P3-531: the rationale of mutated amyloid beta sensitized dendritic cells as a therapeutic vaccine for alzheimer's disease

Aging is considered as the most important risk factor for Alzheimer's disease, and the human body's immune system will decline with aging. There continues to be mounting evidence that proves that AD patients have an impaired immune system. Amyloid beta peptide aggregation is the known major pathological indicator and is associated to the impairment of the immune system. Many factors have been proposed to be the cause of AD. Following the single target approach in developing therapeutics for AD has had no success over many years. We believe that placing the immunotherapy target on Aβ will not only stop the progression of AD, this approach may prevent the development and onset of the disease. Since there is a strong T-cell epitope in wild type Aβ we have designed a mutant-peptide (CAO22W) to sensitize BMDCs to develop an effective, safe and immunomodulatory vaccine for Alzheimer's disease. The CAO22W mutant-peptide was designed and then synthesized (Biomer Tech Inc. CA, USA). We have treated the bone marrow derived dendritic cells with the peptide and deliver it into mice by either IP or IV to different age of APP/PS1 mice for up to 5 injections at bi-weekly intervals. The special working memory of the mice were tested for any benefit received. Antibody levels and cytokine profiles were analyzed for immunotype and the safety of the vaccine. This cell-based vaccine can induce Aβ specific antibody response without having the assistance of any adjuvant. The vaccine in some instances, can also stop or reverse spacial learning memory post-vaccination without alternating the immunomodulatory property of dendritic cell compared to the DC only group (p<0.01). The mutant-peptide sensitized dendritic cell can break the immunotolerance associated to Aβ and can enhance the both humoral and cellular immunity. The mutant peptide named CAO22W can effectively sensitized dendritic cells. We have successfully developed a therapeutic AD vaccine by having tested the preparation on several different amyloid mouse models. This T-cell epitope mutation overcomes the potential autoimmune response triggered by wild-type amyloid peptide and can also strengthen the immune system without having any adverse effects.