[P2–056]: AN IMMUNOMODULATORY VACCINE AGAINST Aβ FOR ALZHEIMER's DISEASE

Despite 110 years of discovery, no effective treatment approach for AD exists. This is largely because therapeutics developed in the past, including the current failed clinical trial of Solanezumab, have never targeted the impaired immune system. Additionally, all FDA approved drugs address only the symptoms and have nothing to do with the cause of AD. Furthermore, none of FDA approved medication has long term efficacy. Moreover, AD patients must use drugs for the rest of their life once diagnosed with AD. Recent developments in treatment have primarily favored both active and passive immunotherapy since they target on the pathological molecules and can slow down the progress of AD effectively. However, they could not repair the impaired immune system, so their efficacy is very limited. Bone marrow were isolated from the littermate of our transgenic mice colony, and derived into dendritic cells using IL4 plus GM-CSF. DCs then were stimulated with mutant Aβ peptide or wild Aβ peptide at 20 μg/ml for 4 days and then injected into memory impaired APP/PS1 mice for upto 5 injections. Blood was collected by submandibular vein punctuation, then anti-Aβ antibody titer was detected using ELISA. Radial arm water maze was used to evaluate the learning memory before and post treatment. Flow cytometry and Luminex assay were used to monitor the immune system. Brain pathological and biochemical assay were used to identify changes in brain post treatment. Antibody production was detected only in the mutant peptide group by ELISA after two injections, and then continuous detected after each injection. Radial arm water maze test proved the memory (error and latency) improved only in mice received the mutant peptide sensitized dendritic cell. Also, the mutant peptide group has the similar immunomodulatory profile as the dendritic cell injected group. No any adverse effects have been observed in the study. Our mutant peptide sensitized vaccine is a safe and effective vaccine for AD treatment. This vaccine is proper for AD patient, because it can reactive the immune system and target on the pathological factor. This vaccine is matured and ready for clinical use.