Nasal mucosal inhalation of amyloid-beta peptide 3–10 defective adenovirus attenuates cytotoxicity induced by beta-amyloid (1–42)

Three-month-old Alzheimer's disease model transgenic mice were immunized with Aβ(1–42) Plp-Adenovirus [Ad]-X-CMV-(Aβ(3–10))(10)-CpG [AdCpG-(Aβ(3–10))(10)] or AdCpG virus fluid via nasal mucosal inhalation, respectively. ELISA analysis of serum showed Aβ(42) antibody titers were significantly increased in mice immunized with Aβ(1–42) and AdCpG-(Aβ(3–10))(10). Concanavalin A and AdCpG-(Aβ(3–10))(10) stimulation significantly increased the number of proliferating spleen cells cultured from AdCpG(Aβ(3–10))(10) and Aβ(42) groups compared with the control group. In the AdCpG(Aβ(3–10))(10) group, levels of interleukin (IL)-4 and IL-10 were increased, while those of IL-2 and interferon-γ were decreased. In the Aβ(42) group, levels of IL-4, IL-10, IL-2 and interferon-γ were all increased. Experimental findings indicate that AdCpG-(Aβ(3–10))(10) vaccine can produce strong T helper 2 (Th2) humoral immune responses in addition to the production of Aβ(42) antibody. The cellular immunologic response was weak and avoided Aβ(1–42)-mediated cytotoxicity.