Pilot Projects Component (Pilot Proj 2: Guccione)

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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.