Nonviral Aβ DNA vaccine therapy against Alzheimer's disease: Long-term effects and safety

摘要

It was recently demonstrated that amyloid β (Aβ) peptide vaccination was effective in reducing the Aβ burden in Alzheimer model mice. However, the clinical trial was halted because of the development of meningoencephalitis in some patients. To overcome this problem, anti-Aβ antibody therapy and other types of vaccination are now in trial. In this study, we have developed safe and effective nonviral Aβ DNA vaccines against Alzheimer's disease. We administered these vaccines to model (APP23) mice and evaluated Aβ burden reduction. Prophylactic treatments started before Aβ deposition reduced Aβ burden to 15.5% and 38.5% of that found in untreated mice at 7 and 18 months of age, respectively. Therapeutic treatment started after Aβ deposition reduced Aβ burden to ≈ 50% at the age of 18 months. Importantly, this therapy induced neither neuroinflammation nor T cell responses to Aβ peptide in both APP23 and wild-type B6 mice, even after long-term vaccination. Although it is reported that other anti-Aβ therapies have pharmacological and/or technical difficulties, nonviral DNA vaccines are highly secure and easily controllable and are promising for the treatment of Alzheimer's disease.