Enhancement of protein vaccine potency by in vivo electroporation mediated intramuscular injection

Vaccine. 2011 Jan 29;29(5):1082-9. doi: 10.1016/j.vaccine.2010.11.063. Epub 2010 Dec 4.

Abstract

Protein-based vaccines have emerged as a potentially promising approach for the generation of antigen-specific immune responses. However, due to their low immunogenicity, there is a need for innovative approaches to enhance protein-based vaccine potency. One approach to enhance protein-based vaccine potency is the employment of toll-like receptor ligands, such as CpG oligonucleotides, to activate the antigen-specific T cell immune responses. Another approach involves employing a method capable of improving the delivery of protein-based vaccine intramuscularly to lead to the slow release of the protein, resulting in improved vaccine potency. In the current study, we aimed to determine whether intramuscular injection of protein-based vaccines in conjunction with CpG followed by electroporation can lead to increased delivery of the protein-based vaccine into muscle cells, resulting in enhanced protein-based vaccine potency. We found that intramuscular injection followed by electroporation can effectively transduce the protein-based vaccine into the muscle cells. Furthermore, we found that intramuscular vaccination with OVA protein in combination with CpG followed by electroporation generates the best OVA-specific CD8+ T cell immune responses as well as the best protective and therapeutic antitumor effects in vaccinated mice. CD8+ T cells were found to play an important role in the observed protective antitumor effects generated by the vaccination. Similar results were observed using the HPV-16 E7 protein-based vaccination system. Thus, our data indicate that intramuscular administration of protein-based vaccines in conjunction with CpG followed by electroporation can significantly enhance the antigen-specific CD8+ T cell immune responses. The clinical implications of the study are discussed.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Electroporation*
  • Female
  • Injections, Intramuscular*
  • Mice
  • Mice, Inbred C57BL
  • Oligodeoxyribonucleotides / administration & dosage
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology*
  • Papillomavirus E7 Proteins / administration & dosage
  • Papillomavirus E7 Proteins / immunology*
  • Papillomavirus Infections / prevention & control
  • Vaccination / methods*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology

Substances

  • Adjuvants, Immunologic
  • CPG-oligonucleotide
  • Oligodeoxyribonucleotides
  • Papillomavirus E7 Proteins
  • Vaccines, Subunit
  • oncogene protein E7, Human papillomavirus type 16
  • Ovalbumin