Characterization of neutralizing antibody with prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus monkeys.
Characterization of neutralizing antibody with prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus monkeys.
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DOI：
10.1038/s41467-020-19568-1
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发表时间：
2020-11-13
影响因子：
16.6
通讯作者：
Liu D
中科院分区：
文献类型：
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作者：
Wang S;Peng Y;Wang R;Jiao S;Wang M;Huang W;Shan C;Jiang W;Li Z;Gu C;Chen B;Hu X;Yao Y;Min J;Zhang H;Chen Y;Gao G;Tang P;Li G;Wang A;Wang L;Zhang J;Chen S;Gui X;Yuan Z;Liu D
治疗COVID-19迫切需要有效的干预措施。在这里，我们报告了一个单克隆抗体（mAb），MW 05，具有中和活性，通过破坏受体结合域（RBD）与血管紧张素转换酶2（ACE 2）受体的相互作用。Fc与FcγRIIB的交联介导MW 05的抗体依赖性增强（ADE）活性。通过将LALA突变引入Fc区（MW 05/LALA）消除该活性。在恒河猴中观察到对SARS-CoV-2的有效预防和治疗作用。单剂量MW 05/LALA在预防性治疗中阻断SARS-CoV-2感染，在治疗性治疗环境中在三天内清除SARS-CoV-2。这些结果为开发MW 05/LALA作为COVID-19的抗病毒策略铺平了道路。在本文中，作者描述了一种来自COVID-19恢复期患者的单克隆抗体，该抗体干扰SARS-CoV-2与ACE 2的刺突结合，并在非人灵长类动物中具有预防和治疗活性。通过突变抗体的Fc区来防止感染的抗体依赖性增强。
Efficacious interventions are urgently needed for the treatment of COVID-19. Here, we report a monoclonal antibody (mAb), MW05, with SARS-CoV-2 neutralizing activity by disrupting the interaction of receptor binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2) receptor. Crosslinking of Fc with FcγRIIB mediates antibody-dependent enhancement (ADE) activity by MW05. This activity is eliminated by introducing the LALA mutation to the Fc region (MW05/LALA). Potent prophylactic and therapeutic effects against SARS-CoV-2 are observed in rhesus monkeys. A single dose of MW05/LALA blocks infection of SARS-CoV-2 in prophylactic treatment and clears SARS-CoV-2 in three days in a therapeutic treatment setting. These results pave the way for the development of MW05/LALA as an antiviral strategy for COVID-19. Here the authors characterize a monoclonal antibody from a COVID-19 convalescent patient that interferes with SARS-CoV-2 spike binding to ACE2 and has prophylactic and therapeutic activity in non-human primates. Antibody-dependent enhancement of infection is prevented by mutating the Fc region of the antibody.
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Chadox1 NCOV-19疫苗可防止恒河猕猴中的SARS-COV-2肺炎。
影响因子：
64.8
作者：
van Doremalen N;Lambe T;Spencer A;Belij-Rammerstorfer S;Purushotham JN;Port JR;Avanzato VA;Bushmaker T;Flaxman A;Ulaszewska M;Feldmann F;Allen ER;Sharpe H;Schulz J;Holbrook M;Okumura A;Meade-White K;Pérez-Pérez L;Edwards NJ;Wright D;Bissett C;Gilbride C;Williamson BN;Rosenke R;Long D;Ishwarbhai A;Kailath R;Rose L;Morris S;Powers C;Lovaglio J;Hanley PW;Scott D;Saturday G;de Wit E;Gilbert SC;Munster VJ
通讯作者：
Munster VJ
影响因子：
7.6
作者：
Wang Q;Wong G;Lu G;Yan J;Gao GF
通讯作者：
Gao GF
影响因子：
5.4
作者：
Jaume, Martial;Yip, Ming S.;Peiris, J. S. Malik
通讯作者：
Peiris, J. S. Malik
DOI：
10.1016/s0140-6736(04)16506-9
发表时间：
2004-06-26
期刊：
Lancet (London, England)
影响因子：
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作者：
ter Meulen J;Bakker AB;van den Brink EN;Weverling GJ;Martina BE;Haagmans BL;Kuiken T;de Kruif J;Preiser W;Spaan W;Gelderblom HR;Goudsmit J;Osterhaus AD
通讯作者：
Osterhaus AD
DOI：
10.1038/nrmicro2090
发表时间：
2009-03
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
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