Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection.
Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection.
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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。
DOI：
10.1016/j.antiviral.2016.06.003
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发表时间：
2016-08
影响因子：
7.6
通讯作者：
Zhou, Yusen
中科院分区：
文献类型：
--
作者：
Qiu, Hongjie;Sun, Shihui;Xiao, He;Feng, Jiannan;Guo, Yan;Tai, Wanbo;Wang, Yufei;Du, Lanying;Zhao, Guangyu;Zhou, Yusen
关键词：
中东呼吸综合征冠状病毒（MERS-CoV）正在持续传播，并在人类中引起严重和致命的急性呼吸道疾病。因此，迫切需要预防和治疗策略来控制MERS-CoV感染。在这里，我们产生了人源化单克隆抗体（mAb），命名为hMS-1，其以高亲和力靶向MERS-CoV受体结合结构域（RBD）。hMS-1显著阻断MERS-CoV RBD与其病毒受体人二肽基肽酶4（hDPP 4）的结合，有效中和原型MERS-CoV的感染，并通过识别高度保守的RBD表位有效交叉中和进化的MERS-CoV分离株。值得注意的是，用hMS-1的单剂量处理完全保护hDPP 4转基因（hDPP 4-Tg）小鼠免于MERS-CoV的致死感染。综上所述，我们的数据表明，hMS-1可能被开发为一种有效的免疫抑制剂，用于治疗MERS CoV感染的患者，特别是在紧急情况下。制备了抗中东呼吸综合征冠状病毒（MERS-CoV）的人源化单克隆抗体（mAb）hMS-1。hMS-1以高亲和力结合MERS-CoV受体结合结构域（RBD）。hMS-1通过阻断MERS-CoV RBD与hDPP 4受体的结合来中和MERS-CoV感染。人源化mAb hMS-1识别保守的RBD表位和交叉中和的MERS-CoV进化株。mAb hMS-1的单剂量治疗在hDPP 4-Tg小鼠模型中提供了免于致死MERS-CoV感染的完全保护。
Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases. A humanized monoclonal antibody (mAb) against Middle East respiratory syndrome coronavirus (MERS-CoV), hMS-1, was generated. hMS-1 bound to the MERS-CoV receptor binding domain (RBD) with high affinity. hMS-1 neutralized MERS-CoV infection by blocking the binding of MERS-CoV RBD to the hDPP4 receptor. Humanized mAb hMS-1 recognized conserved RBD epitopes and cross-neutralized MERS-CoV evolved strains. Single-dose treatment of mAb hMS-1 provided full protection from lethal MERS-CoV infection in an hDPP4-Tg mouse model.
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影响因子：
5.4
作者：
Gao, Jing;Lu, Guangwen;Gao, George F.
通讯作者：
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影响因子：
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影响因子：
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影响因子：
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通讯作者：
Du, Lanying