A neutralizing human monoclonal antibody protects african green monkeys from hendra virus challenge.
A neutralizing human monoclonal antibody protects african green monkeys from hendra virus challenge.
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DOI：
10.1126/scitranslmed.3002901
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发表时间：
2011-10-19
影响因子：
17.1
通讯作者：
Rockx B
中科院分区：
文献类型：
--
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
亨德拉病毒(HEV)是一种新近出现的人畜共患副粘病毒，可在马和人身上引起严重的、往往是致命的疾病。HEV被归类为生物安全4级制剂，这使得动物模型的开发和潜在疗法和疫苗的测试具有挑战性。最近发现非洲绿猴(AGM)感染HEV，该病反映了人类致命的HEV感染，表现为多系统血管炎，病毒在血管组织中广泛复制，肺、脾和脑出现严重的病理表现。在这里，我们证明了m102.4，一种有效的HEV中和人类单抗(HmAb)，可以保护AGM免受感染后疾病(P.I.)的影响。用混合动力车。14名受试者气管内注射致死剂量的HEV，12名受试者从10小时、24小时或72小时开始两次输注100 mg剂量的m102.4。并在大约48小时后再次出现。病毒RNA、传染性病毒和HEV特异性免疫反应的存在表明，所有受试者在攻击后都被感染。接种m102.4的12个AGM全部存活；而未经治疗的对照组受试者在第8天P.I.死亡。72小时治疗组的动物表现出神经系统疾病的迹象，但所有动物在第16天P.I.开始恢复。这些结果代表了一种抗HEV的研究药物在体内暴露后的成功疗效，并突出了hmAb对人类疾病的潜在影响。
Hendra virus (HeV) is a recently emerged zoonotic paramyxovirus that can cause a severe and often fatal disease in horses and humans. HeV is categorized as a biosafety level 4 agent, which has made the development of animal models and testing of potential therapeutics and vaccines challenging. Infection of African Green monkeys (AGMs) with HeV was recently demonstrated and disease mirrored fatal HeV infection in humans, manifesting as a multisystemic vasculitis with widespread virus replication in vascular tissues and severe pathologic manifestations in the lung, spleen and brain. Here, we demonstrate that m102.4, a potent HeV neutralizing human monoclonal antibody (hmAb), can protect AGMs from disease post infection (p.i.) with HeV. Fourteen AGMs were challenged intratracheally with a lethal dose of HeV and twelve subjects were infused twice with a 100 mg dose of m102.4 beginning at either 10 hr, 24 hr or 72 hr p.i. and again approximately 48 hrs later. The presence of viral RNA, infectious virus and HeV-specific immune responses demonstrated that all subjects were infected following challenge. All twelve AGMs that received m102.4 survived infection; whereas the untreated control subjects succumbed to disease on day 8 p.i.. Animals in the 72 hr treatment group exhibited neurological signs of disease but all animals started to recover by day 16 p.i.. These results represent successful post-exposure in vivo efficacy by an investigational drug against HeV and highlight the potential impact a hmAb can have on human disease.
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影响因子：
11.8
作者：
Luby SP;Hossain MJ;Gurley ES;Ahmed BN;Banu S;Khan SU;Homaira N;Rota PA;Rollin PE;Comer JA;Kenah E;Ksiazek TG;Rahman M
通讯作者：
Rahman M
影响因子：
5.5
作者：
Pallister, Jackie;Middleton, Deborah;Wang, Lin-Fa;Klein, Reuben;Haining, Jessica;Robinson, Rachel;Yamada, Manabu;White, John;Payne, Jean;Feng, Yan-Ru;Chan, Yee-Peng;Broder, Christopher C.
通讯作者：
Broder, Christopher C.
影响因子：
5.4
作者：
Bishop, Kimberly A.;Stantchev, Tzanko S.;Broder, Christopher C.
通讯作者：
Broder, Christopher C.
影响因子：
11.4
作者：
Hanna, Jeffrey N.;McBride, William J.;Smith, Greg A.
通讯作者：
Smith, Greg A.
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.