The recent recognition of innate immune activation as a critical driver of the adaptive immune response has major implications for vaccine development, and adjuvant research in particular. Using a unique and well established sheep model of pseudoafferent lymphatic cannulation, we investigated the kinetics of antigen transport and the innate inflammatory response in the afferent lymph draining the site of vaccination. Our studies demonstrated, for the first time, the in vivo effect of aluminium hydroxide adjuvant on soluble antigen flow and that aluminium hydroxide enhances particulate antigen uptake by dendritic cells at later time points ¹. In contrast, monophosphoryl lipidA (MPL) enhanced neutrophil and monocyte recruitment but had no effect on antigen uptake by DCs². We have expanded this analysis to other classes of adjuvant including oil in water, and liposomes with/without the immunomodulators poly I:C and CpG. Both dramatic and subtle differences were observed in antigen uptake by afferent lymph cells over time and in the cell types recruited into the lymph following injection of the different adjuvant formulations. Next generation sequencing of mRNA derived from afferent lymph cells has revealed dramatic effects on gene expression by a TLR agonist over time, indicating that distinct molecular profiles can be generated for different adjuvant formulations. Further exploitation of this unique model will allow us to home in on the different cellular and molecular pathways that are activated by different adjuvants in vivo, and how they determine the physiological and immunological responses that impact on vaccine efficacy and safety.