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

Hayk Davtyan, Anahit Ghochikyan, Richard Cadagan, Dmitriy Zamarin, Irina Petrushina, Nina Movsesyan, Luis Martinez-Sobrido, Randy A. Albrecht, Adolfo García-Sastre, Michael G. Agadjanyan

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: 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.Methods: Plasmid-based reverse genetics system was used for the rescue of recombinant influenza virus containing immunodominant B cell epitopes of Aβ42 (Aβ1-7/10).Results: Two chimeric flu viruses expressing either 7 or 10 aa of Aβ42 (flu-Aβ1-7 or flu-Aβ1-10) 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.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.

Original languageEnglish
Article number127
JournalJournal of Translational Medicine
Volume9
Issue number1
DOIs
StatePublished - 1 Aug 2011

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