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Infection and Immunity, September 2005, p. 5666-5674, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5666-5674.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Optimization of Codon Usage Enhances the Immunogenicity of a DNA Vaccine Encoding Mycobacterial Antigen Ag85B

Hyun-Jeong Ko,¹ Sung-Youl Ko,¹ Yeon-Jeong Kim,¹ Eun-Gae Lee,² Sang-Nae Cho,² and Chang-Yuil Kang^1*

Laboratory of Immunology and Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea,¹ Department of Microbiology and Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea²

Received 5 January 2005/ Returned for modification 2 March 2005/ Accepted 12 April 2005

In spite of its many other benefits, DNA vaccine is limited in its application by its insufficient immunogenicity. One promising approach for enhancing its immunogenicity is to maximize its expression in the immunized host. In the current study, we investigated whether codon optimization of the mycobacterial antigen Ag85B gene could enhance the expression and immunogenicity of the Ag85B DNA vaccine. We generated a synthetic humanized Ag85B (hAg85B) gene in which codon usage was optimized for expression in human cells. DNA plasmids with codon-optimized hAg85B increased the level of protein expression in vitro and in vivo. DNA vaccine with hAg85B induced stronger Th1-like and cytotoxic T-cell immune responses in BALB/c mice and generated higher protective immunity in a BALB/c mouse model of Mycobacterium tuberculosis aerosol infection than did the DNA vaccine with wild-type Ag85B. Therefore, our results suggest that codon optimization of mycobacterial antigens (e.g., Ag85B) could improve protein expression and thereby enhance the immunogenicity of DNA vaccines against M. tuberculosis.

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* Corresponding author. Mailing address: Laboratory of Immunology and Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shillim-Dong, Kwanak-Gu, Seoul, 151-742, Republic of Korea. Phone: 82 2 880 7860. Fax: 82 2 885 1373. E-mail: cykang{at}snu.ac.kr.

Editor: J. L. Flynn

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Infection and Immunity, September 2005, p. 5666-5674, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5666-5674.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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