TY  - JOUR
AU  - Muhs, A.
AU  - Hickmann, D.T.
AU  - Pihlgren, M.
AU  - Chuard, N.
AU  - Giriens, V.
AU  - Meerschman, C.
AU  - van der Auwera, I.
AU  - van Leuven, F.
AU  - Sugawara, M.
AU  - Weingertner, M.C.
AU  - Bechinger, B.
AU  - Greferath, R.
AU  - Kolonko, N.
AU  - Nagel-Steger, L.
AU  - Riesner, D.
AU  - Brady, R.O.
AU  - Pfeifer, A.
AU  - Nicolau, C.
TI  - Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 104
SN  - 0027-8424
CY  - Washington, DC
PB  - Academy
M1  - PreJuSER-60181
SP  - 9810 - 9815
PY  - 2007
N1  - Record converted from VDB: 12.11.2012
AB  - 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.
KW  - Alzheimer Disease: prevention & control
KW  - Alzheimer Vaccines: immunology
KW  - Alzheimer Vaccines: pharmacology
KW  - Amyloid beta-Peptides: immunology
KW  - Amyloid beta-Peptides: metabolism
KW  - Amyloid beta-Protein Precursor: genetics
KW  - Analysis of Variance
KW  - Animals
KW  - Antigens: immunology
KW  - Brain: immunology
KW  - Brain: metabolism
KW  - Cytokines: metabolism
KW  - Enzyme-Linked Immunosorbent Assay
KW  - Epitope Mapping
KW  - Liposomes: immunology
KW  - Mice
KW  - Mice, Transgenic
KW  - Nuclear Magnetic Resonance, Biomolecular
KW  - Oligopeptides: genetics
KW  - Peptide Fragments: immunology
KW  - Recognition (Psychology): drug effects
KW  - Alzheimer Vaccines (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Amyloid beta-Protein Precursor (NLM Chemicals)
KW  - Antigens (NLM Chemicals)
KW  - Cytokines (NLM Chemicals)
KW  - Liposomes (NLM Chemicals)
KW  - Oligopeptides (NLM Chemicals)
KW  - PS1 antigen (NLM Chemicals)
KW  - Peptide Fragments (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:17517595
C2  - pmc:PMC1887581
UR  - <Go to ISI:>//WOS:000247114100049
DO  - DOI:10.1073/pnas.0703137104
UR  - https://juser.fz-juelich.de/record/60181
ER  -