Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
Vaccine. 2010 Dec 6;28(52):8315-26. doi: 10.1016/j.vaccine.2010.07.070. Epub 2010 Aug 3.
Historically, the safety of live attenuated vaccine candidates against neurotropic viruses was assessed by semi-quantitative analysis of virus-induced histopathology in the central nervous system of monkeys. We have developed a high-throughput automated image analysis (AIA) for the quantitative assessment of virus-induced neuroinflammation and neurodegeneration. Evaluation of the results generated by AIA showed that quantitative estimates of lymphocytic infiltration, microglial activation, and neurodegeneration strongly and significantly correlated with results of traditional histopathological scoring. In addition, we show that AIA is a targeted, objective, accurate, and time-efficient approach that provides reliable differentiation of virus neurovirulence. As such, it may become a useful tool in establishing consistent analytical standards across research and development laboratories and regulatory agencies, and may improve the safety evaluation of live virus vaccines. The implementation of this high-throughput AIA will markedly advance many fields of research including virology, neuroinflammation, neuroscience, and vaccinology.
从历史上看,通过对猴子中枢神经系统中病毒诱导的组织病理学的半定量分析来评估针对神经营养性病毒的减毒活疫苗候选物的安全性。我们已经开发了一种高通量自动化图像分析(AIA)方法,用于定量评估病毒引起的神经炎症和神经退行性变。对 AIA 生成的结果进行评估表明,淋巴细胞浸润、小胶质细胞激活和神经退行性变的定量估计与传统组织病理学评分的结果强烈且显著相关。此外,我们还表明,AIA 是一种靶向、客观、准确且高效的方法,可可靠地区分病毒的神经毒力。因此,它可能成为在研发实验室和监管机构中建立一致分析标准的有用工具,并可能改善活病毒疫苗的安全性评估。这种高通量 AIA 的实施将极大地推动病毒学、神经炎症、神经科学和疫苗学等多个领域的研究。