Dendritic cells (DCs) are essential for the stimulation of protective immunity and therefore play a central role in vaccination. The skin is now emerging as an attractive site for vaccination due to its dense population of immune cells, including DCs. Understanding the ways in which distinct DC subsets can be targeted and activated by vaccine components may allow us to enhance and tailor immune responses to elicit more robust protection against unconquered infections such as HIV. To this end we have utilised a rhesus macaque model for intramuscular vaccination and observed the early innate immune response mounted against distinct adjuvants (alum, alum containing a TLR7 ligand or MF59) as well as the initiation of an adaptive response by tracking the uptake, transport to the draining lymph nodes and presentation of fluorescently labelled vaccine antigens to T cells. This project revealed distinct innate immune profiles of the different adjuvants and the functional specialisation of different DC subsets. Following on from this we are now developing a corresponding in vivo macaque model to study skin vaccination. Phenotypic characterisation of human and macaque skin DC subsets confirms that they are quite distinct from those found in blood and likely differ in their functions and response to vaccine components. Such a model could be a powerful tool for studying how vaccines work in humans and could yield data that can be translated into optimising future vaccine formulations specifically for the skin.