Immunization against Alzheimer's β-amyloid plaques via EFRH phage administration

The epitope EFRH. corresponding to amino acids 3-6 within the human beta-amyloid peptide (A beta P). acts as a regulatory site controlling both the formation and disaggregation process of the beta-amyloid fibrils (A beta). Locking of this epitope by highly specific antibodies affects the dynamics of the entire A beta P molecule, preventing self-aggregation as well as enabling resolubilization of already formed aggregates. Production of such antibodies by repeated injections of toxic human A beta 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 A beta P identical to the human A beta 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.