Successful Treatment of Ebola Virus-Infected Cynomolgus Macaques with Monoclonal Antibodies
Successful Treatment of Ebola Virus-Infected Cynomolgus Macaques with Monoclonal Antibodies
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DOI：
10.1126/scitranslmed.3003876
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发表时间：
2012-06-13
影响因子：
17.1
通讯作者：
Kobinger, Gary P.
中科院分区：
文献类型：
--
作者：
Qiu, Xiangguo;Audet, Jonathan;Kobinger, Gary P.
埃博拉病毒（EBOV）被认为是最具侵略性的传染性病原体之一，能够在暴露后数天内导致人类和非人灵长类动物（NHP）死亡。最近的策略成功地预防了NHP在治疗后感染;然而，这些策略只有在感染前或感染后几分钟给予时才能成功。本工作显示，当在用EBOV致死性攻击后24小时开始间隔3天施用三个剂量时，针对埃博拉包膜糖蛋白（GP）的三种中和单克隆抗体（mAb）的组合导致完全存活（四只食蟹猴中的四只），而没有明显的副作用。在用EBOV致死攻击后48小时开始的相同处理导致四只食蟹猴中的两只完全恢复。存活者表现出EBOV-GP特异性体液和细胞介导的免疫应答。这些数据突出了抗体在体内控制EBOV复制的重要作用，并支持使用mAb对抗严重丝状病毒感染。
Ebola virus (EBOV) is considered one of the most aggressive infectious agents and is capable of causing death in humans and nonhuman primates (NHPs) within days of exposure. Recent strategies have succeeded in preventing acquisition of infection in NHPs after treatment; however, these strategies are only successful when administered before or minutes after infection. The present work shows that a combination of three neutralizing monoclonal antibodies (mAbs) directed against the Ebola envelope glycoprotein (GP) resulted in complete survival (four of four cynomolgus macaques) with no apparent side effects when three doses were administered 3 days apart beginning at 24 hours after a lethal challenge with EBOV. The same treatment initiated 48 hours after lethal challenge with EBOV resulted in two of four cynomolgus macaques fully recovering. The survivors demonstrated an EBOV-GP-specific humoral and cell-mediated immune response. These data highlight the important role of antibodies to control EBOV replication in vivo, and support the use of mAbs against a severe filovirus infection.