The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates.
The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates.
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DOI：
10.1126/scitranslmed.abf1906
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发表时间：
2021-05-12
影响因子：
17.1
通讯作者：
Falconer E
中科院分区：
文献类型：
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作者：
Jones BE;Brown-Augsburger PL;Corbett KS;Westendorf K;Davies J;Cujec TP;Wiethoff CM;Blackbourne JL;Heinz BA;Foster D;Higgs RE;Balasubramaniam D;Wang L;Zhang Y;Yang ES;Bidshahri R;Kraft L;Hwang Y;Žentelis S;Jepson KR;Goya R;Smith MA;Collins DW;Hinshaw SJ;Tycho SA;Pellacani D;Xiang P;Muthuraman K;Sobhanifar S;Piper MH;Triana FJ;Hendle J;Pustilnik A;Adams AC;Berens SJ;Baric RS;Martinez DR;Cross RW;Geisbert TW;Borisevich V;Abiona O;Belli HM;de Vries M;Mohamed A;Dittmann M;Samanovic MI;Mulligan MJ;Goldsmith JA;Hsieh CL;Johnson NV;Wrapp D;McLellan JS;Barnhart BC;Graham BS;Mascola JR;Hansen CL;Falconer E
LY-CoV555是一种SARS-CoV-2刺突蛋白特异性抗体，可中和SARS-CoV-2并保护非人灵长类动物的呼吸道免受感染。对于2019冠状病毒病（COVID-19）患者来说，最有希望的治疗选择是单克隆抗体（mab）。在这项研究中，Jones等人在体外和体内鉴定、表征并测试了一种这样的单抗LY-CoV555。他们发现LY-CoV555与严重急性呼吸窘迫综合征冠状病毒-2 （SARS-CoV-2）刺突蛋白结合，并阻止其与血管紧张素转换酶2的相互作用。用LY-CoV555进行预防性治疗可以保护非人类灵长类动物的上呼吸道和下呼吸道免受SARS-CoV-2感染。总之，这些数据支持LY-CoV555用于治疗COVID-19患者的临床应用。严重急性呼吸综合征冠状病毒-2 （SARS-CoV-2）构成公共卫生威胁，迫切需要预防和治疗药物。中和抗体是一类关键的治疗方法，它可以弥合广泛的疫苗接种运动，并为疫苗接种反应较差的人群提供治疗解决方案。在这里，我们报告了抗原特异性B细胞的高通量微流控筛选导致LY-CoV555（也称为bamlanivimab）的鉴定，这是一种有效的抗spike中和抗体，来自2019冠状病毒病（COVID-19）的住院康复期患者。对LY-CoV555的生化、结构和功能表征显示其与受体结合域具有高亲和力，抑制血管紧张素转换酶2的结合，并具有强中和活性。在食蟹猴中进行的LY-CoV555的药代动力学研究表明，其平均半衰期为13天，清除率为0.22 ml小时- 1 kg - 1，与典型的人类治疗性抗体一致。在恒河猴攻毒模型中，低至2.5 mg/kg的预防剂量可减少病毒接种后第6天收集的样本上呼吸道和下呼吸道的病毒复制。该抗体已进入临床测试，并正在针对包括预防和治疗在内的一系列COVID-19适应症进行评估。
LY-CoV555, a SARS-CoV-2 spike protein–specific antibody, neutralizes SARS-CoV-2 and protects the airways of nonhuman primates against infection. Among the most promising therapeutic options for individuals with coronavirus disease 2019 (COVID-19) are monoclonal antibodies (mAbs). In this study, Jones et al. identified, characterized, and tested one such mAb, LY-CoV555, in vitro and in vivo. They found that LY-CoV555 bound to the severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) spike protein and prevented its interaction with angiotensin-converting enzyme 2. Prophylactic treatment with LY-CoV555 protected the upper and lower respiratory tracts of nonhuman primates from becoming infected with SARS-CoV-2. Together, these data support the clinical use of LY-CoV555 for treating patients with COVID-19. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies are a key class of therapeutics that may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. Here, we report that high-throughput microfluidic screening of antigen-specific B cells led to the identification of LY-CoV555 (also known as bamlanivimab), a potent anti-spike neutralizing antibody from a hospitalized, convalescent patient with coronavirus disease 2019 (COVID-19). Biochemical, structural, and functional characterization of LY-CoV555 revealed high-affinity binding to the receptor-binding domain, angiotensin-converting enzyme 2 binding inhibition, and potent neutralizing activity. A pharmacokinetic study of LY-CoV555 conducted in cynomolgus monkeys demonstrated a mean half-life of 13 days and a clearance of 0.22 ml hour−1 kg−1, consistent with a typical human therapeutic antibody. In a rhesus macaque challenge model, prophylactic doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract in samples collected through study day 6 after viral inoculation. This antibody has entered clinical testing and is being evaluated across a spectrum of COVID-19 indications, including prevention and treatment.
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DOI：
10.1056/nejmoa2029849
发表时间：
2021-01-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Chen P;Nirula A;Heller B;Gottlieb RL;Boscia J;Morris J;Huhn G;Cardona J;Mocherla B;Stosor V;Shawa I;Adams AC;Van Naarden J;Custer KL;Shen L;Durante M;Oakley G;Schade AE;Sabo J;Patel DR;Klekotka P;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators
影响因子：
2.9
作者：
Barnard, Gavin C.;Hougland, Maria D.;Rajendra, Yashas
通讯作者：
Rajendra, Yashas
REGN-COV2抗体预防和治疗恒河猕猴和仓鼠中的SARS-COV-2感染。
DOI：
10.1126/science.abe2402
发表时间：
2020-11-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Baum A;Ajithdoss D;Copin R;Zhou A;Lanza K;Negron N;Ni M;Wei Y;Mohammadi K;Musser B;Atwal GS;Oyejide A;Goez-Gazi Y;Dutton J;Clemmons E;Staples HM;Bartley C;Klaffke B;Alfson K;Gazi M;Gonzalez O;Dick E Jr;Carrion R Jr;Pessaint L;Porto M;Cook A;Brown R;Ali V;Greenhouse J;Taylor T;Andersen H;Lewis MG;Stahl N;Murphy AJ;Yancopoulos GD;Kyratsous CA
通讯作者：
Kyratsous CA
DOI：
10.1107/s0907444909042073
发表时间：
2010-01
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Chen VB;Arendall WB 3rd;Headd JJ;Keedy DA;Immormino RM;Kapral GJ;Murray LW;Richardson JS;Richardson DC
通讯作者：
Richardson DC
影响因子：
2.7
作者：
Barnard, J;Rubin, DB
通讯作者：
Rubin, DB