Immunization against Alzheimer's β -amyloid Plaques via EFRH Phage Administration

The epitope EFRH, corresponding to amino acids 3-6 within the human β -amyloid peptide (Aβ P) acts as a regulatory site controlling both the formation and disaggregation process of the β -amyloid fibrils (Aβ ). Locking of this epitope by highly specific antibodies affects the dynamics of the entire...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2000-10, Vol.97 (21), p.11455-11459
Main Authors: Frenkel, Dan, Katz, Odelia, Solomon, Beka
Format: Article
Language:English
Subjects:
Alzheimer Disease - immunology
Alzheimer's disease
Alzheimers disease
Amino Acid Sequence
Amino acids
Amyloid beta-Peptides - immunology
Animals
Antibodies
Antibodies - immunology
Antigens
Bacteriophages
Bacteriophages - genetics
Bacteriophages - immunology
Biological Sciences
Enzyme linked immunosorbent assay
Epitopes
Humans
Immune Sera
Immunization
Immunology
Mice
Mice, Inbred BALB C
Oligopeptides - administration & dosage
Oligopeptides - immunology
PC12 Cells
Peptides
Rats
Solar fibrils
Vaccination
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Summary:The epitope EFRH, corresponding to amino acids 3-6 within the human β -amyloid peptide (Aβ P) acts as a regulatory site controlling both the formation and disaggregation process of the β -amyloid fibrils (Aβ ). Locking of this epitope by highly specific antibodies affects the dynamics of the entire Aβ P molecule, preventing self-aggregation as well as enabling resolubilization of already formed aggregates. Production of such antibodies by repeated injections of toxic human Aβ fibrils into transgenic mice suggests the feasibility of vaccination against Alzheimer's disease. Here, we report the development of an immunization procedure for the production of effective anti-aggregating β -amyloid antibodies based on filamentous phages displaying the EFRH peptide as specific and nontoxic antigen. Effective autoimmune antibodies were obtained by EFRH phage administration in guinea pigs, which exhibit Aβ P identical to the human Aβ P region. Moreover, because of the high antigenicity of the phage, no adjuvant is required to obtain high affinity anti-aggregating IgG antibodies after a short immunization period of 3 weeks. Availability of such antibodies opens up possibilities for the development of an efficient and long-lasting vaccination for the prevention and treatment of Alzheimer's disease.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.97.21.11455