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

Abstract

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 Aβ1-43 and mouse IL-10 cDNA. Nasal but not intramuscular administration of the vaccine induced good antibody responses to Aβ. When APP transgenic mice (Tg2576) received this vaccine once nasally, the Aβ plaque burden was significantly decreased 8 weeks after without inducing inflammation in the brain. The amount of Aβ measured by ELISA was also reduced in both soluble and insoluble fractions of the brain homogenates, and notably the Aβ 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.