Enhancement of protein vaccine potency by in vivo electroporation mediated intramuscular injection.
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.
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Tae Heung
TH
Kang
Archana
A
Monie
Lee S-F
LS
Wu
Xiaowu
X
Pang
Chien-Fu
CF
Hung
T-C
TC
Wu
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018274:Electroporation; D005260:Female; D007273:Injections, Intramuscular; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D050725:Papillomavirus E7 Proteins / Q000008:administration & dosage / Q000276:immunology*; D030361:Papillomavirus Infections / Q000517:prevention & control; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D050725:Papillomavirus E7 Proteins; D022223:Vaccines, Subunit; C059731:oncogene protein E7, Human papillomavirus type 16; D010047:Ovalbumin