title: Amyloid β 3-10 DNA vaccination suggests a potential new treatment for Alzheimer's disease in BALB/c mice.
abstract: BACKGROUND
  Amyloid β(1-42) (Aβ(42)) 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 Aβ(42) peptide vaccine was halted because of T cell-mediated meningoencephalitis. In this study, a DNA vaccine, p(Aβ(3-10))(10)-CpG, was constructed to test whether it would induce predominant T(H)2 immune response upon immunization of BALB/c mice.
  
  
  METHODS
  BALB/c mice were vaccinated intramuscularly with p(Aβ(3-10))(10)-CpG plasmids. Aβ(42) 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-Aβ antibody titers, isotype profiles as well as cytokines in ex vivo splenocytes culture supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  P(Aβ(3-10))(10)-CpG plasmid was expressed in muscle after injection detected by immunohistochemistry. The p(Aβ(3-10))(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(Aβ(3-10))(10)-CpG group was approximately 5 times greater than that for the Aβ(42) peptide group. Ex vivo cultured splenocytes isolated from mice immunized with p(Aβ(3-10))(10)-CpG exhibited high interleukin-4 response and low interleukin-γ (IFN-γ) response.
  
  
  CONCLUSIONS
  Immunization with p(Aβ(3-10))(10)-CpG vaccine primarily induces a T(H)2 type of response, thus reduces the probability of inflammation. This p(Aβ(3-10))(10)-CpG vaccine possesses the basic factors required for a safe and effective AD vaccine.
authors: Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.
authors: Xiao-na
authors: XN
authors: Xing
authors: Wei-ge
authors: WG
authors: Zhang
authors: Sha
authors: S
authors: Sha
authors: Yu
authors: Y
authors: Li
authors: Rong
authors: R
authors: Guo
authors: Cai
authors: C
authors: Wang
authors: Yun-peng
authors: YP
authors: Cao
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D056724:Immunity, Humoral / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000627:therapeutic use*
chemical_list: D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D015847:Interleukin-4; D007371:Interferon-gamma