EFRH-phage immunization of Alzheimer's disease animal model improves behavioral performance in Morris water maze trials.
We have developed an immunization procedure for the production of effective anti-beta-amyloid (anti-Abeta) antibodies, using filamentous phage displaying only 4 amino acids. The EFRH sequence, encompassing amino acids 3-6 of the 42 residues of Abeta peptide, was found previously to be the main regulatory site for amyloid modulation and the epitope of anti-aggregating antibodies. Engineered filamentous phage enable the display of various numbers of EFRH copies on the phage and serve as potent carriers of antigens. In the present study we have found that phage displaying high EFRH copy number are effective in eliciting humoral response against the EFRH sequence, which in turn relieves the amyloid burden in the brains of amyloid precursor protein Tg mice and improves their ability to perform cognitive tasks.
Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv, Israel 69978.
Vered
V
Lavie
Maria
M
Becker
Rachel
R
Cohen-Kupiec
Iftach
I
Yacoby
Rela
R
Koppel
Manuela
M
Wedenig
Birgit
B
Hutter-Paier
Beka
B
Solomon
D000544:Alzheimer Disease / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D000595:Amino Acid Sequence / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001435:Bacteriophages / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D018628:Gene Dosage; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology*; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D000939:Epitopes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)