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

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.

• Authors: Anahit Ghochikyan, Mikayel Mkrtichyan, Irina Petrushina, Nina Movsesyan, Adrine Karapetyan, David H Cribbs, Michael G Agadjanyan
• Journal: Vaccine (Vaccine) Vol. 24 Issue 13 Pg. 2275-82 (Mar 20 2006) ISSN: 0264-410X [Print] Netherlands
• PMID: 16368167 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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)