Frenkel D, Katz O, Solomon B.
Immunization against Alzheimer's beta -amyloid plaques via EFRH phage administration.Proc Natl Acad Sci U S A.
The epitope EFRH, corresponding to amino acids 3-6 within the human b-amyloid peptide (AbP), acts as a regulatory site controlling both the formation and disaggregation process of the b-amyloid fibrils (Ab). Locking of this epitope by highly specific antibodies affects the dynamics of the entire AbP molecule, preventing self-aggregation as well as enabling resolubilization of already formed aggregates. Production of such antibodies by repeated injections of toxic human Ab 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 b-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 AbP identical to the human AbP 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 three 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.