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

J Transl Med. 2011 Aug 1;9:127. doi: 10.1186/1479-5876-9-127.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agglutination
  • Alzheimer Disease / immunology*
  • Amyloid beta-Peptides / immunology
  • Animals
  • Antibodies, Viral / immunology
  • Antibody Formation / immunology
  • Antibody Specificity / immunology
  • Epitopes, B-Lymphocyte / immunology
  • Female
  • Humans
  • Immunity, Humoral / immunology
  • Immunization
  • Influenza Vaccines / immunology*
  • Influenza Vaccines / therapeutic use*
  • Influenza, Human / immunology*
  • Influenza, Human / virology
  • Kinetics
  • Mice
  • Mice, Inbred C57BL
  • Neutralization Tests
  • Orthomyxoviridae / immunology
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / virology

Substances

  • Amyloid beta-Peptides
  • Antibodies, Viral
  • Epitopes, B-Lymphocyte
  • Influenza Vaccines