Enhancing DNA vaccine potency by coadministration of DNA encoding antiapoptotic proteins
Tae Woo Kim, … , Sharad Kumar, T.-C. Wu
Tae Woo Kim, … , Sharad Kumar, T.-C. Wu
Published July 1, 2003
Citation Information: J Clin Invest. 2003;112(1):109-117. https://doi.org/10.1172/JCI17293.
View: Text | PDF
Article

Enhancing DNA vaccine potency by coadministration of DNA encoding antiapoptotic proteins

Abstract

Intradermal vaccination by gene gun efficiently delivers DNA vaccines into DCs of the skin, resulting in the activation and priming of antigen-specific T cells in vivo. DCs, however, have a limited life span, hindering their long-term ability to prime antigen-specific T cells. We reason that a strategy that prolongs the survival of DNA-transduced DCs will enhance priming of antigen-specific T cells and DNA vaccine potency. Here we show that codelivery of DNA encoding inhibitors of apoptosis (BCL-xL, BCL-2, XIAP, dominant negative caspase-9, or dominant negative caspase-8) with DNA encoding model antigens prolongs the survival of transduced DCs. More importantly, vaccinated mice exhibited significant enhancement in antigen-specific CD8+ T cell immune responses, resulting in a potent antitumor effect against antigen-expressing tumors. Among these antiapoptotic factors, BCL-xL demonstrated the greatest enhancement in antigen-specific immune responses and antitumor effects. Thus, coadministration of DNA vaccines with DNA encoding antiapoptotic proteins represents an innovative approach to enhance DNA vaccine potency.

Authors

Tae Woo Kim, Chien-Fu Hung, Morris Ling, Jeremy Juang, Liangmei He, J. Marie Hardwick, Sharad Kumar, T.-C. Wu

×

Figure 5

Options: View larger image (or click on image) Download as PowerPoint
Activation of E7-specific CD8+ T cells by CD11c-enriched cells isolated ...
Activation of E7-specific CD8+ T cells by CD11c-enriched cells isolated from the inguinal lymph nodes of vaccinated mice. Mice (three per group) were immunized and CD11c+ cells were enriched as described in the legend for Figure 4. CD11c-enriched cells were incubated with an E7-specific CD8+ T cell line. Cells were then stained for both CD8 and intracellular IFN-γ. Intracellular cytokine staining and flow-cytometry analysis were performed to determine the number of E7-specific IFN-γ–secreting CD8+ T cells per 5 × 104 cells. (a) Representative flow-cytometry data. The data shown here are from one representative experiment of three performed. (b) Bar graph depicting the number of E7-specific IFN-γ–secreting CD8+ T cells per 5 × 104 cells (mean ± SD).