7至9ng mL（-1）。表位映射表明，该收集在含有对受体结合结构域（RBD）的那些之间的那些近似分裂，指向含有N-末端结构域（NTD）的那些，表明病毒顶部的这些区域都是两种区域穗是免疫原性的。此外，另外两种强大的中和抗体认可的季齿性表位与尖峰顶部的域重叠。靶向RBD的一抗的冷冻电子显微镜重建，靶向NTD的一秒钟，以及桥接两个单独的RBD的第三个抗体表明抗体识别封闭，“所有RBD-unply”的峰值构象。这些单克隆抗体中的几种是临床开发的候选者，作为针对SARS-COV-2的潜在治疗和/或预防剂。

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《Nature》 |2020年第7821期|450-456|共7页
作者
Liu Lihong; Wang Pengfei; Nair Manoj S.; Yu Jian; Rapp Micah; Wang Qian; Luo Yang; Chan Jasper F. -W.; Sahi Vincent; Figueroa Amir; Guo Xinzheng V.; Cerutti Gabriele; Bimela Jude; Gorman Jason; Zhou Tongqing; Chen Zhiwei; Yuen Kwok-Yung; Kwong Peter D.; Sodroski Joseph G.; Yin Michael T.; Sheng Zizhang; Huang Yaoxing; Shapiro Lawrence; Ho David D.;
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作者单位

Columbia Univ Vagelos Coll Phys & Surg Aaron Diamond AIDS Res Ctr New York NY 10027 USA;

Columbia Univ Vagelos Coll Phys & Surg Aaron Diamond AIDS Res Ctr New York NY 10027 USA;

Columbia Univ Vagelos Coll Phys & Surg Aaron Diamond AIDS Res Ctr New York NY 10027 USA;

Columbia Univ Vagelos Coll Phys & Surg Aaron Diamond AIDS Res Ctr New York NY 10027 USA;

Columbia Univ Zuckerman Mind Brain Behav Inst New York NY 10027 USA;

Harvard Med Sch Dana Farber Canc Inst Boston MA 02115 USA;

Columbia Univ Vagelos Coll Phys & Surg Aaron Diamond AIDS Res Ctr New York NY 10027 USA;

Univ Hong Kong Li Ka Shing Fac Med Dept Microbiol State Key Lab Emerging Infect Dis Carol Yu Ctr In Hong Kong Peoples R China|Univ Hong Kong Health InnoHK Ctr Virol Vaccinol & Therapeut Hong Kong Peoples R China;

Columbia Univ Vagelos Coll Phys & Surg Aaron Diamond AIDS Res Ctr New York NY 10027 USA;

Columbia Univ Vagelos Coll Phys & Surg Dept Microbiol & Immunol Flow Cytometry Core New York NY USA;

Columbia Univ Vagelos Coll Phys & Surg Human Immune Monitoring Core New York NY USA;

NIH Vaccine Res Ctr Bldg 10 Bethesda MD 20892 USA;

NIH Vaccine Res Ctr Bldg 10 Bethesda MD 20892 USA;

Univ Hong Kong Li Ka Shing Fac Med Dept Microbiol State Key Lab Emerging Infect Dis Carol Yu Ctr In Hong Kong Peoples R China|Univ Hong Kong Health InnoHK Ctr Virol Vaccinol & Therapeut Hong Kong Peoples R China|Univ Hong Kong Li Ka Shing Fac Med AIDS Inst Hong Kong Peoples R China;

Univ Hong Kong Li Ka Shing Fac Med Dept Microbiol State Key Lab Emerging Infect Dis Carol Yu Ctr In Hong Kong Peoples R China;

Columbia Univ Dept Biochem New York NY 10027 USA;

Columbia Univ Vagelos Coll Phys & Surg Dept Internal Med Div Infect Dis New York NY USA;

Columbia Univ Vagelos Coll Phys & Surg Aaron Diamond AIDS Res Ctr New York NY 10027 USA|Columbia Univ Zuckerman Mind Brain Behav Inst New York NY 10027 USA;

Columbia Univ Vagelos Coll Phys & Surg Aaron Diamond AIDS Res Ctr New York NY 10027 USA;

Columbia Univ Vagelos Coll Phys & Surg Aaron Diamond AIDS Res Ctr New York NY 10027 USA|Columbia Univ Zuckerman Mind Brain Behav Inst New York NY 10027 USA|Columbia Univ Dept Biochem New York NY 10027 USA;

Columbia Univ Vagelos Coll Phys & Surg Aaron Diamond AIDS Res Ctr New York NY 10027 USA;

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收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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1. Receptor-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus Spike Protein Contains Multiple Conformation-Dependent Epitopes that Induce Highly Potent Neutralizing Antibodies. [J] . He Y, Lu H, Siddiqui P, The Journal of Immunology: Official Journal of the American Association of Immunologists . 2005,第8期

机译：严重急性呼吸系统综合症冠状病毒突突蛋白的受体结合域包含多个构象依赖性表位，可诱导高强度中和抗体。
2. Receptor-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus Spike Protein Contains Multiple Conformation-Dependent Epitopes that Induce Highly Potent Neutralizing Antibodies [J] . Yuxian He, Hong Lu, Pamela Siddiqui, The journal of immunology . 2005,第8期

机译：严重急性呼吸系统综合症冠状病毒穗蛋白的受体结合域包含多个构象依赖性抗原决定簇，可诱导高度有效的中和抗体。
3. Receptor-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus Spike Protein Contains Multiple Conformation-Dependent Epitopes that Induce Highly Potent Neutralizing Antibodies [J] . Yuxian He, Hong Lu, Pamela Siddiqui, The journal of immunology . 2005,第8期

机译：严重急性呼吸系统综合症冠状病毒穗蛋白的受体结合域包含多个构象依赖性抗原决定簇，可诱导高度有效的中和抗体。
4. Generation of Potent Mouse Monoclonal Antibodies to Self-Proteins Using T-Cell Epitope "Tags" [C] . Jennifer L. Percival-Alwyn, Elizabeth Engl, Benjamin Kemp, PEGS . 2014

机译：使用T细胞表位“标签”产生效率小鼠单克隆抗体对自我蛋白质“标签”
5. The potently neutralizing monoclonal antibody 1B7: Its unique epitope, effects on intracellular trafficking, and elicitation upon infection with pertussis. [D] . Sutherland, Jamie Nicole. 2010

机译：强效中和性单克隆抗体1B7：其独特的表位，对细胞内运输有影响，并在感染百日咳后诱发。
6. Bispecific VH/Fab antibodies targeting neutralizing and non-neutralizing Spike epitopes demonstrate enhanced potency against SARS-CoV-2 [O] . Shion A. Lim, Josef A. Gramespacher, Katarina Pance, 2021

机译：靶向中和和非中和尖峰表征的双特异性VH / FAB抗体表现出对SARS-COV-2的增强效力
7. Potent neutralizing antibodies in the sera of convalescent COVID-19 patients are directed against conserved linear epitopes on the SARS-CoV-2 spike protein [O] . Chek Meng Poh, Guillaume Carissimo, Bei Wang, 2020

机译：康复Covid-19患者血清中的有效的中和抗体是针对SARS-COV-2穗蛋白的保守线性表位

Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike

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