Comparison of HPV DNA vaccines employing intracellular targeting strategies

Gene Ther. 2004 Jun;11(12):1011-8. doi: 10.1038/


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. In the context of DNA vaccines, we previously used the gene gun approach to test several intracellular targeting strategies that are able to route a model antigen, such as the human papillomavirus type-16 (HPV-16) E7, to desired subcellular compartments in order to enhance antigen processing and presentation to T cells. These strategies include the use of the sorting signal of lysosome-associated membrane protein (LAMP-1), Mycobacterium tuberculosis heat-shock protein 70 (HSP70), calreticulin (CRT) and the translocation domain (dII) of Pseudomonas aeruginosa exotoxin A (ETA). Vaccination with DNA vaccines encoding E7 antigen linked to any of these molecules all led to a significant enhancement of E7-specific CD8(+) T-cell immune responses and strong antitumor effects against an E7-expressing tumor, TC-1. However, we were interested in identifying the most potent DNA vaccine for our future clinical trials. Thus, we performed a series of experiments to directly compare the potency of the various DNA vaccines. Among the DNA vaccines we tested, we found that vaccination with pcDNA3-CRT/E7 generated the highest number of E7-specific CD8(+) T cells and potent long-term protection and treatment effects against E7-expressing tumors in mice. Interestingly, we observed that pcDNA3-CRT/E7 is also capable of protecting against an E7-expressing tumor with downregulated MHC class I expression, a common feature associated with most HPV-associated cervical cancers. Our data suggest that the DNA vaccine linking CRT to E7 (CRT/E7) may be a suitable candidate for human trials for the control of HPV infections and HPV-associated lesions.

Publication types

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

MeSH terms

  • Animals
  • Biolistics
  • CD8-Positive T-Lymphocytes / immunology*
  • Calreticulin / genetics
  • Cell Line, Tumor
  • Female
  • Gene Targeting
  • Genetic Therapy / methods*
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Oncogene Proteins, Viral / genetics*
  • Papillomaviridae / genetics*
  • Papillomaviridae / immunology*
  • Papillomavirus E7 Proteins
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / therapy*
  • Recombinant Proteins / administration & dosage
  • Skin / immunology*
  • Vaccines, DNA / administration & dosage*


  • Calreticulin
  • Histocompatibility Antigens Class I
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Recombinant Proteins
  • Vaccines, DNA
  • oncogene protein E7, Human papillomavirus type 16