Combination of gene delivery and DNA vaccination to protect from and reverse Th1 autoimmune disease via deviation to the Th2 pathway

Immunity. 2001 Jul;15(1):15-22. doi: 10.1016/s1074-7613(01)00171-6.


Using a combination of local gene delivery and tolerizing DNA vaccination, we demonstrate that codelivery of the interleukin-4 (IL-4) gene and a DNA vaccine encoding the self-peptide proteolipid protein 139-151 (PLP139-151) provides protective immunity against experimental autoimmune encephalomyelitis (EAE). We provide evidence for a mechanism whereby IL-4 expressed from the naked DNA is secreted and acts locally on autoreactive T cells via activation of STAT6 to shift their cytokine profile to T helper 2. We also show that DNA vaccines can be used to reverse established EAE by covaccination with the genes for myelin oligodendrocyte glycoprotein and IL-4. This treatment strategy combines the antigen-specific effects of DNA vaccination and the beneficial effects of local gene delivery.

Publication types

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

MeSH terms

  • Animals
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Female
  • Genetic Therapy*
  • Humans
  • Interleukin-4 / genetics*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • STAT6 Transcription Factor
  • Th1 Cells / physiology*
  • Th2 Cells / physiology*
  • Trans-Activators / metabolism
  • Vaccination
  • Vaccines, DNA / immunology*


  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Stat6 protein, mouse
  • Trans-Activators
  • Vaccines, DNA
  • Interleukin-4