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Nasal inoculation of an adenovirus vector encoding 11 tandem repeats of Aβ1‐6 upregulates IL‐10 expression and reduces amyloid load in a Mo/Hu APPswe PS1dE9 mouse model of Alzheimer's disease
Author(s) -
Kim HongDuck,
Tahara Kazuki,
Maxwell J. Adam,
Lalonde Robert,
Fukuiwa Tatsuya,
Fujihashi Kohtaro,
Van Kampen Kent R.,
Kong FanKun,
Tang Dechu C.,
Fukuchi Kenichiro
Publication year - 2007
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.993
Subject(s) - downregulation and upregulation , immunology , immunization , immune system , senile plaques , viral vector , biology , alzheimer's disease , medicine , recombinant dna , pathology , disease , biochemistry , gene
Background One of the pathological hallmarks of Alzheimer's disease (AD) is deposits of amyloid β‐peptide (Aβ) in neuritic plaques and cerebral vessels. Immunization of AD mouse models with Aβ reduces Aβ deposits and improves memory and learning deficits. Because recent clinical trials of immunization with Aβ were halted due to brain inflammation that was presumably induced by a T‐cell‐mediated autoimmune response, vaccination modalities that elicit predominantly humoral immune responses are currently being developed. Methods We have nasally immunized a young AD mouse model with an adenovirus vector encoding 11 tandem repeats of Aβ1‐6 fused to the receptor‐binding domain (Ia) of Pseudomonas exotoxin A (PEDI), AdPEDI‐(Aβ1‐6) 11 , in order to evaluate the efficacy of the vector in preventing Aβ deposits in the brain. We also have investigated immune responses of mice to AdPEDI‐(Aβ1‐6) 11 . Results Nasal immunization of an AD mouse model with AdPEDI‐(Aβ1‐6) 11 elicited a predominant IgG1 response and reduced Aβ load in the brain. The plasma IL‐10 level in the AD mouse model was upregulated after immunization and, upon the stimulation with PEDI‐(Aβ1‐6) 11 , marked IL‐10 responses were found in splenic CD4 + T cells from C57BL/6 mice that had been immunized with AdPEDI‐(Aβ1‐6) 11 . Conclusions These results suggest that the induction of Th2‐biased responses with AdPEDI‐(Aβ1‐6) 11 in mice is mediated in part through the upregulation of IL‐10, which inhibits activation of dendritic cells that dictate the induction of Th1 cells. Copyright © 2007 John Wiley & Sons, Ltd.