title: Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice.
abstract: We investigated the therapeutic effects of two different versions of Abeta(1-15 (16)) liposome-based vaccines. Inoculation of APP-V717IxPS-1 (APPxPS-1) double-transgenic mice with tetra-palmitoylated amyloid 1-15 peptide (palmAbeta(1-15)), or with amyloid 1-16 peptide (PEG-Abeta(1-16)) linked to a polyethyleneglycol spacer at each end, and embedded within a liposome membrane, elicited fast immune responses with identical binding epitopes. PalmAbeta(1-15) liposomal vaccine elicited an immune response that restored the memory defect of the mice, whereas that of PEG-Abeta(1-16) had no such effect. Immunoglobulins that were generated were predominantly of the IgG class with palmAbeta(1-15), whereas those elicited by PEG-Abeta(1-16) were primarily of the IgM class. The IgG subclasses of the antibodies generated by both vaccines were mostly IgG2b indicating noninflammatory Th2 isotype. CD and NMR revealed predominantly beta-sheet conformation of palmAbeta(1-15) and random coil of PEG-Abeta(1-16). We conclude that the association with liposomes induced a variation of the immunogenic structures and thereby different immunogenicities. This finding supports the hypothesis that Alzheimer's disease is a "conformational" disease, implying that antibodies against amyloid sequences in the beta-sheet conformation are preferred as potential therapeutic agents.
authors.affiliation: AC Immune, PSE-B, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Muhs
authors.forename: David T
authors.initials: DT
authors.lastname: Hickman
authors.forename: Maria
authors.initials: M
authors.lastname: Pihlgren
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chuard
authors.forename: Valérie
authors.initials: V
authors.lastname: Giriens
authors.forename: Carine
authors.initials: C
authors.lastname: Meerschman
authors.forename: Ingrid
authors.initials: I
authors.lastname: van der Auwera
authors.forename: Fred
authors.initials: F
authors.lastname: van Leuven
authors.forename: Masae
authors.initials: M
authors.lastname: Sugawara
authors.forename: Marie-Catherine
authors.initials: MC
authors.lastname: Weingertner
authors.forename: Burkhard
authors.initials: B
authors.lastname: Bechinger
authors.forename: Ruth
authors.initials: R
authors.lastname: Greferath
authors.forename: Nadine
authors.initials: N
authors.lastname: Kolonko
authors.forename: Luitgard
authors.initials: L
authors.lastname: Nagel-Steger
authors.forename: Detlev
authors.initials: D
authors.lastname: Riesner
authors.forename: Roscoe O
authors.initials: RO
authors.lastname: Brady
authors.forename: Andrea
authors.initials: A
authors.lastname: Pfeifer
authors.forename: Claude
authors.initials: C
authors.lastname: Nicolau
mesh_terms: D000544:Alzheimer Disease / Q000517:prevention & control*; D023582:Alzheimer Vaccines / Q000276:immunology* / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D008081:Liposomes / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000235:genetics; D010446:Peptide Fragments / Q000276:immunology; D021641:Recognition, Psychology / Q000187:drug effects*
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000941:Antigens; D016207:Cytokines; D008081:Liposomes; D009842:Oligopeptides; C449186:PS1 antigen; D010446:Peptide Fragments