[Mucosal immunotherapy for alzheimer's disease with viral vectors].
Alzheimer's disease is characterized by progressive loss of cognitive function due to amyloid-l (Al) 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 Al 1-43/IL-10. Oral or nasal administration of recombinant virus vector induced the long-term expression of All in the epithelial cells and presented the Ap antigen to the mucosal immune system. Antibody levels in the mouse serum were elevated after 4 weeks and the antibody inhibited the aggregation of Ap in vitro. Immunohistochemistry of the APP transgenic mouse brain tissue showed that All 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 Ap depositions without inflammation and reduced the levels of Al in the brain homogenates of APP transgenic mice; therefore, it might be effective for the treatment of Alzheimer's disease.
Hara
Hideo
H
Department of Vascular Dementia Research, NILS, National Center for Geriatrics and Gerontology, Japan. hihara@fujita-hu.ac.jp
Inoue
Makoto
M
Adachi
Kayo
K
Yonemitsu
Yoshikazu
Y
Hasegawa
Mamoru
M
Nabeshima
Toshitaka
T
Tabira
Takeshi
T
D000544:Alzheimer Disease / Q000517:prevention & control / Q000628:therapy*; D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D005822:Genetic Vectors; D006801:Humans; D007110:Immunity, Active; D007116:Immunization, Passive; D007167:Immunotherapy; D051379:Mice; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000276:immunology
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal