A Novel C-Type Lectin Receptor-Targeted α-Synuclein-Based Parkinson Vaccine Induces Potent Immune Responses and Therapeutic Efficacy in Mice

Autor: Sabine Schmidhuber, Sandra Scheiblhofer, Richard Weiss, Mihály Cserepes, József Tóvári, Gabriele Gadermaier, Erwan Bezard, Francesca De Giorgi, François Ichas, Dirk Strunk, Markus Mandler
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Vaccines, Vol 10, Iss 9, p 1432 (2022)
Druh dokumentu: article
ISSN: 10091432
2076-393X
DOI: 10.3390/vaccines10091432
Popis: The progressive accumulation of misfolded α-synuclein (α-syn) in the brain is widely considered to be causal for the debilitating clinical manifestations of synucleinopathies including, most notably, Parkinson’s disease (PD). Immunotherapies, both active and passive, against α-syn have been developed and are promising novel treatment strategies for such disorders. To increase the potency and specificity of PD vaccination, we created the ‘Win the Skin Immune System Trick’ (WISIT) vaccine platform designed to target skin-resident dendritic cells, inducing superior B and T cell responses. Of the six tested WISIT candidates, all elicited higher immune responses compared to conventional, aluminum adjuvanted peptide-carrier conjugate PD vaccines, in BALB/c mice. WISIT-induced antibodies displayed higher selectivity for α-syn aggregates than those induced by conventional vaccines. Additionally, antibodies induced by two selected candidates were shown to inhibit α-syn aggregation in a dose-dependent manner in vitro. To determine if α-syn fibril formation could also be inhibited in vivo, WISIT candidate type 1 (CW-type 1) was tested in an established synucleinopathy seeding model and demonstrated reduced propagation of synucleinopathy in vivo. Our studies provide proof-of-concept for the efficacy of the WISIT vaccine technology platform and support further preclinical and clinical development of this vaccine candidate.
Databáze: Directory of Open Access Journals
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