Vaccinia and Dengue viruses: Exploring current fundamental issues of memory T cells and utilizing quantitative immunology to compare correlates of protection following smallpox immunization

Memory T cells often perform an important role in mediating viral clearance upon secondary viral infection. Therefore, expanding the current understanding of issues surrounding memory T cell development, the long term maintenance and the functional characteristics of different memory subsets is essential. A deeper understanding of these issues surrounding memory T cells will aid in generating more successful vaccines. The unsuccessful attempts to create vaccines to protect against devastating diseases such as HIV and malaria have highlighted the flaws in traditional approaches of developing empirically derived vaccines. Data obtained from the following studies can be used and applied to rationally attain new, 21st century vaccines. The work presented here focuses on two viruses, vaccinia and Dengue. However, the questions addressed have implications beyond these two pathogens. Here we present findings on the long term maintenance and functional properties of effector and central memory T cells in humans last vaccinated with vaccinia virus over 30 years previously. These data provides a basis for a quantitative immunological comparison after administration of new smallpox vaccines. Utilizing a mouse model of vaccinia infection, we then address how antigen duration and the induction of inflammation effects memory T cell development. Finally, the four serotyes of Dengue virus provided us with an opportunity to study heterologous infection and the possible detrimental effects of partial T cell agonists on memory T cells.