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Therapeutic effect of DNA vaccines combined with chemotherapy in a latent infection model after aerosol infection of mice with Mycobacterium tuberculosis

Gene Therapy volume 10, pages 1592–1599 (2003)Cite this article

Abstract

The prevention of Mycobacterium tuberculosis (M. tuberculosis) reactivation would greatly reduce the incidence of the disease, particularly among the elderly. Here, we evaluated the efficacy of DNA vaccine in combination with a conventional TB chemotherapy on the prevention of M. tuberculosis reactivation. Mice were treated with isoniazid and pyrazinamide for 3 months from 4 weeks after aerosol infection with M. tuberculosis H37Rv. During this period of chemotherapy, DNA immunization was performed three times monthly with an antigen 85A (Ag85A) DNA or an IL-12 mutant (IL-12N220L) DNA, which is known to lead to a reduction in the secretion of the p40 subunit, but not of a bioactive IL-12p70. The reactivation of M. tuberculosis was dramatically reduced in mice treated with either Ag85A DNA (P<0.01) or IL-12N220L DNA (P<0.05) in combination with chemotherapy, compared with control mice receiving only chemotherapy. Ag85A DNA vaccine showed higher IFN-γ responses to Ag85A protein, but a lower response to culture filtrate than IL-12N220L DNA vaccine. In addition, Ag85A DNA vaccine prevented the reactivation of M. tuberculosis more efficiently than IL-12N220L DNA vaccine, indicating that Ag85A-specific IFN-γ response might correlate with M. tuberculosis control. This study suggests that immunotherapy using Ag85A or IL-12N220L DNA vaccine combined with conventional chemotherapy might be effective clinically for the prevention of tuberculosis reactivation and may offer a more effective cure for humans than chemotherapy alone.

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Acknowledgements

This work was supported by the grant of National Research Lab Program of the National S&T Program from Ministry of S&T (M1-0001-00-0089 and M10204000060-02J0000-05510), the grant of Vaccine Innovation Program from the Sequella Foundation, Rockville, MD, and the grants from Genexine Co., Ltd. and Daewoong Co., Ltd.

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  1. Y-C Sung and S-N Cho: The last two authors contributed equally to this work

Authors and Affiliations

  1. Department of Life Science, Pohang University of Science & Technology, Pohang, Korea

    S-J Ha, D-J Kim, M-K Song & Y-C Sung

  2. Department of Microbiology and Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea

    B-Y Jeon, S-C Kim & S-N Cho

  3. The International Vaccine Institute, Seoul, Korea

    S-N Cho

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  1. S-J Ha
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Ha, SJ., Jeon, BY., Kim, SC. et al. Therapeutic effect of DNA vaccines combined with chemotherapy in a latent infection model after aerosol infection of mice with Mycobacterium tuberculosis. Gene Ther 10, 1592–1599 (2003). https://doi.org/10.1038/sj.gt.3302057

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