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

Abstract

Numerous pre-clinical studies and clinical trials demonstrated that induction of antibodies to the β-amyloid peptide of 42 residues (Aβ₄₂) elicits therapeutic effects in Alzheimer's disease (AD). However, an active vaccination strategy based on full length Aβ₄₂ 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 Aβ₄₂. 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-Aβ antibodies. Plasmid-based reverse genetics system was used for the rescue of recombinant influenza virus containing immunodominant B cell epitopes of Aβ₄₂ (Aβ_1-7/10). Two chimeric flu viruses expressing either 7 or 10 aa of Aβ₄₂ (flu-Aβ_1-7 or flu-Aβ_1-10) were generated and tested in mice as conventional inactivated vaccines. We demonstrated that this dual vaccine induced therapeutically potent anti-Aβ antibodies and anti-influenza antibodies in mice. 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.