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Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects

Abstract

Genetic immunization strategies have largely focused on the use of plasmid DNA with a gene gun. However, there remains a clear need to further improve the efficiency, safety, and cost of potential DNA vaccines. The gold particle-coated DNA format delivered through a gene gun is expensive, time and process consuming, and raises aseptic safety concerns. This study aims to determine whether a low-pressured gene gun can deliver noncarrier naked DNA vaccine without any particle coating, and generate similarly strong antigen-specific immunologic responses and potent antitumor effects compared with gold particle-coated DNA vaccine. Our results show that mice vaccinated with noncarrier naked chimeric CRT/E7 DNA lead to dramatic increases in the numbers of E7-specific CD8+ T-cell precursors and markedly raised titers of E7-specific antibodies. Furthermore, noncarrier naked CRT/E7 DNA vaccine generated potent antitumor effects against subcutaneous E7-expressing tumors and pre-established E7-expressing metastatic pulmonary tumors. In addition, mice immunized with noncarrier naked CRT/E7 DNA vaccine had significantly less burning effects on the skin compared with those vaccinated with gold particle-coated CRT/E7 DNA vaccine. We conclude that noncarrier naked CRT/E7 DNA vaccine delivered with a low-pressured gene gun can generate similarly potent immunologic responses and effective antitumor effects has fewer side effects, and is more convenient than conventional gold particle-coated DNA vaccine.

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Acknowledgements

This study was supported by a grant from the New Century Health Care Promotion Foundation and in part by the Department of Medical Research of NTUH. The E7-specific CD8+ T-cell line and TC-1 tumor cell line were kindly provided by Dr TC Wu of Johns Hopkins Medical Institutes in Baltimore, MD, USA. The pCMV-Luciferase DNA was kindly provided by Dr MD Lai of National Cheng Kung University in Tainan, Taiwan.

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Correspondence to W-F Cheng.

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Chen, CA., Chang, MC., Sun, WZ. et al. Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects. Gene Ther 16, 776–787 (2009). https://doi.org/10.1038/gt.2009.31

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