Vaccination of Alzheimer's model mice with adenovirus vector containing quadrivalent foldable A beta(1-15) reduces A beta burden and behavioral impairment without A beta-specific T cell response
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AbstractActive amyloid beta (A beta) vaccination has been shown to be effective in clearing cerebral A beta and improving cognitive function in mouse models of Alzheimer's disease (AD). The meningoencephalitis observed in AD vaccination trial was likely related to excessive T cell-mediated immunity caused by the immunogen A beta(1-42). To avoid this toxicity, previous researchers have been using synthetic truncated A beta derivatives that promote humoral immunity. In this study, we develop a novel adenovirus vaccine, which can express quadrivalent foldable A beta(1-15) (4xA beta(15)) and gene adjuvant GM-CSF in vivo. Importantly, the 4xA beta(15) sequence includes an A beta-specific B cell epitope but lacks the reported T cell epitope. The 4xA beta(15) adenovirus vaccine induces an A beta-specific IgGl predominant humoral immune response, and reduces brain A deposition and cognition deficits in Tg2576 mice. Detection of IL-4 and IFN-gamma in restimulated splenocytes shows a significant Th2-polarized immune response. Stimulation of splenocytes with 4xA beta(15) peptides results in robust proliferative responses, whereas proliferation is absent after stimulation with full-length A beta, which indicates that the 4xA beta(15) adenovirus vaccine does not induce A beta-specific T cellular immune response. Thus, our results raise the possibility that adenovirus vector encoding 4xA beta(15) would be a promising candidate for future AD vaccination program. (C) 2008 Elsevier B.V. All rights reserved.
All Author(s) ListZou JT, Yao ZB, Zhang G, Wang HQ, Xu J, Yew DT, Forster EL
Journal nameJournal of the Neurological Sciences
Volume Number272
Issue Number1-2
Pages87 - 98
LanguagesEnglish-United Kingdom
KeywordsAlzheimer's disease; immunotherapy; multivalent adenovirus vaccine; T cell immune response; transgenic mice
Web of Science Subject CategoriesClinical Neurology; CLINICAL NEUROLOGY; Neurosciences; NEUROSCIENCES; Neurosciences & Neurology

Last updated on 2020-25-01 at 00:40