title: Generation and characterization of the humoral immune response to DNA immunization with a chimeric beta-amyloid-interleukin-4 minigene.
abstract: Active immunization with fibrillar beta-amyloid peptide (Abeta(42)) as well as passive transfer of anti-Abeta antibodies significantly reduces Abeta plaque deposition, neuritic dystrophy, and astrogliosis in the brain of mutant amyloid precursor protein (APP)-transgenic mice. Although the mechanism(s) of clearance of Abeta from the brain following active or passive immunization remains to be determined, it is clear that anti-Abeta antibodies are critical for clearance. DNA immunization provides an attractive alternative to direct peptide and adjuvant approaches for inducing a humoral response to Abeta. We constructed a DNA minigene with Abeta fused to mouse interleukin-4 (pAbeta(42)-IL-4) as a molecular adjuvant to generate anti-Abeta antibodies and enhance the Th2-type of immune responses. Gene gun immunizations induced primarily IgG1 and IgG2b anti-Abeta antibodies. Fine epitope analysis with overlapping peptides of the Abeta(42) sequence identified the 1-15 region as a dominant B cell epitope. The DNA minigene-induced anti-Abeta antibodies bound to Abeta plaques in brain tissue from an Alzheimer's disease patient demonstrating functional activity of the antibodies and the potential for therapeutic efficacy.
authors.affiliation: The Institute for Molecular Medicine, Department of Immunology, Huntington Beach, USA.
authors.forename: Anahit
authors.initials: A
authors.lastname: Ghochikyan
authors.forename: Vitaly
authors.initials: V
authors.lastname: Vasilevko
authors.forename: Irina
authors.initials: I
authors.lastname: Petrushina
authors.forename: Nina
authors.initials: N
authors.lastname: Movsesyan
authors.forename: Davit
authors.initials: D
authors.lastname: Babikyan
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Tian
authors.forename: Nadya
authors.initials: N
authors.lastname: Sadzikava
authors.forename: Ted M
authors.initials: TM
authors.lastname: Ross
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Head
authors.forename: David H
authors.initials: DH
authors.lastname: Cribbs
authors.forename: Michael G
authors.initials: MG
authors.lastname: Agadjanyan
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics / Q000276:immunology*; D000818:Animals; D019470:Biolistics; D016466:CHO Cells; D006224:Cricetinae; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte; D005260:Female; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000097:blood; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D018985:Epitopes, B-Lymphocyte; D007132:Immunoglobulin Isotypes; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D015847:Interleukin-4