Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase

Diabetologia. 2002 May;45(5):668-76. doi: 10.1007/s00125-002-0806-9. Epub 2002 Apr 4.


Aims/hypotheses: Type I (insulin-dependent) diabetes mellitus results from T-cell-mediated autoimmune destruction of pancreatic beta cells. Among the beta-cell autoantigens that have been implicated in triggering of beta-cell-specific autoimmunity, glutamic acid decarboxylase (GAD) is a strong candidate in both humans and the NOD mouse. We aimed to determine whether treatment with a recombinant vaccinia virus expressing GAD (rVV-GAD65) could prevent the development of diabetes in NOD mice.

Methods: Three-eight-to-nine-week-old female NOD mice were injected with various doses of rVV-GAD65 or rVV-MJ601as a control. We then examined the incidence of diabetes, T-cell proliferative response to GAD, amounts of anti-GAD IgGs, cytokine production and generation of regulatory cell populations.

Results: Administration of rVV-GAD65 to NOD mice prevented diabetes in an age-dependent and dose-dependent manner. Splenic T cells from rVV-GAD65-treated mice did not proliferate in response to GAD65. The amount of IgG1 was increased, whereas IgG2a amounts did not change in rVV-GAD65-treated NOD mice. The production of interleukin-4 increased, whereas the production of interferon-gamma decreased in rVV-GAD65-treated mice after stimulation with GAD. Furthermore, splenocytes from rVV-GAD65-treated NOD mice prevented the transfer of diabetes by splenocytes from acutely diabetic NOD mice in NOD. scid recipients.

Conclusion/interpretation: Immunogene therapy using a recombinant vaccinia virus expressing GAD results in the prevention of autoimmune diabetes in NOD mice by the induction of immunological tolerance through active suppression of effector T cells, and this treatment might have therapeutic value for the prevention of Type I diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer / methods*
  • Animals
  • Base Sequence
  • DNA Primers
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Female
  • Genetic Therapy*
  • Genetic Vectors
  • Glutamate Decarboxylase / immunology*
  • Hypoxanthine Phosphoribosyltransferase / genetics
  • Isoenzymes / immunology*
  • Lymphocytes / immunology
  • Mice
  • Mice, Inbred NOD
  • Recombination, Genetic
  • Spleen / immunology
  • Vaccines, DNA / therapeutic use*
  • Vaccinia virus


  • DNA Primers
  • Isoenzymes
  • Vaccines, DNA
  • Hypoxanthine Phosphoribosyltransferase
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2