Linear and conformation specific antibodies in aged beagles after prolonged vaccination with aggregated Abeta.
Previously we showed that anti-Abeta peptide immunotherapy significantly attenuated Alzheimer's-like amyloid deposition in the central nervous system of aged canines. In this report we have characterized the changes that occurred in the humoral immune response over 2.4years in canines immunized repeatedly with aggregated Abeta(1-42) (AN1792) formulated in alum adjuvant. We observed a rapid and robust induction of anti-Abeta antibody titers, which were associated with an anti-inflammatory T helper type 2 (Th2) response. The initial antibody response was against dominant linear epitope at the N-terminus region of the Abeta(1-42) peptide, which is identical to the one in humans and vervet monkeys. After multiple immunizations the antibody response drifted toward the elevation of antibodies that recognized conformational epitopes of assembled forms of Abeta and other types of amyloid. Our findings indicate that prolonged immunization results in distinctive temporal changes in antibody profiles, which may be important for other experimental and clinical settings.
Vasilevko
Vitaly
V
The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine 92697-4540, USA. vvasilev@uci.edu
Pop
Viorela
V
Kim
Hyun Jin
HJ
Saing
Tommy
T
Glabe
Charles C
CC
Milton
Saskia
S
Barrett
Edward G
EG
Cotman
Carl W
CW
Cribbs
David H
DH
Head
Elizabeth
E
D000544:Alzheimer Disease / Q000276:immunology / Q000517:prevention & control; D023582:Alzheimer Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D015153:Blotting, Western; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D008137:Longitudinal Studies; D014611:Vaccination
C437846:AN-1792; D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D000939:Epitopes
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