Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Aβ antibody response with Alum to Quil A adjuvant switch

Anahit Ghochikyan, Mikayel Mkrtichyan, Irina Petrushina, Nina Movsesyan, Adrine Karapetyan, David H. Cribbs, Michael G. Agadjanyan

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

β-Amyloid (Aβ) peptide has been proposed to be a causal factor in Alzheimer's disease (AD). Currently being investigated, active and passive Aβ-immunotherapy significantly reduce Aβ plaque deposition, neuritic dystrophy, and astrogliosis in the brains of APP transgenic (APP/Tg) mice. Immunization with Aβ42 formulated in the Th1-type adjuvant QS21 was beneficial for AD patients with significant titers of anti-Aβ antibodies, however, 6% of participants developed meningoencephalitis, likely due to anti-Aβ-specific autoimmune Th1 cells. Thus, successful Aβ vaccination requires the development of strong antibody responses without Th1-type cellular immunity. In this study, we compared the induction of humoral immune responses with Th1-type (Quil A) and Th2-type (Alum) adjuvants singly and in combination, using our novel epitope vaccine composed of self B cell epitope Aβ1-15 and foreign T cell epitope PADRE (PADRE-Aβ 1-15-MAP). Formulated in Quil A, this vaccine resulted in significantly higher anti-Aβ antibody responses in both BALB/c (H-2 d) and C57BL/6 (H-2b) mice, compared with Alum. Anti-Aβ antibodies induced by Alum were predominantly IgG1 type accompanied by lower levels of IgG2a and IgG2b. Quil A induced robust and almost equal titers of anti-Aβ antibodies of IgG1 and IgG2a isotypes and slightly lower levels of IgG2b. Switching adjuvants from Alum to Quil A induced higher concentrations of antibodies than injections with Alum only, however slightly lower than Quil A only. Switching both adjuvants did not change the profile of antibody responses generated by the initial adjuvant injected. These results suggest that switching from Alum to Quil A would be beneficial for AD patients because anti-Aβ antibody production was enhanced without changing the initially generated and likely beneficial Th2-type humoral response.

Original languageEnglish (US)
Pages (from-to)2275-2282
Number of pages8
JournalVaccine
Volume24
Issue number13
DOIs
StatePublished - Mar 20 2006

Keywords

  • Alzheimer's disease (AD)
  • Epitope vaccine immunization
  • Th1 and Th2 adjuvants

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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    Ghochikyan, A., Mkrtichyan, M., Petrushina, I., Movsesyan, N., Karapetyan, A., Cribbs, D. H., & Agadjanyan, M. G. (2006). Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Aβ antibody response with Alum to Quil A adjuvant switch. Vaccine, 24(13), 2275-2282. https://doi.org/10.1016/j.vaccine.2005.11.039