This application is for an R21 Planning Grant for the CCTRHIB program. During the one-year tenure of this grant, we will accomplish three aims. First we will organize clinical and research investigators into a center dedicated to the study of human immune responses to infectious agents. We will emphasize and encourage the work to be aimed at microbes with the potential as bioterrorist agents. Organization of the center will included the creation of a seminar series, work in progress series and a journal club. A session devoted to human immunity and bioterrorist agents will be included in a twice yearly symposium at the New York Academy of Sciences. During this year we will develop the rationale and research design for the Translational Center. As currently envisioned the center will be devoted to the development of technology and research relating to viral proteins which function to block innate immunity or the initiation of specific immunity. It is expected that through studies of this type information will be gathered that will allow the development of mutant viruses for use as vaccines. Additionally, viral genes will be inserted into live virus vectors and tested for their immunogenicity and innate immune stimulating activity in human cell systems. In keeping with the current rationale of the center, human primary cells will be used in assays of both innate and the initiation of specific immunity. During the tenure of the R21 we will develop techniques for collecting and growth of human epithelial cells from different target tissue. We will also locate possible sources of tissue in order to grow cells from patients of varying age, sex, and ethnicity. Techniques for large-scale growth of dendritic cells will also be developed. The viral agents, mutant viruses or developed vectors containing viral genes will be tested in these cells to determine their effects on the maturation of DCs. Additionally, the infected DC will be tested for their ability to stimulate immune responses using human T cells. This work is aimed to develop an interactive group of investigators with common interests and goals that will lead to the submission of a U19 grant for creation of a Translational Center devoted to the study of Human Immunology and microbes with the potential to be used as bioterrorist agents.
