Abstract
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), β2-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.
Original language | English (US) |
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Pages (from-to) | 7824-7831 |
Number of pages | 8 |
Journal | Vaccine |
Volume | 25 |
Issue number | 45 |
DOIs | |
State | Published - Nov 7 2007 |
Keywords
- BclxL
- Cancer immunotherapy
- DNA vaccines
- Dendritic cells
- E6
- Human papillomavirus-16 (HPV-16)
- Single chain trimer (SCT)
- Tumor treatment
ASJC Scopus subject areas
- Molecular Medicine
- General Immunology and Microbiology
- General Veterinary
- Public Health, Environmental and Occupational Health
- Infectious Diseases