Liposome-based Co-delivery of Adjuvants and Peptide Antigens: Application to the Development of Synthetic Vaccines

Introduction: Subunit vaccines represent an important aspect of modern vaccination. In this respect, the possibility to construct peptide-based vaccines is particularly appealing and peptides that e.g. mimic epitopes of pathogens, can be designed to induce well-defined monofunctional immune responses. Multi-epitopic constructs that contain epitopes from the same and/or different pathogen(s) can also be envisaged. Similarly, constructs that combine CTL epitopes representative of tumor-associated antigens and Th epitopes are the basis of active cancer immunotherapy (prophylactic and therapeutic vaccination). However, despite their interest, the impact of peptides in the development of effective means for the prevention of infectious eases and treatment of tumors is, so far, somewhat limited. This is mainly due to the low immunogenicity of peptides and the paucity of effective adjuvants; within this context liposomes are of great interest as carriers of peptide antigens and of immunoadjuvants. Liposomes are characterized by a low toxicity and a low intrinsic immunogenicity (no carrier epitopic suppression). They can carry antigens (and adjuvants) either surface-bound, encapsulated or membraneassociated. Moreover, their physicochemical properties (size, pH-sensitivity, bilayer rigidity,..) can be manipulated to influence the mode of antigen presentation. Indeed, it was noted decades ago that these vesicles are able to increase the immune response against poorly immunogenic proteins/peptides that were associated to them (1). During this talk I will give two examples of synthetic vaccination constructs we have developped: i) an anti-bacterial vaccine which triggers a powerful humoral (CD4) immune response (production of antibodies), and ii) an antitumoral vaccine that elicits a specific cellular (CD8) immune response. Design of highly immunogenic liposomal peptide diepitope constructs: Our aim was to reproduce, with simple liposomal constructs, the presentation by a pathogen of antigens to the immune system. To that end we have designed diepitope constructs that combine synthetic B and Th epitopes. We have devised a strategy that allows a chemically controlled coupling of two different peptides to the same preformed liposome on two different hydrophobic anchors (Fig. 1). This design allows the association at the surface of a same vesicle of two epitopes which remain independent from a molecular standpoint and thus may have different fates with regard to the immunocompetent cells.