An Oral A beta Vaccine Using a Recombinant Adeno-Associated Virus Vector in Aged Monkeys: Reduction in Plaque Amyloid and Increase in A beta Oligomers

作者：Hara Hideo; Ono Fumiko; Nakamura Shinichiro; Matsumoto Shin ei; Jin Haifeng; Hattori Nobutaka; Tabira Takeshi^*

来源：Journal of Alzheimer's Disease, 2016, 54(3): 1047-1059.

DOI：10.3233/JAD-160514

• Adeno-associated virus vector
• Alzheimer's disease
• amyloid-beta
• A beta oligomer
• primate
• vaccine

With the objective to improve the amyloid-beta(A beta) targeting immunotherapy, we investigated the safety and efficacy of an oral vaccine with recombinant adeno-associated virus vector carrying a signal sequence and A beta(1-43) cDNA (rAAV/A beta) in old non-human primates, 12 African green and 10 cynomolgus monkeys. The enteric-dissolving coated capsules containing rAAV/A beta were orally administered once or twice, then monkeys' conditions were carefully observed with complete blood count and laboratory examinations of the sera. General conditions, food intake, water intake, stool conditions, body weight changes, and menstruation cycles were not significantly altered, and laboratory tests and pathological examinations of the systemic organs were unremarkable. Pathological examinations of the brain showed significant reduction of the amyloid plaque burden and intracellular A beta without inflammatory or hemorrhagic changes in the brain. However, soluble A beta and some A beta oligomers were increased in rAAV-treated monkey brains without changes of the neuronal density and vascular amyloidosis. Thus, this vaccine seems to be safe in general, but we must be cautious about the increase of A beta oligomers after vaccination. This vaccine may be recommended at a very early stage of Alzheimer's disease when little amyloid is deposited.

• 出版日期2016