Despite significant effort over the past decade to design and implement new vaccines strategies against HIV, no one has met its promise to prevent infection and/or to reduce viral load until reaching eradication of the HIV reservoir. To reach this goal, a translational research is critical to propose innovative approaches for an HIV vaccine enhancing broadly cross-reactive mucosal, humoral and cellular immune responses specific to HIV antigens. Composed by 13 partners from 5 European countries and 2 International Cooperation countries, the CUT’HIVAC consortium gathers knowledge’s and cutting-edge technologies in vaccinology and HIV diseases to raise the challenge of developing a new HIV strategy. The CUT’HIVAC approach is based on innovative transcutaneous and/or mucosal needle-free vaccination methods in a perspective that new vaccine candidates will redirect immune response toward cytotoxic CD8 and mucosal humoral responses. The trust of the project derives from the proof-of-concept that combination of routes of immunization and delivery systems will shape the immune responses towards its protective arms against HIV. Clinical trials will be implemented with last cutting-edge generation of HIV DNA-GTU® candidate applied by transcutaneous, intradermal routes and/or mucosal administration of HIV-envelop protein-based vaccine. Large efforts will be positioned on the new genetic design of HIV antigens and delivery systems for developed and developing countries. These new vaccines will be tested in innovative preclinical approaches with a special highlight on routes of vaccination that will be translated into 2nd round of clinical trials in a perspective that could help to prevent and eradicate HIV. Through its integrative and multidisciplinary approach, CUT’HIVAC will therefore provide the basis for a novel approach in vaccination with a view to wide its application to other infectious diseases such as malaria and tuberculosis.