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

Vitaly Vasilevko; Viorela Pop; Hyun Jin Kim; Tommy Saing; Charles C. Glabe; Saskia Milton; Edward G. Barrett; Carl W. Cotman; David H. Cribbs; Elizabeth Head

Neurobiology of Disease (Sep 2010)

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

Vitaly Vasilevko,
Viorela Pop,
Hyun Jin Kim,
Tommy Saing,
Charles C. Glabe,
Saskia Milton,
Edward G. Barrett,
Carl W. Cotman,
David H. Cribbs,
Elizabeth Head

Affiliations

Vitaly Vasilevko: The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine 92697, USA; Corresponding author. University of California, Irvine, Institute for Memory Impairments and Neurological Disorders, 1207 Gillespie Neuroscience Research Facility, Irvine, CA 92697-4540, USA. Fax: +1 949 824 2071.
Viorela Pop: The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine 92697, USA; Department of Neurobiology and Behavior, University of California, Irvine 92697, USA
Hyun Jin Kim: The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine 92697, USA
Tommy Saing: The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine 92697, USA
Charles C. Glabe: Department of Molecular Biology and Biochemistry, University of California, Irvine 92697, USA
Saskia Milton: Department of Molecular Biology and Biochemistry, University of California, Irvine 92697, USA
Edward G. Barrett: Lovelace Respiratory Research Institute, Albuquerque, NM 87185, USA
Carl W. Cotman: The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine 92697, USA; Department of Neurology, University of California, Irvine 92697, USA
David H. Cribbs: The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine 92697, USA; Department of Neurology, University of California, Irvine 92697, USA
Elizabeth Head: The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine 92697, USA; Department of Neurology, University of California, Irvine 92697, USA

Journal volume & issue: Vol. 39, no. 3
pp. 301 – 310

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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