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Type: Journal article
Title: Enhancing DNA vaccine potency by coadministration of DNA encoding antiapoptotic proteins
Author: Kim, T.
Hung, C.
Ling, M.
Juang, J.
He, L.
Hardwick, J.
Kumar, S.
Wu, T.
Citation: Journal of Clinical Investigation, 2003; 112(1):109-117
Publisher: Amer Soc Clinical Investigation Inc
Issue Date: 2003
ISSN: 0021-9738
Statement of
Tae Woo Kim, Chien-Fu Hung, Morris Ling, Jeremy Juang, Liangmei He, J. Marie Hardwick, Sharad Kumar, and T.-C. Wu
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.
Keywords: Dendritic Cells
CD8-Positive T-Lymphocytes
Mice, Inbred C57BL
Oncogene Proteins, Viral
Proto-Oncogene Proteins c-bcl-2
Vaccines, DNA
Antigens, CD
Papillomavirus E7 Proteins
bcl-X Protein
Lysosome-Associated Membrane Glycoproteins
Caspase 3
CD11c Antigen
DOI: 10.1172/JCI200317293
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