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

Neurobiology of Disease

Viorela Pop¹  Tommy Saing²  Edward G. Barrett³  Carl W. Cotman³  David H. Cribbs⁴  Hyun Jin Kim⁵  Saskia Milton⁵  Vitaly Vasilevko⁵  Elizabeth Head⁵  Charles C. Glabe⁵ 

[1] Corresponding author. University of California, Irvine, Institute for Memory Impairments and Neurological Disorders, 1207 Gillespie Neuroscience Research Facility, Irvine, CA 92697-4540, USA. Fax: [phone].;Department of Neurobiology and Behavior, University of California, Irvine 92697, USA;Department of Molecular Biology and Biochemistry, University of California, Irvine 92697, USA;Lovelace Respiratory Research Institute, Albuquerque, NM 87185, USA;The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine 92697, USA;

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

DOI  :  

来源: DOAJ

【 摘 要 】

Previously we showed that anti-Aβ 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 Aβ1–42 (AN1792) formulated in alum adjuvant. We observed a rapid and robust induction of anti-Aβ 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 Aβ1–42 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 Aβ 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.

【 授权许可】

Unknown