Rapid, non-invasive imaging of alphaviral brain infection: reducing animal numbers and morbidity to identify efficacy of potential vaccines and antivirals.
Rapid, non-invasive imaging of alphaviral brain infection: reducing animal numbers and morbidity to identify efficacy of potential vaccines and antivirals.
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DOI：
10.1016/j.vaccine.2011.09.130
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发表时间：
2011-11-21
期刊：
影响因子：
5.5
通讯作者：
Paessler, Slobodan
中科院分区：
文献类型：
--
作者：
Patterson, Michael;Poussard, Allison;Taylor, Katherine;Seregin, Alexey;Smith, Jeanon;Peng, Bi-Hung;Walker, Aida;Linde, Jenna;Smith, Jennifer;Salazar, Milagros;Paessler, Slobodan
快速准确地鉴定疾病进展是测试针对脑炎甲病毒的新型疫苗和抗病毒药的关键因素。典型的有效性研究使用大量动物和严重发病率或死亡率作为终点。新技术提供了一种减少和改进动物使用的方法，正如罗素和伯奇在休谟的3R（替代，减少，改进）中所提出的那样。体内成像系统（IVIS）和生物发光酶技术实现了动物需求的减少，同时缩短了实验时间并提高了定位活性病毒复制的准确性。在病毒性脑炎的小鼠模型中，中枢神经系统（CNS）病毒入侵发生迅速，但疾病发展相对缓慢，我们可视化了最初的脑感染，并增强了旨在预防脑感染的抗病毒药物或疫苗的有效性研究所需的数据收集过程。因此，我们通过鼻内接种转基因病原体，委内瑞拉马脑炎，表达荧光素酶基因感染小鼠。在这项研究中，我们能够在任何疾病临床体征出现前至少3天确定CNS的侵袭，从而降低动物发病率，为疾病和疫苗研究提供人道的手段，同时更准确和更快速地获得科学数据。基于我们从成像模型获得的数据，我们通过证明Ampligen（TLR-3激动剂）在预防CNS侵袭方面的功效，证实了该技术在临床前研究中的有用性。
Rapid and accurate identification of disease progression are key factors in testing novel vaccines and antivirals against encephalitic alphaviruses. Typical efficacy studies utilize a large number of animals and severe morbidity or mortality as an endpoint. New technologies provide a means to reduce and refine the animal use as proposed in Hume’s 3Rs (replacement, reduction, refinement) described by Russel and Burch. In vivo imaging systems (IVIS) and bioluminescent enzyme technologies accomplish the reduction of animal requirements while shortening the experimental time and improving the accuracy in localizing active virus replication. In the case of murine models of viral encephalitis in which central nervous system (CNS) viral invasion occurs rapidly but the disease development is relatively slow, we visualized the initial brain infection and enhance the data collection process required for efficacy studies on antivirals or vaccines that are aimed at preventing brain infection. Accordingly, we infected mice through intranasal inoculation with the genetically modified pathogen, Venezuelan equine encephalitis, which expresses a luciferase gene. In this study, we were able to identify the invasion of the CNS at least 3 days before any clinical signs of disease, allowing for reduction of animal morbidity providing a humane means of disease and vaccine research while obtaining scientific data accurately and more rapidly. Based on our data from the imaging model, we confirmed the usefulness of this technology in preclinical research by demonstrating the efficacy of Ampligen, a TLR-3 agonist, in preventing CNS invasion.
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影响因子：
3.6
作者：
Contag, CH;Contag, PR;Benaron, DA
通讯作者：
Benaron, DA
影响因子：
5.4
作者：
KINNEY, RM;CHANG, GJ;TRENT, DW
通讯作者：
TRENT, DW
影响因子：
5.4
作者：
Luker, GD;Prior, JL;Leib, DA
通讯作者：
Leib, DA
DOI：
10.1073/pnas.0711976105
发表时间：
2008-02-19
影响因子：
11.1
作者：
Trumpfheller, Christine;Caskey, Marina;Steinman, Ralph M.
通讯作者：
Steinman, Ralph M.
影响因子：
82.9
作者：
Contag, PR;Olomu, IN;Contag, CH
通讯作者：
Contag, CH