Fusogenic potential of prokaryotic membrane lipids - Implication in vaccine development

Development of protective immunity against many pathogens, particularly vir uses, requires fine orchestration of both humoral- and cell mediated-immuni ty. The immunization of animals with soluble antigens usually leads to the induction of humoral immune responses. In contrast, the activation of a cel l-mediated immune response against exogenous antigens has always been a cha llenge, requiring special strategies to expose them to the proteasome, a mu ltifunctional protease complex in the cytosol of the target cells. The degr adation of the protein by the cytosolic proteolytic system forms a cardinal step for the induction of cytotoxic T lymphocytes (CTLs). In the present s tudy, we report that a potent primary CTL response against a soluble protei n, ovalbumin, can be induced in mice by encapsulating it in the liposomes c omprised of Escherichia coli membrane lipids. These lipids were shown to in duce strong membrane-membrane fusion as evident from resonance energy trans fer and content mixing assays. Furthermore, the fusion of these liposomes w ith living cells (J774 Al) was demonstrated to result in effective transfer of a fluorescent lipid probe to the plasma membrane of the cells. Moreover , ricin A, a protein synthesis inhibitor that does not cross plasma membran e, was demonstrated to gain access to the cytosol when it was encapsulated in these liposomes. Finally, the liposomes were demonstrated to behave like efficient vehicles for the in vivo delivery of the antigens to the target cells resulting in the elicitation of antigen reactive CD8(+) T cell respon ses.