Format

Send to

Choose Destination
See comment in PubMed Commons below
Neurosci Lett. 2014 Feb 7;560:86-91. doi: 10.1016/j.neulet.2013.12.028. Epub 2013 Dec 19.

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

Author information

1
The Institute for Molecular Medicine, Department of Immunology, Huntington Beach, CA 92647, United States. Electronic address: aghochikyan@immed.org.
2
The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, United States.
3
The Institute for Molecular Medicine, Department of Immunology, Huntington Beach, CA 92647, United States; The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, United States.
4
The Institute for Molecular Medicine, Department of Immunology, Huntington Beach, CA 92647, United States.
5
The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, United States; Department of Neurology, University of California, Irvine, CA 92697, United States.
6
The Institute for Molecular Medicine, Department of Immunology, Huntington Beach, CA 92647, United States; The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, United States. Electronic address: magadjanyan@immed.org.

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.

KEYWORDS:

B cell epitope of α-synuclein; Epitope vaccine; Immunotherapy; Parkinson's and Alzheimer's diseases; T cell epitope of tetanus toxin

PMID:
24361548
PMCID:
PMC3928627
DOI:
10.1016/j.neulet.2013.12.028
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center