Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice

We investigated the therapeutic effects of two different versions of A beta(1-15 (16)) liposome-based vaccines. inoculation of APP-V717IxPS-1 (APPxPS-1) double-transgenic mice with tetrapalmitoylated amyloid 1-15 peptide (palmA beta 1-15), or with amyloid 1-16 peptide (PEG-A beta(1-16)) linked to a polyethyleneglycol spacer at each end, and embedded within a liposome membrane, elicited fast immune responses with identical binding epitopes. PaImA beta(1-15) liposomal vaccine elicited an immune response that restored the memory defect of the mice, whereas that of PEG-A beta(1-16) had no such effect. Immunoglobulins that were generated were predominantly of the IgG class with paimA beta(1-15), whereas those elicited by PEG-A beta(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. CID and NMR revealed predominantly P-sheet conformation of palmA beta(1-15) and random coil of PEG-A beta(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.