Enhancement of DNA vaccine potency through coadministration of CIITA DNA with DNA vaccines via gene gun

Daejin Kim, Talia Hoory, Archana Monie, Jenny Pan Yun Ting, Chien-Fu Hung, Tzyy Choou Wu

Research output: Contribution to journalArticle

Abstract

Administration of DNA vaccines via gene gun has emerged as an important form of Ag-specific immunotherapy. The MHC CIITA is a master regulator of MHC class II expression and also induces expression of class I molecules. We reasoned that the gene gun administration of CIITA DNA with DNA vaccines employing different strategies to improve MHC I and II processing could enhance DNA vaccine potency. We observed that DC-1 cells transfected with CIITA DNA lead to higher expression of MHC I and II molecules, leading to enhanced Ag presentation through the MHC I/II pathways. Furthermore, our data suggested that coadministration of DNA-encoding calreticulin (CRT) linked to human papillomavirus (HPV) 16 E6 Ag (CRT/E6) with CIITA DNA leads to enhanced E6-specific CD8 + T cell immune responses in vaccinated mice. In addition, coadministration of the combination of CRT/E6 DNA with CIITA DNA and DNA encoding the invariant chain (Ii) linked to the pan HLA-DR-reactive epitope (Ii-PADRE) further enhanced E6-specific CD8 + T cell immune responses in vaccinated mice. Treatment with the combination vaccine was also shown to enhance the antitumor effects and to prolong survival in TC-1 tumor-bearing mice. Vaccination with the combination vaccine also led to enhanced E6-specific CD8 + memory T cells and to long-term protection against TC-1 tumors and prolonged survival in vaccinated mice. Thus, our findings suggest that the combination of CIITA DNA with CRT/E6 and Ii-PADRE DNA vaccines represents a potentially effective means to combat tumors in the clinical setting.

Original languageEnglish (US)
Pages (from-to)7019-7027
Number of pages9
JournalJournal of Immunology
Volume180
Issue number10
StatePublished - 2008

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Vaccine Potency
DNA Vaccines
Firearms
Calreticulin
DNA
Genes
Combined Vaccines
T-Lymphocytes
Neoplasms
Human papillomavirus 16
HLA-DR Antigens
Immunotherapy
Epitopes
Vaccination

ASJC Scopus subject areas

  • Immunology

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Enhancement of DNA vaccine potency through coadministration of CIITA DNA with DNA vaccines via gene gun. / Kim, Daejin; Hoory, Talia; Monie, Archana; Ting, Jenny Pan Yun; Hung, Chien-Fu; Wu, Tzyy Choou.

In: Journal of Immunology, Vol. 180, No. 10, 2008, p. 7019-7027.

Research output: Contribution to journalArticle

Kim, Daejin ; Hoory, Talia ; Monie, Archana ; Ting, Jenny Pan Yun ; Hung, Chien-Fu ; Wu, Tzyy Choou. / Enhancement of DNA vaccine potency through coadministration of CIITA DNA with DNA vaccines via gene gun. In: Journal of Immunology. 2008 ; Vol. 180, No. 10. pp. 7019-7027.
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abstract = "Administration of DNA vaccines via gene gun has emerged as an important form of Ag-specific immunotherapy. The MHC CIITA is a master regulator of MHC class II expression and also induces expression of class I molecules. We reasoned that the gene gun administration of CIITA DNA with DNA vaccines employing different strategies to improve MHC I and II processing could enhance DNA vaccine potency. We observed that DC-1 cells transfected with CIITA DNA lead to higher expression of MHC I and II molecules, leading to enhanced Ag presentation through the MHC I/II pathways. Furthermore, our data suggested that coadministration of DNA-encoding calreticulin (CRT) linked to human papillomavirus (HPV) 16 E6 Ag (CRT/E6) with CIITA DNA leads to enhanced E6-specific CD8 + T cell immune responses in vaccinated mice. In addition, coadministration of the combination of CRT/E6 DNA with CIITA DNA and DNA encoding the invariant chain (Ii) linked to the pan HLA-DR-reactive epitope (Ii-PADRE) further enhanced E6-specific CD8 + T cell immune responses in vaccinated mice. Treatment with the combination vaccine was also shown to enhance the antitumor effects and to prolong survival in TC-1 tumor-bearing mice. Vaccination with the combination vaccine also led to enhanced E6-specific CD8 + memory T cells and to long-term protection against TC-1 tumors and prolonged survival in vaccinated mice. Thus, our findings suggest that the combination of CIITA DNA with CRT/E6 and Ii-PADRE DNA vaccines represents a potentially effective means to combat tumors in the clinical setting.",
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