کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9645121 1433683 2005 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
HSV amplicon-mediated Aβ vaccination in Tg2576 mice: differential antigen-specific immune responses
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
HSV amplicon-mediated Aβ vaccination in Tg2576 mice: differential antigen-specific immune responses
چکیده انگلیسی
Given the participation of amyloid beta (Aβ) in Alzheimer's disease (AD) pathogenesis the derivation of experimental therapeutics to prevent Aβ fibrillogenesis and/or enhance removal of parenchymal amyloid deposits represent viable disease-modifying approaches. Active Aβ-based immunotherapies have shown promise in mouse AD models, but application in human trials was accompanied by moderate brain inflammation in a subset of patients. Immune-shaping vaccine platforms may mitigate adverse effects. Herein, we describe the use of herpes simplex virus (HSV)-derived amplicons to elicit distinctive immune responses against Aβ. Two vaccine vectors were constructed: one expressing Aβ1-42 alone (HSVAβ), and a second expressing Aβ1-42 fused with the molecular adjuvant tetanus toxin Fragment C (HSVAβ/TtxFC). Peripheral administration of these vaccines augmented humoral responses to Aβ and reduced CNS Aβ deposition in Tg2576 AD mice. Interestingly and unexpectedly, HSVAβ vaccination was uniquely toxic and incited the expression of pro-inflammatory molecule transcripts within the hippocampi of Tg2576 mice, suggesting that this paradigm may serve as a relevant model to study Aβ vaccine-elicited CNS inflammatory syndromes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 26, Issue 4, April 2005, Pages 393-407
نویسندگان
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