Amyloid β3-10 DNA vaccination suggests a potential new treatment for Alzheimer's disease in BALB/c mice
摘要Background Amyloid β1-42 (Aβ42) peptide vaccination has been proved to be effective in reducing amyloid burden in brain and improving cognitive function in Alzheimer's disease (AD) mouse models.But the phase Ⅱ trial of Aβ42 peptide vaccine was halted because of T cell-mediated meningoencephalitis.In this study,a DNA vaccine,p(Aβ3-10)10-CpG,was constructed to test whether it would induce predominant TH2 immune response upon immunization of BALB/c mice.Methods BALB/c mice were vaccinated intramuscularly with p(Aβ3-10)10-CpG plasmids.Aβ42 peptide,pcDNA3.1(+)empty vector and PBS were injected to the control groups.Expression of interesting gene in injected muscle was identified by immunohistochemistry.Anti-Al3 antibody titers,isotype profiles as well as cytokines in ex vivo splenocytes culture supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA).Results P(Aβ3-10)10-CpG plasmid was expressed in muscle after injection detected by immunohistochemistry.The p(Aβ3-10)10-CpG vaccine induced high titers of anti-Aβ antibodies in BALB/c mice.And isotype of the antibodies was mainly IgG1,the IgG1/IgG2a ratio for the p(Aβ3-10)10-CpG group was approximately 5 times greater than that for the Aβ42 peptide group.Ex vivo cultured splenocytes isolated from mice immunized with p(Aβ3-10)10-CpG exhibited high interleukin-4 response and low interleukin-Y (IFN-Y) response.Conclusions Immunization with p(Aβ3-10)10-CpG vaccine primarily induces a TH2 type of response,thus reduces the probability of inflammation.This p(Aβ3-10)10-CpG vaccine possesses the basic factors required for a safe and effective AD vaccine.
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