Open AccessImmunization against Alzheimer's β-amyloid plaques via EFRH phage administration
Author(s) -
Dan Frenkel,
Odelia Katz,
Beka Solomon
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.97.21.11455
Subject(s) - epitope , antibody , antigenicity , immunization , amyloid (mycology) , adjuvant , antigen , peptide , virology , p3 peptide , vaccination , active immunization , chemistry , phage display , biology , immunology , alzheimer's disease , medicine , biochemistry , amyloid precursor protein , disease , pathology , inorganic chemistry
The epitope EFRH, corresponding to amino acids 3–6 within the human β-amyloid peptide (AβP), acts as a regulatory site controlling both the formation and disaggregation process of the β-amyloid fibrils (Aβ). Locking of this epitope by highly specific antibodies affects the dynamics of the entire AβP molecule, preventing self-aggregation as well as enabling resolubilization of already formed aggregates. Production of such antibodies by repeated injections of toxic human Aβ 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 β-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 AβP identical to the human AβP 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.