title: 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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, USA. magadjanyan@immed.org
authors.forename: Hayk
authors.initials: H
authors.lastname: Davtyan
authors.forename: Anahit
authors.initials: A
authors.lastname: Ghochikyan
authors.forename: Richard
authors.initials: R
authors.lastname: Cadagan
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Zamarin
authors.forename: Irina
authors.initials: I
authors.lastname: Petrushina
authors.forename: Nina
authors.initials: N
authors.lastname: Movsesyan
authors.forename: Luis
authors.initials: L
authors.lastname: Martinez-Sobrido
authors.forename: Randy A
authors.initials: RA
authors.lastname: Albrecht
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Michael G
authors.initials: MG
authors.lastname: Agadjanyan
mesh_terms: D000371:Agglutination; D000544:Alzheimer Disease / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D007114:Immunization; D007252:Influenza Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology
chemical_list: D016229:Amyloid beta-Peptides; D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D007252:Influenza Vaccines