4.5 Article

Mucosal immunotherapy in an Alzheimer mouse model by recombinant Sendai virus vector carrying Aβ1-43/IL-10 cDNA

Journal

VACCINE
Volume 29, Issue 43, Pages 7474-7482

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2011.07.057

Keywords

Alzheimer's disease; Immunotherapy; Sendaivirus vector; Amyloid

Funding

  1. Ministry of Education, Culture, Sports, Science and Technology of Japan [NIBIO 05-27]
  2. The Meijo Asian Res. Center
  3. Grant-in-Aid for Explor. Res.
  4. Grant-in-Aid for Scientific Res.
  5. JSPS
  6. Grants-in-Aid for Scientific Research [21390364] Funding Source: KAKEN

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Based on the amyloid cascade hypothesis, many reports have indicated that immunotherapy is beneficial for Alzheimer's disease (AD). We developed a mucosal immunotherapy for AD by nasal administration of recombinant Sendai virus vector carrying A beta 1-43 and mouse IL-10 cDNA. Nasal but not intramuscular administration of the vaccine induced good antibody responses to A beta. When APP transgenic mice (Tg2576) received this vaccine once nasally, the A beta plaque burden was significantly decreased 8 weeks after without inducing inflammation in the brain. The amount of A beta measured by ELISA was also reduced in both soluble and insoluble fractions of the brain homogenates, and notably the A beta oligomer (12-mer) was also apparently decreased. Tg2576 mice showed significant improvement in cognitive functions examined at 3 months after vaccination. Thus, this is an alternative immunotherapy for AD, which has an advantage in non-invasive, safe and relatively long lasting features. (C) 2011 Elsevier Ltd. All rights reserved.

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