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

P-Amyloid (AD) peptide has been proposed to be a causal factor in Alzheimer's disease (AD). Currently being investigated, active and passive A beta-immunotherapy significantly reduce AD plaque deposition, neuritic dystrophy, and astrogliosis in the brains of APP transgenic (APP/Tg) mice. Immunization with A beta(42) formulated in the Th1-type adjuvant QS21 was beneficial for AD patients with significant titers of anti-A beta antibodies, however, 6% of participants developed meningoencephalitis, likely due to anti-A beta-specific autoimmune Th1 cells. Thus, successful AD 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 A beta(1-15) and foreign T cell epitopePADRE (PADRE-A beta(1-15)-MAP). Formulated in Quil A, this vaccine resulted in significantly higher anti-A beta antibody responses in both BALB/c (H-2(d)) and C57BL/6 (H-2(b)) mice, compared with Alum. Anti-A beta 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-AD 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-A beta antibody production was enhanced without changing the initially generated and likely beneficial Th2-type humoral response. (c) 2005 Elsevier Ltd. All rights reserved.