Linear and conformation specific antibodies in aged beagles after prolonged vaccination with aggregated Abeta

NEUROBIOLOGY OF DISEASE

卷:39

Article

Vasilevko, Vitaly¹  Pop, Viorela²  Glabe, Charles C.³  Milton, Saskia³  Barrett, Edward G.⁵  Cotman, Carl W.⁴  Cribbs, David H.⁴  Head, Elizabeth⁴ 

[1] Univ Calif Irvine, Inst Memory Impairments & Neurol Disorders, Gillespie Neurosci Res Facil 1207, Irvine, CA 92697 USA

[2] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA

[3] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA

[4] Univ Calif Irvine, Dept Neurol, Irvine, CA 92697 USA

[5] Lovelace Resp Res Inst, Albuquerque, NM 87185 USA

关键词: Alzheimer's disease;    Immunotherapy;    Amyloid beta;    Large animal model;    Aged beagles;    Conformational antibodies;   

DOI  :  10.1016/j.nbd.2010.04.014

来源: Elsevier

【 摘 要 】

Previously we showed that anti-A beta, 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 2.4 years in canines immunized repeatedly with aggregated A beta(1-42) (AN1792) formulated in alum adjuvant. We observed a rapid and robust induction of anti-A beta, 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 A beta(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 A beta 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. (C) 2010 Elsevier Inc. All rights reserved.

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