Mechanism of liposome adjuvanticity: an in vivo approach

The reputation of liposomes as adjuvant of the immune response is now firmly established despite the lack of information on the mechanisms involved in their immunopotentiating properties. The rapid targeting of massive doses of antigenic material to antigen-presenting cells, especially macrophages has, however, often been invoked as the principal source of liposomal adjuvanticity. In order to test this hypothesis, we analyzed the humoral response to antigen encapsulated in liposomes containing increasing amounts of surface-exposed mannose residues, ligand specific of an exclusive macrophagic receptor. Using BSA as a model antigen, we demonstrated that the humoral response is profoundly affected by mannosylation, being of prolonged duration and either inhibited or activated depending on the immunizing doses. These results suggest that the rapidity of antigen targeting is not the sole reason to liposome adjuvanticity and that the role of liposomes as antigenic depot is probably important to sustain substantial activation through successive restimulations. In this context, the increased rapidity in antigen targeting which favors the concentration of activation signals in time, results in an under-optimization of the response at high immunizing doses and in an optimization of this response at doses that would otherwise give rise to signal of sub-threshold intensity albeit during a longer period of time.