A DNA vaccine co-expressing antigen and an anti-apoptotic molecule further enhances the antigen-specific CD8+ T-cell immune response

Tae Woo Kim, Chien Fu Hung, Meizi Zheng, David A K Boyd, Liangmei He, Sara I. Pai, T. C. Wu

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)493-499
Number of pages7
JournalJournal of Biomedical Science
Volume11
Issue number4
DOIs
Publication statusPublished - 2004 Jun 15
Externally publishedYes

Fingerprint

CD8 Antigens
DNA Vaccines
T-cells
Lysosome-Associated Membrane Glycoproteins
Vaccination
Caspase 3
T-Lymphocytes
Antigens
Apoptosis Regulatory Proteins
Molecules
Firearms
DNA
Genes
Human papillomavirus 16
Inbred C57BL Mouse
Sorting
Injections

Keywords

  • Anti-apoptosis
  • Bcl-xL
  • Caspase-3
  • DNA vaccines
  • Human papillomavirus
  • Immunotherapy
  • pVITRO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

A DNA vaccine co-expressing antigen and an anti-apoptotic molecule further enhances the antigen-specific CD8+ T-cell immune response. / Kim, Tae Woo; Hung, Chien Fu; Zheng, Meizi; Boyd, David A K; He, Liangmei; Pai, Sara I.; Wu, T. C.

In: Journal of Biomedical Science, Vol. 11, No. 4, 15.06.2004, p. 493-499.

Research output: Contribution to journalArticle

Kim, Tae Woo ; Hung, Chien Fu ; Zheng, Meizi ; Boyd, David A K ; He, Liangmei ; Pai, Sara I. ; Wu, T. C. / A DNA vaccine co-expressing antigen and an anti-apoptotic molecule further enhances the antigen-specific CD8+ T-cell immune response. In: Journal of Biomedical Science. 2004 ; Vol. 11, No. 4. pp. 493-499.
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AU - Boyd, David A K

AU - He, Liangmei

AU - Pai, Sara I.

AU - Wu, T. C.

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