title: Dendrimeric Abeta1-15 is an effective immunogen in wildtype and APP-tg mice.
abstract: Immunization of humans and APP-tg mice with full-length beta-amyloid (Abeta) results in reduced cerebral Abeta levels. However, due to adverse events in the AN1792 trial, alternative vaccines are required. We investigated dendrimeric Abeta1-15 (dAbeta1-15), which is composed of 16 copies of Abeta1-15 peptide on a branched lysine core and thus, includes an Abeta-specific B cell epitope but lacks the reported T cell epitope. Immunization by subcutaneous, transcutaneous, and intranasal routes of B6D2F1 wildtype mice led to anti-Abeta antibody production. Antibody isotypes were mainly IgG1 for subcutaneous or transcutaneous immunization and IgG2b for intranasal immunization, suggestive of a Th2-biased response. All Abeta antibodies preferentially recognized an epitope in Abeta1-7. Intranasal immunization of J20 APP-tg mice resulted in a robust humoral immune response with a corresponding significant reduction in cerebral plaque burden. Splenocyte proliferation against Abeta peptide was minimal indicating the lack of an Abeta-specific cellular immune response. Anti-Abeta antibodies bound monomeric, oligomeric, and fibrillar Abeta. Our data suggest that dAbeta1-15 may be an effective and potentially safer immunogen for Alzheimer's disease (AD) vaccination.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Seabrook
authors.forename: Katelyn
authors.initials: K
authors.lastname: Thomas
authors.forename: Liying
authors.initials: L
authors.lastname: Jiang
authors.forename: Jeanne
authors.initials: J
authors.lastname: Bloom
authors.forename: Edward
authors.initials: E
authors.lastname: Spooner
authors.forename: Marcel
authors.initials: M
authors.lastname: Maier
authors.forename: Gal
authors.initials: G
authors.lastname: Bitan
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Lemere
mesh_terms: D000279:Administration, Cutaneous; D000281:Administration, Intranasal; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000097:blood; D000918:Antibody Specificity; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D029968:Escherichia coli Proteins / Q000276:immunology; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: C437846:AN-1792; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D016207:Cytokines; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; D010446:Peptide Fragments; D014612:Vaccines; C480626:amyloid beta-protein (1-15)