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

Vaccine. 2006 Mar 20;24(13):2275-82. doi: 10.1016/j.vaccine.2005.11.039. Epub 2005 Dec 5.

Abstract

Beta-amyloid (Abeta) peptide has been proposed to be a causal factor in Alzheimer's disease (AD). Currently being investigated, active and passive Abeta-immunotherapy significantly reduce Abeta plaque deposition, neuritic dystrophy, and astrogliosis in the brains of APP transgenic (APP/Tg) mice. Immunization with Abeta42 formulated in the Th1-type adjuvant QS21 was beneficial for AD patients with significant titers of anti-Abeta antibodies, however, 6% of participants developed meningoencephalitis, likely due to anti-Abeta-specific autoimmune Th1 cells. Thus, successful Abeta 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 Abeta(1-15) and foreign T cell epitope PADRE (PADRE-Abeta(1-15)-MAP). Formulated in Quil A, this vaccine resulted in significantly higher anti-Abeta antibody responses in both BALB/c (H-2d) and C57BL/6 (H-2b) mice, compared with Alum. Anti-Abeta 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-Abeta 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-Abeta antibody production was enhanced without changing the initially generated and likely beneficial Th2-type humoral response.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Alum Compounds / administration & dosage*
  • Alzheimer Disease / prevention & control*
  • Amyloid beta-Peptides / immunology*
  • Animals
  • Antibody Formation
  • Brain / pathology
  • Epitopes, B-Lymphocyte*
  • Epitopes, T-Lymphocyte*
  • Female
  • Immunization
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Quillaja Saponins
  • Saponins / administration & dosage*
  • Th1 Cells / immunology
  • Th2 Cells / immunology*

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Amyloid beta-Peptides
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Quillaja Saponins
  • Saponins
  • aluminum sulfate
  • Quil A