Journal Article

FZJ-2026-04439

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Vaccines mimicking conformational epitopes on α-synuclein fibrils provide immunity to Parkinson’s disease

Ma, L. ; Reithofer, S. ; Pesch, V. ; Flores-Fernandez, J. M. ; Sriraman, A. ; Duckering, C. ; Amidian, S. ; Özdüzenciler, P.FZJ* ; Müller, L. ; Wille, H. ; Tamgüney, G. (Corresponding author)FZJ*

2026
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/brain/awag010  doi:10.34734/FZJ-2026-04439

Abstract: The progressive age-related aggregation of soluble α-synuclein into toxic oligomers and insoluble amyloid fibrils causes Parkinson’s disease, Lewy body dementia and multiple system atrophy, all of which are neurodegenerative diseases without a cure. Because α-synuclein is a self-antigen, pathogenic α-synuclein aggregates do not elicit astrong immune response. Recent advances in structural biology elucidating the structure of α-synuclein fibrils have allowed us to design engineered protein fibrils that model conformational epitopes present on the surface of α-synuclein fibrils. HET-s is a soluble fungal protein capable of forming amyloid fibrils. We used HET-s(218-298) fibrils and four modified derivatives, each displaying a selected conformational epitope present on the surface of α-synuclein fibrils, to vaccinate TgM83+/− mice, a model for Parkinson’s disease-like synucleinopathies. Fibrillar vaccine candidates significantly extended the survival of immunized TgM83+/− mice by ≤38% after intraperitoneal challenge and ≤42% after intragastric challenge with α-synuclein fibrils. Fully immunized mice developed antibodies that recognized α-synuclein fibrils and brain homogenates from patients with dementia with Lewy bodies, multiple system atrophy and Parkinson’s disease. Fibrillar vaccine candidates that mimic conformational epitopes on the surface of pathological α-synuclein fibrils have the ability to induce immunity and protection against Parkinson’s disease and other synucleinopathies.

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Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5244 - Information Processing in Neuronal Networks (POF4-524) (POF4-524)

Appears in the scientific report 2026

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Database coverage:
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