%0 Journal Article
%A Muhs, A.
%A Hickmann, D.T.
%A Pihlgren, M.
%A Chuard, N.
%A Giriens, V.
%A Meerschman, C.
%A van der Auwera, I.
%A van Leuven, F.
%A Sugawara, M.
%A Weingertner, M.C.
%A Bechinger, B.
%A Greferath, R.
%A Kolonko, N.
%A Nagel-Steger, L.
%A Riesner, D.
%A Brady, R.O.
%A Pfeifer, A.
%A Nicolau, C.
%T Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice
%J Proceedings of the National Academy of Sciences of the United States of America
%V 104
%@ 0027-8424
%C Washington, DC
%I Academy
%M PreJuSER-60181
%P 9810 - 9815
%D 2007
%Z Record converted from VDB: 12.11.2012
%X 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.
%K Alzheimer Disease: prevention & control
%K Alzheimer Vaccines: immunology
%K Alzheimer Vaccines: pharmacology
%K Amyloid beta-Peptides: immunology
%K Amyloid beta-Peptides: metabolism
%K Amyloid beta-Protein Precursor: genetics
%K Analysis of Variance
%K Animals
%K Antigens: immunology
%K Brain: immunology
%K Brain: metabolism
%K Cytokines: metabolism
%K Enzyme-Linked Immunosorbent Assay
%K Epitope Mapping
%K Liposomes: immunology
%K Mice
%K Mice, Transgenic
%K Nuclear Magnetic Resonance, Biomolecular
%K Oligopeptides: genetics
%K Peptide Fragments: immunology
%K Recognition (Psychology): drug effects
%K Alzheimer Vaccines (NLM Chemicals)
%K Amyloid beta-Peptides (NLM Chemicals)
%K Amyloid beta-Protein Precursor (NLM Chemicals)
%K Antigens (NLM Chemicals)
%K Cytokines (NLM Chemicals)
%K Liposomes (NLM Chemicals)
%K Oligopeptides (NLM Chemicals)
%K PS1 antigen (NLM Chemicals)
%K Peptide Fragments (NLM Chemicals)
%K J (WoSType)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:17517595
%2 pmc:PMC1887581
%U <Go to ISI:>//WOS:000247114100049
%R 10.1073/pnas.0703137104
%U https://juser.fz-juelich.de/record/60181