| Vaccination has dramatically reduced the rate of morbidity and mortality from many diseases. However, there are many existing and emerging disease-causing agents for which there are no successful vaccines and controlling these microbes will likely require a strong T cell-mediated immunity. Recombinant adenoviruses are potent inducers of cellular immunity, thus making them ideal platforms for T cell-based vaccines. Successful manipulation of the CD4+ and the CD8+ T cell compartment for the purpose of vaccination will undoubtedly rely on an in-depth of understanding of T cell activation, survival and function. The research documented in this thesis focuses on the characterization of the CD8+ T cell response induced by recombinant adenoviruses, in both CD4+ T cell-sufficient and deficient environments. In Chapter 3, we first determined that draining lymph nodes were the primary site of T cell activation following intramuscular immunization with a recombinant adenovirus and the activated CD8+ effectors rapidly migrated into the spleen. In Chapter 4, we extended our analysis to multiple tissues and to rime-points beyond the CD8+ T cell priming phase and established that rAd-induced CD8+ T cells exhibited unique characteristics associated with prolonged antigen stimulation. In Chapter 5, we explored the role of helper CD4+ T cells during CD8+ T cell priming and determined that help was required to maximize the primary CD8+ T cell response but the absence of CD4+ help did not appear to negatively impact the functionalities of the memory CD8+ T cells. This research provides novel insights into the CD8+ T cell response induced by recombinant adenovirus vectors and serves as an important biological foundation for future studies that aim to optimize, and perhaps customize, CD8+ T cell responses induced by adenovirus-based vaccines. |
