Assessment of Non-Viral Amyloid-β DNA Vaccines on Amyloid-β Reduction and Safety in Rhesus Monkeys

Abstract

We recently demonstrated that newly developed non-viral amyloid-β (Aβ) DNA vaccines are safe and effective in reducing Aβ burdens in the brains of Alzheimer's disease (AD) model mice. The present study was undertaken to examine whether DNA vaccines effectively and safely reduce Aβ deposition in the brain of rhesus monkeys. For this purpose, DNA vaccines or empty vector at a dose of 3 mg were injected intramuscularly on a biweekly basis into rhesus monkeys (15-18 years old). Before and during vaccination, blood was drawn once a month and used for hematological and biochemical examinations. Six months after the first vaccination, it was demonstrated that anti-Aβ antibodies in plasma of vaccinated monkeys were significantly elevated than that of control monkeys. Immunohistochemical examinations revealed that DNA vaccination reduced the Aβ burden to approximately 50% of that found in control monkeys (p=0.026). There was neither inflammation nor microhemorrhage in the brain and no significant changes in cytokine and chemokine levels in the blood throughout the observation period. Taken together, DNA vaccination to monkeys is safe and effective in Aβ reduction and provides useful information for performing preclinical and clinical trials.