Polymer-Encapsulated Aβ Peptide Fragments as an Oligomeric-Specific Vaccine for Alzheimer's Disease.

Vaccination is regarded as one of the most cost-effective and reliable methods for combating disease. We have developed a new method for an oligomeric Aβ-specific AD vaccination using polymer micelle-encapsulated peptide fragments, which overcome many problems of vaccination associated with the direct use of the Aβ1–42 peptide. We studied different encapsulated forms of shortened Aβ peptides with and without the entire T cell epitope in an APP/PS1 mouse model. After two inoculations with encapsulated Aβ fragments, antibodies were produced in all mice with antibody titer greater than 1:12,800. No anti-polymer antibodies were detected after five inoculations, and none of the injected mice showed any adverse effects throughout experimentation. Anti-Aβ antibodies from our polymer-encapsulated vaccine were able to bind to A plaques in the brain of our mice, and were able to specifically recognize oligomeric Aβ. Our results suggest that the safety and efficacy issues previously encountered in other Aβ vaccination trials may be successfully addressed by using micelle-encapsulated peptides. These shorter Aβ fragments are also easier to synthesize and more cost-effective than the highly hydrophobic full-length Aβ1–42 peptide.