Adjuvant‐dependent modulation of Th1 and Th2 responses to immunization with β‐amyloid

The role of adjuvant on the Th1 and Th2 immune responses to Aβ-immunotherapy (Aβ42 peptide) was examined in wild-type mice. Fine epitope analysis with overlapping oligomers of the Aβ42 sequence identified the 1–15 region as a dominant B cell epitope. The 6–20 peptide was recognized only weakly by antisera from mice administrated with Aβ42 peptide formulated in complete Freund’s adjuvant (CFA), alum or TiterMax Gold (TMG). However, mice immunized with Aβ42 mixed with QS21 induced a significant antibody response to the 6–20 peptide. The only T cell epitope found was within the 6–28 sequence of Aβ42. QS21 and CFA induced the strongest humoral response to Aβ, alum was intermediate, and TMG the weakest adjuvant. Analysis of antibody isotypes specific for Aβ indicates that alum induces primarily Th2-type immune response, whereas TMG, CFA and QS21 shift the immune responses toward a Th1 phenotype. Stimulation of splenocytes from Aβ-immunized mice with Aβ40 peptide induced strikingly different cytokine expression profiles. QS21 and CFA induced significant IFN-γ, IL-4 and tumor necrosis factor-α expression, whereas alum induced primarily IL-4 production. As Th1-type immune responses have been implicated in many autoimmune disorders, whereas Th2-type responses have been shown to inhibit autoimmune disease, the choice of adjuvant may be critical for the design of a safe and effective immunotherapy for Alzheimer’s disease.