Immunization against Alzheimer's beta -amyloid plaques via EFRH phage administration.
The epitope EFRH, corresponding to amino acids 3-6 within the human beta-amyloid peptide (AbetaP), acts as a regulatory site controlling both the formation and disaggregation process of the beta-amyloid fibrils (Abeta). Locking of this epitope by highly specific antibodies affects the dynamics of the entire AbetaP molecule, preventing self-aggregation as well as enabling resolubilization of already formed aggregates. Production of such antibodies by repeated injections of toxic human Abeta 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 beta-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 AbetaP identical to the human AbetaP 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.
Frenkel
D
D
Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 69978, Israel.
Katz
O
O
Solomon
B
B
D000544:Alzheimer Disease / Q000276:immunology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001435:Bacteriophages / Q000235:genetics / Q000276:immunology; D006801:Humans; D007106:Immune Sera; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000008:administration & dosage* / Q000276:immunology; D016716:PC12 Cells; D051381:Rats
D016229:Amyloid beta-Peptides; D000906:Antibodies; D007106:Immune Sera; D009842:Oligopeptides