Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets.
Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets.
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DOI：
10.1016/j.antiviral.2018.06.006
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发表时间：
2018-08
影响因子：
7.6
通讯作者：
Feldmann H
中科院分区：
文献类型：
--
作者：
de Wit E;Feldmann F;Okumura A;Horne E;Haddock E;Saturday G;Scott D;Erlandson KJ;Stahl N;Lipsich L;Kyratsous CA;Feldmann H
确诊的中东呼吸综合征冠状病毒感染的高病死率凸显了迫切需要有效的治疗方法来降低疾病的严重程度和死亡率。 REGN3051 和 REGN3048 是两种针对 MERS-CoV 的全人源中和单克隆抗体 (mAb)，在预防性和治疗性治疗后，可减少表达人 DPP4 的小鼠中的病毒复制。在此，我们评估了 REGN3048 和 REGN3051 在普通狨猴感染 MERS-CoV 模型中的预防和治疗效果。静脉注射 mAb 可导致循环血液中出现高水平的 MERS-CoV 中和活性。当动物在攻击前一天接受 mAb 治疗时，呼吸道疾病的严重程度较轻，并且在同时接受 REGN3048 和 REGN3051 治疗的动物中，肺部的病毒载量减少。然而，攻击后第一天的治疗效果较差，因为它不能阻止严重呼吸道疾病的发展，并且所有接受治疗的动物都出现了与对照动物相似严重程度的支气管间质性肺炎。因此，mAb 施用在预防性治疗方案中可能比 MERS 的治疗更有效。 REGN3051 和 REGN3048 是两种人 MERS-CoV 中和单克隆抗体，可减少小鼠体内的病毒复制。我们评估了这些单克隆抗体在中东呼吸综合征冠状病毒感染的普通狨猴模型中的预防和治疗效果。 REGN3048 和 REGN3051 的预防性治疗可减轻严重的呼吸道疾病并减少病毒肺负荷。治疗效果较差，因为它不能阻止严重呼吸道疾病的发展。
The high case-fatality rate of confirmed MERS-CoV infections underlines the urgent need for an effective treatment to reduce the disease severity and mortality. REGN3051 and REGN3048 are two fully human neutralizing monoclonal antibodies (mAb) against MERS-CoV that reduced virus replication in mice expressing human DPP4 upon prophylactic and therapeutic treatment. Here, we evaluated the prophylactic and therapeutic efficacy of REGN3048 and REGN3051 in the common marmoset model of MERS-CoV infection. Intravenous administration of mAb resulted in high levels of MERS-CoV-neutralizing activity in circulating blood. When animals were treated with mAbs one day before challenge, respiratory disease was less severe and, in animals treated with both REGN3048 and REGN3051, viral loads in the lungs were reduced. However, therapeutic treatment on day one after challenge was less efficacious as it did not prevent the development of severe respiratory disease and all treated animals developed bronchointerstitial pneumonia of similar severity as the control animals. Thus, mAb administration may be more effective in a prophylactic treatment regimen rather than treatment of MERS. REGN3051 and REGN3048 are two human MERS-CoV-neutralizing monoclonal antibodies that reduced virus replication in mice. We evaluated the prophylactic and therapeutic efficacy of these mAbs in the common marmoset model of MERS-CoV infection. Prophylactic treatment with REGN3048 and REGN3051 resulted in less severe respiratory disease and reduced viral lung loads. Therapeutic treatment was less efficacious as it did not prevent the development of severe respiratory disease.
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使用人源化中和抗体进行单剂量治疗可以充分保护人类转基因小鼠模型免受致命的中东呼吸综合征（MERS）冠状病毒感染。
影响因子：
7.6
作者：
Qiu, Hongjie;Sun, Shihui;Xiao, He;Feng, Jiannan;Guo, Yan;Tai, Wanbo;Wang, Yufei;Du, Lanying;Zhao, Guangyu;Zhou, Yusen
通讯作者：
Zhou, Yusen
影响因子：
3.7
作者：
Johnson RF;Bagci U;Keith L;Tang X;Mollura DJ;Zeitlin L;Qin J;Huzella L;Bartos CJ;Bohorova N;Bohorov O;Goodman C;Kim DH;Paulty MH;Velasco J;Whaley KJ;Johnson JC;Pettitt J;Ork BL;Solomon J;Oberlander N;Zhu Q;Sun J;Holbrook MR;Olinger GG;Baric RS;Hensley LE;Jahrling PB;Marasco WA
通讯作者：
Marasco WA
影响因子：
7.6
作者：
van Doremalen N;Falzarano D;Ying T;de Wit E;Bushmaker T;Feldmann F;Okumura A;Wang Y;Scott DP;Hanley PW;Feldmann H;Dimitrov DS;Munster VJ
通讯作者：
Munster VJ
影响因子：
14.2
作者：
Hart, TK;Cook, RM;Herzyk, DJ
通讯作者：
Herzyk, DJ
影响因子：
6.7
作者：
Falzarano D;de Wit E;Feldmann F;Rasmussen AL;Okumura A;Peng X;Thomas MJ;van Doremalen N;Haddock E;Nagy L;LaCasse R;Liu T;Zhu J;McLellan JS;Scott DP;Katze MG;Feldmann H;Munster VJ
通讯作者：
Munster VJ