Abstract
Intradermal administration of DNA vaccines, using a gene gun, represents an effective means of delivering DNA directly into professional antigen-presenting cells (APCs) in the skin and thus allows the application of strategies to modify the properties of APCs to enhance DNA vaccine potency. In the current study, we hypothesized that the potency of human papillomavirus (HPV) type 16 E7 DNA vaccines employing intracellular targeting strategies combined with a strategy to prolong the life of dendritic cells (DCs) could be further enhanced by the addition of a DNA vaccine capable of generating high numbers of pan-HLA-DR reactive epitope (PADRE)-specific CD4+ T cells. We observed that the addition of PADRE DNA to E7 DNA vaccines employing intracellular targeting strategies with a strategy to prolong the life of DCs led to significant enhancement of E7-specific CD8+ effector and memory T cells as well as significantly improved therapeutic effects against established E7-expressing tumors in tumor-challenged mice. Our data suggest that the potency of a DNA vaccine combining an intracellular targeting strategy as well as a strategy to prolong the life of DCs can be further enhanced by addition of DNA that is capable of generating high numbers of PADRE-specific CD4+ T cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1129-1139 |
| Number of pages | 11 |
| Journal | Human Gene Therapy |
| Volume | 18 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2007 |
Fingerprint
ASJC Scopus subject areas
- Genetics
Cite this
Enhancing DNA vaccine potency by combining a strategy to prolong dendritic cell life and intracellular targeting strategies with a strategy to boost CD4+ T cell. / Kim, Daejin; Hoory, Talia; Wu, Tzyy Choou; Hung, Chien-Fu.
In: Human Gene Therapy, Vol. 18, No. 11, 01.11.2007, p. 1129-1139.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enhancing DNA vaccine potency by combining a strategy to prolong dendritic cell life and intracellular targeting strategies with a strategy to boost CD4+ T cell
AU - Kim, Daejin
AU - Hoory, Talia
AU - Wu, Tzyy Choou
AU - Hung, Chien-Fu
PY - 2007/11/1
Y1 - 2007/11/1
N2 - Intradermal administration of DNA vaccines, using a gene gun, represents an effective means of delivering DNA directly into professional antigen-presenting cells (APCs) in the skin and thus allows the application of strategies to modify the properties of APCs to enhance DNA vaccine potency. In the current study, we hypothesized that the potency of human papillomavirus (HPV) type 16 E7 DNA vaccines employing intracellular targeting strategies combined with a strategy to prolong the life of dendritic cells (DCs) could be further enhanced by the addition of a DNA vaccine capable of generating high numbers of pan-HLA-DR reactive epitope (PADRE)-specific CD4+ T cells. We observed that the addition of PADRE DNA to E7 DNA vaccines employing intracellular targeting strategies with a strategy to prolong the life of DCs led to significant enhancement of E7-specific CD8+ effector and memory T cells as well as significantly improved therapeutic effects against established E7-expressing tumors in tumor-challenged mice. Our data suggest that the potency of a DNA vaccine combining an intracellular targeting strategy as well as a strategy to prolong the life of DCs can be further enhanced by addition of DNA that is capable of generating high numbers of PADRE-specific CD4+ T cells.
AB - Intradermal administration of DNA vaccines, using a gene gun, represents an effective means of delivering DNA directly into professional antigen-presenting cells (APCs) in the skin and thus allows the application of strategies to modify the properties of APCs to enhance DNA vaccine potency. In the current study, we hypothesized that the potency of human papillomavirus (HPV) type 16 E7 DNA vaccines employing intracellular targeting strategies combined with a strategy to prolong the life of dendritic cells (DCs) could be further enhanced by the addition of a DNA vaccine capable of generating high numbers of pan-HLA-DR reactive epitope (PADRE)-specific CD4+ T cells. We observed that the addition of PADRE DNA to E7 DNA vaccines employing intracellular targeting strategies with a strategy to prolong the life of DCs led to significant enhancement of E7-specific CD8+ effector and memory T cells as well as significantly improved therapeutic effects against established E7-expressing tumors in tumor-challenged mice. Our data suggest that the potency of a DNA vaccine combining an intracellular targeting strategy as well as a strategy to prolong the life of DCs can be further enhanced by addition of DNA that is capable of generating high numbers of PADRE-specific CD4+ T cells.
UR - http://www.scopus.com/inward/record.url?scp=36148987257&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36148987257&partnerID=8YFLogxK
U2 - 10.1089/hum.2007.090
DO - 10.1089/hum.2007.090
M3 - Article
C2 - 17939748
AN - SCOPUS:36148987257
VL - 18
SP - 1129
EP - 1139
JO - Human Gene Therapy
JF - Human Gene Therapy
SN - 1043-0342
IS - 11
ER -