Humanized monoclonal antibody against West Nile virus envelope protein administered after neuronal infection protects against lethal encephalitis in hamsters

Humanized monoclonal antibody against West Nile virus envelope protein administered after neuronal infection protects against lethal encephalitis in hamsters
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DOI:
10.1086/508293
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发表时间:
2006-11-01
影响因子:
6.4
通讯作者:
Diamond, Michael S.
Diamond, Michael S.
中科院分区:
医学2区
文献类型:
--
作者:
Morrey, John D.;Siddharthan, Venkatraman;Diamond, Michael S.

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感染西尼罗病毒(WNV)的人在临床上可能出现提示神经系统感染的症状。在动物模型中,几乎所有西尼罗河病毒疾病的治疗方法只有在病毒攻击之前或之后不久才有效。在这里,我们评估了一种有效的中和性抗西尼罗河病毒人源化单克隆抗体(MAb) hE16,是否可以在病毒感染大脑神经元后改善仓鼠模型的病程。注射病毒5 d后,采用细胞病理学、定量逆转录聚合酶链反应、免疫组化染色等方法检测鼠脑内西尼罗河病毒。值得注意的是,通过腹腔注射hE16病毒治疗5天后,80%-90%的仓鼠存活,而安慰剂治疗仓鼠的存活率为37% (P
Humans infected with West Nile virus (WNV) may clinically present with symptoms that are suggestive of neurological infection. Nearly all treatments of WNV disease have been effective in animal models only if administered before or soon after viral challenge. Here, we evaluated whether a potent neutralizing anti-WNV humanized monoclonal antibody (MAb), hE16, could improve the course of disease in a hamster model when administered after the virus had infected neurons in the brain. Five days after viral injection, WNV was detected in the brains of hamsters by cytopathic assay, quantitative reverse-transcription polymerase chain reaction, and immunohistochemical staining of WNV envelope in neurons. Notably, 80%-90% of the hamsters treated 5 days after viral injection by intraperitoneal injection with hE16 survived the disease, compared with 37% of the placebo-treated hamsters (P