A DNA vaccine co-expressing antigen and an anti-apoptotic molecule further enhances the antigen-specific CD8+ T-cell immune response
- Authors
- Kim T.W.; Hung C.-F.; Zheng M.; Boyd D.A.K.; He L.; Pai S.I.; Wu T.-C.
- Issue Date
- 2004
- Keywords
- Anti-apoptosis; Bcl-xL; Caspase-3; DNA vaccines; Human papillomavirus; Immunotherapy; pVITRO
- Citation
- Journal of Biomedical Science, v.11, no.4, pp 493 - 499
- Pages
- 7
- Indexed
- SCOPUS
- Journal Title
- Journal of Biomedical Science
- Volume
- 11
- Number
- 4
- Start Page
- 493
- End Page
- 499
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/20856
- DOI
- 10.1159/000077899
- ISSN
- 1021-7770
1423-0127
- Abstract
- We have shown that DNA encoding the anti-apoptotic protein Bcl-xL enhances E7-specific CD8+ T-cell responses and DNA encoding pro-apoptotic protein caspase-3 suppresses E7-specific CD8+ T-cell responses when co-administered intradermally via gene gun with DNA encoding human papillomavirus type 16 (HPV-16) E7 linked to the sorting signal of the lysosome-associated membrane protein type 1 (LAMP-1). E7 and LAMP-1 are linked to form the chimeric Sig/E7/LAMP-1 (SEL). Because co-administration does not ensure delivery of both constructs to a single cell, we used pVITRO, a mammalian expression vector with double promoters, to ensure expression of both molecules in the same cell. We vaccinated C57BL/6 mice with pVITRO-SEL-Bcl-xL, pVITRO-SEL-mtBcl-xL, pVITRO-SEL, or pVITRO-SEL-caspase-3 intradermally via gene gun and intramuscularly via injection. We demonstrated that vaccination with pVITRO achieved similar results to a co-administration strategy: that Bcl-xL enhanced the E7-specific CTL response and caspase-3 suppressed the E7-specific CTL response. In addition, we found intradermal vaccination elicited significantly higher numbers of E7-specific CD8+ T cells compared to intramuscular vaccination. Thus, intradermal vaccination with a pVITRO vector combining an anti-apoptotic strategy (Bcl-xL) and an intracellular targeting strategy (SEL) further enhances the E7-specific CD8+ T-cell response and guarantees co-expression of both encoded molecules in transfected cells. Copyright © 2004 National Science Council, ROC and S. Karger AG, Basel.
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Collections - 3. Graduate School > Biomedical Research Center > 1. Journal Articles
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