The need to develop vaccines against challenging diseases such as malaria or tuberculosis requires effective adjuvants to improve the immune responses against purified antigens, as these antigens often lack intrinsic immunogenicity. Most adjuvants act on innate immunity leading to the activation of antigen presenting cells and induction of memory T cell and antibody responses to the vaccine. Including more than one immunostimulant within an adjuvant has the capacity to improve the quality of the immune response to a vaccine. In this respect, combinatorial adjuvants may emulate aspects of the natural immune response to a pathogen, which involves multiple innate pathways typically triggered by stimuli from pathogen-derived molecules. GSK Vaccines has pioneered the use of immunostimulants in adjuvant formulations for human vaccines. One of its propriety Adjuvant Systems, AS01, is a liposome-based and contains the immunostimulants MPL and QS-21. In pre-clinical models, antigen-specific cellular immune responses are synergistically enhanced with the combination of MPL and QS-21. Hence the overall scientific objective of the ADJSYN project is to understand the basis of the MPL and QS-21 synergy by focussing on key molecular and cellular mediators of the synergistic response, and on how these mediators interact. This project will use a multidisciplinary approach, involving bioinformatics, immunology, imaging and molecular biology, and will be conducted through several collaborations within Europe. Therefore ADJSYN should deliver mechanistic insights on how to engage innate immune pathways to promote effective adaptive immune responses; and the methodology should be transferable for the analysis of adjuvants formulated with other immunostimulants. Moreover, because AS01 is being evaluated in an increasing number of vaccines, the insights from this project could have direct relevance for translational research and the rationale design of new human vaccines.