Recent findings about pathogens and innate immune system interactions 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 (Nm) to form very small size proteoliposomes (VSSP). VSSP, used as monotherapy, demonstrated a unique ability to render immunogenic highly tolerated gangliosides. These results drove our attention to the immunopotentiating properties of VSSP. Here, we examined the VSSP adjuvant effect on the humoral and cellular responses, dendritic cell (DC) activation, and differentiation of Th cells. Also, the role of LPS in VSSP effect was dissected. This study reveals that VSSP is a potent adjuvant for dendritic cells activation and Th1 differentiation. © 2004 Elsevier Ltd. All rights reserved.