叙利亚仓鼠模型在气溶胶暴露于脑阿尔法病毒后并不反映类似人类的疾病

IF 2.3 Q3 BIOCHEMICAL RESEARCH METHODS
Christina L. Gardner, Rebecca A. Erwin-Cohen, Bridget S. Lewis, Russell R. Bakken, Shelley P. Honnold, Pamela J. Glass, Crystal W. Burke
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引用次数: 0

摘要

委内瑞拉马脑炎病毒(VEE)、东部马脑炎病毒(EEE)和西部马脑炎病毒(WEE)都是新世界α-病毒,它们会在马和人体内引起周期性的流行病暴发,可能导致严重的发病和死亡。目前,美国食品和药物管理局尚未批准使用疫苗或有效的抗病毒疗法。每年,人类感染脑炎阿尔巴病毒的病例数量有限;因此,疫苗或疗法的许可需要获得美国食品及药物管理局动物规则的批准。根据美国食品及药物管理局的动物规则进行审批,要求在动物模型中观察到的疾病能够再现在人类身上观察到的情况。目前,疫苗和疗法的初步测试是在小鼠模型中进行的。不幸的是,阿尔法病毒在小鼠中的疾病表现并不能忠实地再现人类疾病;VEEV 小鼠模型是致命的,而在人类中 VEEV 很少致命。为了确定一种更合适的小动物模型,我们对仓鼠进行了脑炎阿尔卑斯病毒感染气溶胶暴露模型的评估。在受感染的仓鼠身上观察到的病理变化、致死率和病毒血症与在 NHP 模型和人类身上观察到的不一致。这些数据表明,仓鼠不是测试疫苗或潜在抗病毒疗法的合适的脑炎α-病毒模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Syrian Hamsters Model Does Not Reflect Human-Like Disease after Aerosol Exposure to Encephalitic Alphaviruses
Venezuelan (VEE), eastern (EEE), and western (WEE) equine encephalitis viruses are encephalitic New World alphaviruses that cause periodic epizootic and epidemic outbreaks in horses and humans that may cause severe morbidity and mortality. Currently there are no FDA-licensed vaccines or effective antiviral therapies. Each year, there are a limited number of human cases of encephalitic alphaviruses; thus, licensure of a vaccine or therapeutic would require approval under the FDA animal rule. Approval under the FDA animal rule requires the disease observed in the animal model to recapitulate what is observed in humans. Currently, initial testing of vaccines and therapeutics is performed in the mouse model. Unfortunately, alphavirus disease manifestations in a mouse do not faithfully recapitulate human disease; the VEEV mouse model is lethal whereas in humans VEEV is rarely lethal. In an effort to identify a more appropriate small animal model, we evaluated hamsters in an aerosol exposure model of encephalitic alphavirus infection. The pathology, lethality, and viremia observed in the infected hamsters was inconsistent with what is observed in NHP models and humans. These data suggest that hamsters are not an appropriate model for encephalitic alphaviruses to test vaccines or potential antiviral therapies.
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来源期刊
Methods and Protocols
Methods and Protocols Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)
CiteScore
3.60
自引率
0.00%
发文量
85
审稿时长
8 weeks
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