title: Highly efficient antiviral CD8+ T-cell induction by peptides coupled to the surfaces of liposomes.
abstract: In previous studies, we have demonstrated that liposomes with differential lipid components display differential adjuvant effects when antigens (Ags) are chemically coupled to their surfaces. When ovalbumin was coupled to liposomes made by using unsaturated fatty acids, it was found to be presented not only to CD4(+) T cells but also to CD8(+) T cells and induced cytotoxic T lymphocytes (CTLs) which effectively eradicated the tumor from mice. In this study, we coupled liposomes to immunodominant CTL epitope peptides derived from lymphocytic choriomeningitis virus (LCMV) and evaluated its potency as an antiviral vaccine. The intramuscular immunization of mice with the peptide-liposome conjugates along with CpG resulted in the efficient induction of antiviral CD8(+) T-cell responses which conferred complete protection against not only LCMV Armstrong but also a highly virulent mutant strain, clone 13, that establishes persistent infections in immunocompetent mice. The intranasal vaccination induced mucosal immunity effective enough to protect mice from the virus challenge via the same route. Complete protection was achieved in mice even when the Ag dose was reduced to as low as 280 ng of liposomal peptide. This form of vaccination with a single CTL epitope induced Ag-specific memory CD8(+) T cells in the absence of CD4(+) T-cell help, which could be shown by the complete protection of CD4-knockout mice in 10 weeks as well as by the analysis of recall responses. Thus, surface-linked liposomal peptide might have a potential advantage for the induction of antiviral immunity.
authors.affiliation: Department of Microbiology, Faculty of Medicine, Saitama Medical University, Iruma-gun, Saitama 350-0495, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Takagi
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsui
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohno
authors.forename: Hongying
authors.initials: H
authors.lastname: Duan
authors.forename: Osamu
authors.initials: O
authors.lastname: Moriya
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Oda
authors.forename: Masahito
authors.initials: M
authors.lastname: Mori
authors.forename: Akiharu
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Maiko
authors.initials: M
authors.lastname: Taneichi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Uchida
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Akatsuka
mesh_terms: D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001483:Base Sequence; D015704:CD4 Antigens / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D018928:Immunity, Mucosal; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000235:genetics; D007156:Immunologic Memory; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014764:Viral Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D015704:CD4 Antigens; C408982:CPG-oligonucleotide; D016056:Immunodominant Epitopes; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D014764:Viral Proteins; D010047:Ovalbumin
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