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

It was recently demonstrated that amyloid beta (A beta) peptide vaccination was effective in reducing the A beta 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-A beta antibody therapy and other types of vaccination are now in trial. In this study, we have developed safe and effective nonviral A beta DNA vaccines against Alzheimer's disease. We administered these vaccines to model (APP23) mice and evaluated A beta burden reduction. Prophylactic treatments started before A beta deposition reduced A beta 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 A beta deposition reduced A beta burden to approximate to 50% at the age of 18 months. Importantly, this therapy induced neither neuroinflammation nor T cell responses to All peptide in both APP23 and wild-type B6 mice, even after long-term vaccination. Although it is reported that other anti-A beta 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.