MOLECULAR SIGNATURES OF IMMUNE RESPONSE TO VACCINATION

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In order to define the critical determinants of successful vaccination, it is crucial to identify the global signatures of the associated immune response. We propose to identify these signatures through the application of a combination of high-throughput mRNA technologies, proteomic technologies, and computational tools. The aim of the genomics core is to provide high-throughput sequencing and microarray facilities for investigators in the vaccine consortium. Sequencing facilities will be available to analyze cDNA libraries, which will be utilized for customized array construction. The microarray facilities will be used for analysis of mRNA expression profiles in populations of different immune cells under various stimulatory conditions. The aim of the proteomics core is to assist the center investigators in quantitatively defining proteomic changes in immune cells as they respond to immunization. The focus of the analyses is to characterize specific changes within the proteomes of immune cells (T and B lymphocytes and dendritic cells), and within patients' sera. These studies aim to elucidate changes in membrane glycoproteins (co-stimulation and trafficking), cytosolic phosphoproteins (signal transduction), and nuclear proteins (gene expression and cellular differentiation). Serum glycoproteins will be quantitated at early and later time points postimmunization to identify humoral factors that correlate with the development of an effective memory immune response. The bioinformatics core will provide a central repository for the storage of data in a standardized format, which will permit data from a variety of different techniques to be analyzed, integrated and shared between investigators. The core will provide software tools to enable researchers to explore the data, make comparisons between data sets, to interrogate data sets with specific hypotheses, and to globally interrogate data sets to identify novel patterns and associations among disparate data sources. Tools also will be provided to simultaneously visualize and integrate multi-dimensional data sets. These computational tools will be essential for extracting meaningful insight from the relationships between individual molecules and systemic, immune responses to vaccination.