Pilot Projects Component (Pilot Proj 2: Guccione)

Lot项目2a。人类对天花反应的转录微阵列分析 接种疫苗。 在瑞曼实验室完成的这个项目的组成部分中，我们将使用 用于表征天花疫苗接种后全球基因表达模式的微阵列 登记在经批准的临床方案中以评估牛痘疫苗的受试者队列或 作为“第一响应者”接种疫苗。全球基因表达系统研究的价值 现在，在提供对正常细胞生理学和疾病的新见解方面，计划已经建立得很好 发病机制。DNA微阵列提供了一种快速而有效的方法来构建详细的基因图谱 生物过程的基础表达程序，即使在没有发育良好的先前的情况下 关于它的行为的知识或模式。这些实验将使我们能够构建一幅全面的图景， 通过数千个基因，研究人类对天花疫苗的反应。这些模式可以在以后 用于评估不良疫苗接种事件，并为保护性疫苗开发新的替代标记 这种反应不依赖于Jennerian病变的可视化。虽然超出了本文的范围 提议，这些数据将创建一个框架，在其中比较保护性和非保护性 疫苗在非人类灵长类动物天花模型中的反应，并从 人类数据使用来自猴子的数据，这些数据来自于受到活天花病毒挑战的猴子。我们的长期目标是 使用全基因组表达模式作为预测保护性疫苗反应的手段 人类免疫后早期出现的天花，以及对疫苗的不良反应。我们的特定 目的就是从这一背景和理论基础出发的。

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.