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

被引:73
作者
Morrey, John D.
Siddharthan, Venkatraman
Olsen, Aaron L.
Roper, Grant Y.
Wang, Hong
Baldwin, Thomas J.
Koenig, Scott
Johnson, Syd
Nordstrom, Jeffrey L.
Diamond, Michael S.
机构
[1] Utah State Univ, Inst Antiviral Res, Dept Anim Dairy & Vet Sci, Logan, UT 84322 USA
[2] MacroGenics Inc, Rockville, MD USA
[3] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO USA
[4] Washington Univ, Sch Med, Dept Med, St Louis, MO USA
[5] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA
关键词
D O I
10.1086/508293
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 <= .001). The hamsters that received hE16 directly in the brain also exhibited markedly improved survival rates, compared with those in the placebo-treated hamsters. In prospective experiments, hamsters with high levels of infectious WNV in their cerebrospinal fluid were also protected by hE16 when administered 5 days after viral injection. These experiments suggest that humanized MAbs with potent neutralizing activity are a possible treatment for human patients after WNV has infected neurons in the central nervous system.
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收藏
页码:1300 / 1308
页数:9
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