Investigating the contributions of inflammation and antigen depot to adjuvant function

The reasons why certain vaccine adjuvants and/or delivery systems are more or less effective at inducing immune responses or promoting the preferential induction of particular types of response are unknown. Specifically, it is unclear what impact inflammatory and depot-forming adjuvants have on APC factors known to regulate these responses, in particular phenotype, activation state, magnitude and duration of antigen presentation and the consequences these factors have on T cell activation, differentiation and function. Furthermore, very few of these parameters have been defined for these agents in vivo. This is a significant omission as it is clear that the component parts of the immune system do not work in isolation and their interactions are dynamic and occur in distinct and specialised micro- and macroanatomical locations that can only be fully determined in real time, in the physiological context, in vivo. Therefore, we are analysing the impact that inflammatory and depot-forming adjuvants have on the phenotype, activation state, processing and presenting capacity of APC and the subsequent consequences of this for T cell activation, differentiation and function. Only by performing such detailed and fundamental studies in vivo can we fully understand the cellular and molecular interactions that control the immune response. This information is a prerequisite if we are truly to design, build and target vaccines and therapeutic strategies effectively