The immunological potency and therapeutic potential of a prototype dual vaccine against influenza and Alzheimer's disease.

ABSTRACT

BACKGROUND: Numerous pre-clinical studies and clinical trials demonstrated that induction of antibodies to the ß-amyloid peptide of 42 residues (Aß42) elicits therapeutic effects in Alzheimer's disease (AD). However, an active vaccination strategy based on full length Aß42 is currently hampered by elicitation of T cell pathological autoreactivity. We attempt to improve vaccine efficacy by creating a novel chimeric flu vaccine expressing the small immunodominant B cell epitope of Aß42. We hypothesized that in elderly people with pre-existing memory Th cells specific to influenza this dual vaccine will simultaneously boost anti-influenza immunity and induce production of therapeutically active anti-Aß antibodies. METHODS: Plasmid-based reverse genetics system was used for the rescue of recombinant influenza virus containing immunodominant B cell epitopes of Aß42 (Aß1-7/10). RESULTS: Two chimeric flu viruses expressing either 7 or 10 aa of Aß42 (flu-Aß1-7 or flu-Aß1-10) were generated and tested in mice as conventional inactivated vaccines. We demonstrated that this dual vaccine induced therapeutically potent anti-Aß antibodies and anti-influenza antibodies in mice. CONCLUSION: We suggest that this strategy might be beneficial for treatment of AD patients as well as for prevention of development of AD pathology in pre-symptomatic individuals while concurrently boosting immunity against influenza.