Assessing the molecular mechanisms of novel vaccine adjuvants for generation of optimal killer T cell immunity.

A cardinal feature of adaptive CD8+ T cell (also known as killer T cells) responses to infection is the rapid initiation of a proliferative response that coincides with acquisition of lineage-specific functions by pathogen-specific T cells. This enables the identification and removal of virus infected host cells. Once an infection is cleared, the expanded effector killer T cell population contracts, leaving a pool of long-lived, pathogen-specific memory T cells. In contrast to naïve CD8+ T cells, virus-specific memory CTLs are able to respond more readily and rapidly to subsequent infections, and without the need for further differentiation. This function enables rapid control of a secondary infection leading to immune protection. It is of paramount importance to harness killer T cell immunity for the development of vaccines and therapies for a variety of disease states. This includes infections, such as malaria, for which there are no effective vaccine strategies but for which T cell immunity is a strong correlate of protection. Moreover, there is a compelling need to augment current vaccine strategies to infections caused by influenza a virus (IAV), where T cell immunity is important for protection from disease when humoral (antibody immunity) is ineffective. This project will assess the capacity of novel vaccine formulations to induce robust killer T cell immunity to Influenza A virus using a combination of advanced molecular techniques such as single cell RNA-seq, ChIP-seq, ATAC-seq. When compared to immunity induced by IAV infection, this will not only provide a way of evaluating vaccine effectiveness, but will aslo provide key information about the molecular pathways that are utilised to establish optimal T cell immunity.