Intradermal administration of DNA vaccines combining a strategy to bypass antigen processing with a strategy to prolong dendritic cell survival enhances DNA vaccine potency

Vaccine. 2007 Nov 7;25(45):7824-31. doi: 10.1016/j.vaccine.2007.08.036. Epub 2007 Sep 4.


Intradermal vaccination via gene gun efficiently delivers DNA vaccines into dendritic cells (DCs) of the skin, resulting in the activation and priming of antigen-specific T cells in vivo. We have previously demonstrated that intradermal delivery of DNA vaccines encoding single-chain trimer (SCT) composed of the most immunogenic epitope of human papillomavirus type 16 (HPV-16) E6 protein (aa49-57), beta2-microglobulin, and MHC class I heavy chain (SCT-E6) can bypass antigen processing and lead to stable cell-surface presentation of E6 peptides. We also showed that co-administration of DNA vaccines with DNA encoding anti-apoptotic proteins can prolong the survival of DNA-transduced DCs, resulting in significant enhancement of antigen-specific CD8(+) T cell immune responses. In the current study, we hypothesized that combining the SCT strategy and antiapoptotic strategy may further enhance DNA vaccine potency by augmenting antigen-specific CD8(+) T cell immune responses and antitumor effects in vaccinated mice. Here, we show that C57BL/6 mice vaccinated with SCT-E6 DNA combined with antiapoptotic protein Bcl-xL DNA generated enhanced E6-specific CD8(+) T cell immune responses compared to mice vaccinated with SCT-E6 DNA and a non-functional mutant Bcl-xL (mtBcl-xL) DNA. Furthermore, we show that mice treated with SCT-E6 and Bcl-xL DNA generated enhanced anti-tumor effects against E6-expressing tumor cells (TC-1/Luciferase) compared to mice treated with SCT-E6 and mtBcl-xL DNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Survival
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / physiology
  • Drug Administration Routes*
  • Epitopes / genetics
  • Epitopes / immunology
  • Injections, Intradermal
  • Mice
  • Mice, Inbred C57BL
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology
  • Papillomaviridae / genetics
  • Papillomaviridae / immunology*
  • Papillomavirus Vaccines / administration & dosage
  • Papillomavirus Vaccines / immunology
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / immunology


  • E6 protein, Human papillomavirus type 16
  • Epitopes
  • Oncogene Proteins, Viral
  • Papillomavirus Vaccines
  • Repressor Proteins
  • Vaccines, DNA