Recent findings in the interactions between pathogens and the innate immune system, particularly with dendritic cells (DC), have opened new opportunities for adjuvants designs. We have elaborated a new approach, in which gangliosides are incorporated into the outer membrane complex of Neisseria meningitidis to form very small size proteoliposomes (VSSP). VSSP demonstrated a unique ability to render highly tolerated gangliosides immunogenic. These results drove our attention to the immunopotentiating properties of VSSP. Here we examined the VSSP adjuvant effect on dendritic cell activation. Also the role of LPS on this effect was dissected. This study reveals that VSSP is a potent adjuvant for DC activation. © 2005 Elsevier Ltd. All rights reserved.