Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus
Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus
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DOI：
10.1073/pnas.1510199112
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发表时间：
2015-08-18
影响因子：
11.1
通讯作者：
Lanzavecchia, Antonio
中科院分区：
文献类型：
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作者：
Corti, Davide;Zhao, Jincun;Lanzavecchia, Antonio
中东呼吸综合症 (MERS) 是一种高度致命的肺部感染，由一种先前未识别的冠状病毒 (CoV) 引起，可能通过受感染的骆驼传播给人类。目前还没有针对 MERS 的许可疫苗或抗病毒药物，因此需要新的预防和治疗策略来对抗人类感染。在这项研究中，据我们所知，我们首次描述了从感染个体的记忆 B 细胞中分离出有效的 MERS-CoV 中和抗体。该抗体名为 LCA60，与刺突蛋白上的一个新位点结合，通过干扰与细胞受体 CD26 的结合，有效中和多种 MERS-CoV 分离株的感染。重要的是，使用表达人 CD26 的腺病毒转导并感染 MERS-CoV 的小鼠，我们表明 LCA60 在预防和暴露后环境中都能有效提供保护。该抗体可用于预防、高危个体的暴露后预防，或用于治疗中东呼吸综合征冠状病毒感染的人类病例。事实上，从对来自恢复期患者的 B 细胞进行初步筛选，到开发稳定的中国仓鼠卵巢 (CHO) 细胞系，产生超过 5 g/L 的中和抗体，仅用了 4 个月的时间，这一事实为针对新出现的病毒产生有效的抗病毒疗法提供了快速途径的一个例子。
Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a previously unidentified coronavirus (CoV), likely transmitted to humans by infected camels. There is no licensed vaccine or antiviral for MERS, therefore newprophylactic and therapeutic strategies to combat human infections are needed. In this study, we describe, for the first time, to our knowledge, the isolation of a potent MERS-CoV-neutralizing antibody from memory B cells of an infected individual. The antibody, named LCA60, binds to a novel site on the spike protein and potently neutralizes infection of multiple MERS-CoV isolates by interfering with the binding to the cellular receptor CD26. Importantly, using mice transduced with adenovirus expressing human CD26 and infected with MERS-CoV, we show that LCA60 can effectively protect in both prophylactic and postexposure settings. This antibody can be used for prophylaxis, for postexposure prophylaxis of individuals at risk, or for the treatment of human cases of MERS-CoV infection. The fact that it took only 4 mo from the initial screening of B cells derived from a convalescent patient for the development of a stable chinese hamster ovary (CHO) cell line producing neutralizing antibodies at more than 5 g/L provides an example of a rapid pathway toward the generation of effective antiviral therapies against emerging viruses.