Generation of auto-antibodies towards Alzheimer's disease vaccination.
We developed a novel procedure to evoke anti-aggregating beta-amyloid (Abeta) antibodies, using filamentous phages displaying only four amino acids EFRH of the beta-amyloid peptide (AbetaP). This epitope was found to be the main regulatory site for fibril formation. For the first time, effective auto-antibodies have been obtained in guinea-pigs, which exhibit human identity in the AbetaP. Immunization through a phage-carrying epitope was found to be long-lasting, and no toxic effect caused by autoimmune response was detected in the challenged animal sections. These antibodies performed similarly to site-directed monoclonal antibodies and to antibodies raised against fibrillar Abeta in disaggregation of plaques, and may serve as the basis for developing an anti-Abeta vaccine.
Department of Molecular Microbiology and Biotechnology, Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, 69978, Tel-Aviv, Israel.
D
D
Frenkel
N
N
Kariv
B
B
Solomon
D000544:Alzheimer Disease / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001435:Bacteriophages / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D006168:Guinea Pigs; D006801:Humans; D016716:PC12 Cells; D051381:Rats; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D001323:Autoantibodies; D000939:Epitopes; D014614:Vaccines, Synthetic