Therapeutic treatment of Nipah virus infection in nonhuman primates with a neutralizing human monoclonal antibody.
Therapeutic treatment of Nipah virus infection in nonhuman primates with a neutralizing human monoclonal antibody.
复制标题
DOI：
10.1126/scitranslmed.3008929
复制
发表时间：
2014-06-25
影响因子：
17.1
通讯作者：
Broder CC
中科院分区：
文献类型：
--
作者：
Geisbert TW;Mire CE;Geisbert JB;Chan YP;Agans KN;Feldmann F;Fenton KA;Zhu Z;Dimitrov DS;Scott DP;Bossart KN;Feldmann H;Broder CC
尼帕病毒（NiV）是一种新出现的人畜共患副粘病毒，可引起猪和人类严重且往往致命的疾病。目前还没有批准用于人类的疫苗或治疗方法。在NiV感染的小动物模型中的研究表明，抗体治疗可能是一种有前途的治疗方法。然而，大多数研究都是在病毒暴露后不久动物出现疾病迹象之前评估治疗。我们在病毒暴露后的几个时间点评估了全人单克隆抗体m102.4的疗效，包括在NiV病的均匀致死性非人灵长类动物模型中临床疾病的发作。用致死剂量的NiV对16只非洲绿色猴（AGM）进行肠道内攻击，并在病毒攻击后1、3或5天开始向12只动物输注m102.4（15 mg/kg）两次，约2天后再次输注。病毒RNA、感染性病毒和/或NiV特异性免疫应答的存在证明所有受试者在攻毒后均被感染。所有12个接受m102.4的AGM在感染后存活，而未接受治疗的对照受试者在感染后8至10天死于疾病。第5天治疗组中的AGM表现出疾病的临床体征，但所有动物在第16天恢复。这些结果代表了研究药物在非人灵长类动物中对NiV的成功体内治疗疗效，并强调了单克隆抗体对高致病性人畜共患病的潜在影响。
Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes severe and often fatal disease in pigs and humans. There are currently no vaccines or treatments approved for human use. Studies in small-animal models of NiV infection suggest that antibody therapy may be a promising treatment. However, most studies have assessed treatment at times shortly after virus exposure before animals show signs of disease. We assessed the efficacy of a fully human monoclonal antibody, m102.4, at several time points after virus exposure including at the onset of clinical illness in a uniformly lethal nonhuman primate model of NiV disease. Sixteen African green monkeys (AGMs) were challenged intratracheally with a lethal dose of NiV, and 12 animals were infused twice with m102.4 (15 mg/kg) beginning at either 1, 3, or 5 days after virus challenge and again about 2 days later. The presence of viral RNA, infectious virus, and/or NiV-specific immune responses demonstrated that all subjects were infected after challenge. All 12 AGMs that received m102.4 survived infection, whereas the untreated control subjects succumbed to disease between days 8 and 10 after infection. AGMs in the day 5 treatment group exhibited clinical signs of disease, but all animals recovered by day 16. These results represent the successful therapeutic in vivo efficacy by an investigational drug against NiV in a nonhuman primate and highlight the potential impact that a monoclonal antibody can have on a highly pathogenic zoonotic human disease.
登录
查看更多内容
影响因子：
3.7
作者：
Geisbert, Thomas W.;Daddario-DiCaprio, Kathleen M.;Broder, Christopher C.
通讯作者：
Broder, Christopher C.
影响因子：
6.4
作者：
Zhu, Zhongyu;Bossart, Katharine N.;Dimitrov, Dimiter S.
通讯作者：
Dimitrov, Dimiter S.
影响因子：
--
作者：
Geisbert TW;Feldmann H;Broder CC
通讯作者：
Broder CC
影响因子：
17.1
作者：
Bossart KN;Geisbert TW;Feldmann H;Zhu Z;Feldmann F;Geisbert JB;Yan L;Feng YR;Brining D;Scott D;Wang Y;Dimitrov AS;Callison J;Chan YP;Hickey AC;Dimitrov DS;Broder CC;Rockx B
通讯作者：
Rockx B
影响因子：
5.4
作者：
Guillaume, V;Contamin, H;Wild, TF
通讯作者：
Wild, TF