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.