Pilot Projects Component (Pilot Proj 2: Guccione)

地段项目2a。人类对天花反应的转录微阵列分析 预防针 在Relman实验室完成的这个项目的组成部分中，我们将使用cDNA 微阵列，以表征全球基因表达模式，在天花疫苗接种， 在批准的临床方案中登记的疫苗接种者的试点队列，以评估牛痘疫苗或 作为“第一反应者”接种疫苗。全球基因表达系统研究的价值 目前，该项目已在提供对正常细胞生理学和疾病的新见解方面得到了很好的建立 发病机制DNA微阵列提供了一种快速有效的方法来建立一个详细的基因图谱 表达程序潜在的生物过程，即使在没有良好的发达的先验 其行为的知识或模型。这些实验将使我们能够建立一个全面的图片， 人类对天花疫苗的反应的数千个基因。这些模式可以在以后 用于评估疫苗接种不良事件，并开发保护性疫苗的新替代标记物 不依赖于詹纳氏病变可视化的反应。虽然超出了这个范围 这些数据将创建一个框架，在其中比较保护性和非保护性 在非人灵长类动物天花模型中的疫苗应答，并从 人类数据使用来自用活天花病毒攻击的猴子的数据。我们长远的目标是 使用全基因组表达模式作为预测保护性疫苗反应的手段， 天花以及对疫苗不良反应。我们的具体 目标来自于这一背景和理由。

lot project 2a. Transcriptional microarray analysis of human responses to smallpox vaccination. In the component of this project to be done in the Relman laboratory, we will use cDNA microarrays to characterize global gene expression patterns in response to smallpox vaccination in a pilot cohort of vaccinees enrolled in approved clinical protocols to evaluate vaccinia vaccines or who are being vaccinated as 'first responders'. The value of systematic studies of global gene expression programs is now well established in providing new insights into normal cellular physiology and disease pathogenesis. DNA microarrays provide a rapid and efficient way to build a detailed map of the gene expression program underlying a biological process, even in the absence of well-developed prior knowledge or models of its behavior. These experiments will allow us to build a comprehensive picture, across thousands of genes, of the human response to smallpox vaccination. These patterns can later be used to assess adverse vaccination events, and develop new surrogate markers for a protective vaccine response that does not rely on visualization of a Jennerian lesion. Although beyond the scope of this proposal, these data will create a framework within which to compare protective and non-protective vaccine responses in a non-human primate model of smallpox, and derive patterns of protection from the human data using data from monkeys challenged with live smallpox virus. Our long-term objective is to use genome-wide expression patterns as a means of predicting protective vaccine responses against smallpox, as well as adverse.responses to vaccine, in humans early after immunization. Our Specific Aims follow from this background and rationale.