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Fusogenic potential of prokaryotic membrane lipids.â: Implication in vaccine development
- Ahmad, N., Masood, A. K., Owais, M.
- European journal of biochemistry 2001 v.268 no.22 pp. 5667-5675
- Escherichia coli, antigens, cell-mediated immunity, cytosol, cytotoxic T-lymphocytes, encapsulation, energy transfer, fluorescence, humoral immunity, immunization, lipids, mice, ovalbumin, pathogens, plasma membrane, proteasome endopeptidase complex, protein degradation, protein synthesis inhibitors, proteinases, proteolysis, ricin, vaccine development, viruses
- Development of protective immunity against many pathogens, particularly viruses, requires fine orchestration of both humoralâ and cell mediatedâimmunity. The immunization of animals with soluble antigens usually leads to the induction of humoral immune responses. In contrast, the activation of a cellâmediated immune response against exogenous antigens has always been a challenge, requiring special strategies to expose them to the proteasome, a multifunctional protease complex in the cytosol of the target cells. The degradation of the protein by the cytosolic proteolytic system forms a cardinal step for the induction of cytotoxic T lymphocytes (CTLs). In the present study, we report that a potent primary CTL response against a soluble protein, ovalbumin, can be induced in mice by encapsulating it in the liposomes comprised of Escherichia coli membrane lipids. These lipids were shown to induce strong membraneâmembrane fusion as evident from resonance energy transfer and content mixing assays. Furthermore, the fusion of these liposomes with living cells (J774âA1) 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 membrane, 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 responses.