title: Vaccination with immunodominant peptides encapsulated in Quil A-containing liposomes induces peptide-specific primary CD8+ cytotoxic T cells.
abstract: Immunostimulating complexes (ISCOMs), containing lipids, the saponin Quil A, and proteinaceous antigens, have been proven to vaccinate effectively CD8+ cytolytic T cells in vivo. However, conventional ISCOM technology is restricted to hydrophobic proteins or fatty acid-derivatized proteins or peptides. We therefore analysed whether Quil A-containing liposomes are an effective vehicle to shuttle hydrophilic proteins or peptides into the MHC class I pathway of antigen presentation resulting in the in vivo induction of antigen-specific cytolytic T cells (CTL). Liposomes were formed by a lipid dry-down method followed by resuspension with an aqueous solution containing protein/peptide and Quil A and then an extrusion step. Quil A-containing liposomes are an effective means to elicit a CD8+ CTL response to peptide antigen in vivo. CTL could be raised in C57B1/6 mice against ovalbumin (OVA) peptide 257-264 and vesicular stomatitis virus nucleoprotein 52-59, as well as in Balb/c mice against listeriolysin peptide 91-99 and cytomegalovirus pp89 168-176, demonstrating the versatility of this approach. The elicited response was peptide-specific, peptide dose-dependent and Quil A was necessary. Vaccination with liposomes entrapping the whole ovalbumin molecule or an extended (OVA) peptide 254-276 also yielded a CTL responsive to the immunodominant OVA peptide 256-264, implying cellular internalization and correct processing. Thus Quil A-containing liposomes appear to be a versatile vehicle to vaccinate CD8+ T cells in vivo; in addition, they could rapidly enhance the understanding of subunit vaccines and rules of antigen processing and peptide-MHC class I binding.
authors.affiliation: Institute of Medical Microbiology and Hygiene, Technical University of Munich, Germany.
authors.forename: G B
authors.initials: GB
authors.lastname: Lipford
authors.forename: H
authors.initials: H
authors.lastname: Wagner
authors.forename: K
authors.initials: K
authors.lastname: Heeg
mesh_terms: D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D016827:CD8 Antigens; D002460:Cell Line; D002860:Chromium Radioisotopes; D016056:Immunodominant Epitopes / Q000276:immunology; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology*; D062605:Quillaja Saponins; D012503:Saponins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016827:CD8 Antigens; D002860:Chromium Radioisotopes; D016056:Immunodominant Epitopes; D008081:Liposomes; D010455:Peptides; D062605:Quillaja Saponins; D012503:Saponins; C046386:Quil A; D010047:Ovalbumin