Towards Alzheimer's beta-amyloid vaccination.
Beta-amyloid pathology, the main hallmark of Alzheimer's disease (AD), has been linked to its conformational status and aggregation. We recently showed that site-directed monoclonal antibodies (mAbs) towards the N-terminal region of the human beta-amyloid peptide bind to preformed beta-amyloid fibrils (Abeta), leading to disaggregation and inhibition of their neurotoxic effect. Here we report the development of a novel immunization procedure to raise effective anti-aggregating amyloid beta-protein (AbetaP) antibodies, using as antigen filamentous phages displaying the only EFRH peptide found to be the epitope of these antibodies. Due to the high antigenicity of the phage no adjuvant is required to obtain high affinity anti-aggregating IgG antibodies in animals model, that exhibit identity to human AbetaP. Such antibodies are able to sequester peripheral AbetaP, thus avoiding passage through the blood brain barrier (BBB) and, as recently shown in a transgenic mouse model, to cross the BBB and dissolve already formed beta-amyloid plaques. To our knowledge, this is the first attempt to use as a vaccine a self-anti-aggregating epitope displayed on a phage, and this may pave the way to treat abnormal accumulation-peptide diseases, such as Alzheimer's disease or other amyloidogenic diseases.
Frenkel
D
D
Department of Molecular Microbiology and Biotechnology, Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 69978, Israel.
Solomon
B
B
D000544:Alzheimer Disease / Q000517:prevention & control*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D001435:Bacteriophages / Q000235:genetics; D000939:Epitopes / Q000008:administration & dosage* / Q000737:chemistry; D005455:Fluorescent Antibody Technique; D006801:Humans; D016716:PC12 Cells; D051381:Rats; D014614:Vaccines, Synthetic / Q000008:administration & dosage*
D016229:Amyloid beta-Peptides; D000939:Epitopes; D014614:Vaccines, Synthetic