title: Virosome-based active immunization targets soluble amyloid species rather than plaques in a transgenic mouse model of Alzheimer's disease.
abstract: Active vaccination with amyloid peptides shows promise for the treatment and prevention of Alzheimer's disease (AD). Several studies in transgenic mouse models of AD have revealed the potency of vaccination to prevent or even clear amyloid plaques from mouse brain. However, the idea that soluble oligomeric species of beta-amyloid (Abeta), rather than plaques, trigger the disease has gained momentum, and current active vaccination strategies affect the levels of total or soluble brain Abeta little or not at all. We describe an active vaccination method based on Abeta1-16 presented on the surface of virosomes, which triggered a dramatic decrease in both soluble Abeta40 (75% reduction; p=0.01) and soluble Abeta42 (62% reduction; p=0.03) in a double transgenic mouse model of AD. Whereas Abeta40 and Abeta42 levels in the insoluble fraction tended to be reduced (by 30% and 27%, respectively), the number of thioflavine-S-positive amyloid plaques was not affected. The high specific antibody responses, obtained without eliciting T-cell reactivity, demonstrate that immunostimulating reconstituted influenza virosomes are a promising antigen carrier system against the neuropathology of AD.
authors.affiliation: Pevion Biotech Ltd., CH-3018 Bern, Switzerland. Rinaldo.zurbriggen@pevion.com
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Zurbriggen
authors.forename: Mario
authors.initials: M
authors.lastname: Amacker
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Kammer
authors.forename: Nicole
authors.initials: N
authors.lastname: Westerfeld
authors.forename: Peter
authors.initials: P
authors.lastname: Borghgraef
authors.forename: Fred
authors.initials: F
authors.lastname: Van Leuven
authors.forename: Ingrid
authors.initials: I
authors.lastname: Van der Auwera
authors.forename: Stefaan
authors.initials: S
authors.lastname: Wera
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D015415:Biomarkers; D001923:Brain Chemistry; D004195:Disease Models, Animal; D007114:Immunization; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D058225:Plaque, Amyloid / Q000276:immunology* / Q000473:pathology; D011897:Random Allocation; D022721:Vaccines, Virosome / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; D022721:Vaccines, Virosome