Immunogenicity of epitope vaccines targeting different B cell antigenic determinants of human α-synuclein: feasibility study

Neuroscience Letters
Anahit GhochikyanMichael G Agadjanyan

Abstract

Immunotherapeutic approaches reducing α-synuclein deposits may provide therapeutic benefit for Dementia with Lewy Bodies (DLB). Immunization with full-length human α-synuclein (hα-Syn) protein in a Parkinson's disease mouse model decreased the accumulation of the aggregated forms of this protein in neurons and reduced neurodegeneration. To enhance the immunogenicity of candidate vaccines and to avoid the risk of autoreactive anti-hα-Syn T-helper (Th) cell responses, we generated three peptide-based epitope vaccines composed of different B-cell epitopes of hα-Syn fused with a "non-self" Th epitope from tetanus toxin (P30). Immunization of mice with these epitope vaccines produced high titers of anti-hα-Syn antibodies that bound to Lewy bodies (LBs) and Lewy neurites (LNs) in brain tissue from DLB cases and induced robust Th cell responses to P30, but not to hα-Syn. Further development of these first generation epitope vaccines may facilitate induction of anti-hα-Syn immunotherapy without producing potentially harmful autoreactive Th cell responses.

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Citations

Mar 10, 2016·Expert Review of Neurotherapeutics·Michael TolmasovYossi Gilgun-Sherki
Feb 24, 2017·Scandinavian Journal of Immunology·M von Euler Chelpin, T Vorup-Jensen
Apr 14, 2015·Immunity, Inflammation and Disease·Adahir Labrador-GarridoCintia Roodveldt
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Jun 15, 2021·Frontiers in Cell and Developmental Biology·Bipul RayMeena Kishore Sakharkar
May 6, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhipeng WangHui Yang

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