Mucosal immunotherapy for Alzheimer's disease with viral vectors

Alzheimer's disease is characterized by progressive loss of cognitive function due to amyloid-β (Aβ) deposits in the central nervous system. Based on the amyloid cascade theory, many reports indicated that immunotherapy is effective for the treatment of Alzheimer's disease. We developed a mucosal immunotherapy for Alzheimer's disease via oral vaccine with recombinant adeno-associated virus (AAV) vector and nasal administration of recombinant sendaivirus vector expressing Aβ 1-43/IL-10. Oral or nasal administration of recombinant virus vector induced the long-term expression of Aβ in the epithelial cells and presented the Aβ antigen to the mucosal immune system. Antibody levels in the mouse serum were elevated after 4 weeks and the antibody inhibited the aggregation of Aβ in vitro. Immunohistochemistry of the APP transgenic mouse brain tissue showed that Aβ burdens were markedly decreased in the treated mouse compared to the control. The inflammation was not recognized in any organ including brain and kidney. Mucosal immunotherapy with viral vectors significantly cleared the Aβ depositions without inflammation and reduced the levels of Aβ in the brain homogenates of APP transgenic mice; therefore, it might be effective for the treatment of Alzheimer's disease.