Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Protective effect of DNA vaccine during chemotherapy on reactivation and reinfection of Mycobacterium tuberculosis

Gene Therapy volume 12, pages 634–638 (2005)Cite this article

Abstract

Active disease of tuberculosis (TB) can be developed decades later by either a relapse of the initial infection (endogenous reactivation) or by an entrance of the secondary infection (exogenous reinfection), since the current chemotherapy cannot lead to complete elimination of tuberculosis. Although the immunotherapeutic approaches in conjunction with conventional chemotherapy were tried to prevent TB growth via boosting the immune system, their therapeutic effects are still controversial. Here, we found that TB DNA vaccination completely blocked tuberculosis reactivation and significantly prevented from the secondary infection when chemotherapy was combined simultaneously. In particular, double-gene DNA vaccine composed of Ag85A and PstS-3 genes could reduce bacteria growth better than single-gene DNA vaccine after a secondary reinfection, indicating a correlation between the breadth of Th1 IFN-γ response and the efficacy of the protection from reinfection. Thus, we propose that multigene TB DNA immunotherapy including Ag85A and PstS-3 genes during the period of chemotherapy could benefit patients undergoing TB chemotherapy in prevention from exogenous reinfection as well as endogenous reactivation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Flynn JL, Chan J . Immunology of tuberculosis. Annu Rev Immunol 2001; 19: 93–129.

    Article  CAS  PubMed  Google Scholar 

  2. Kochi A, Nunn P, Dye C, Tayler E . Global burden of disease. Lancet 1997; 350: 142.

    Article  CAS  PubMed  Google Scholar 

  3. Kaufmann SH . Is the development of a new tuberculosis vaccine possible? Nat Med 2000; 6: 955–960.

    Article  CAS  PubMed  Google Scholar 

  4. Mitchison DA . The action of antituberculosis drugs in short-course chemotherapy. Tubercle 1985; 66: 219–225.

    Article  CAS  PubMed  Google Scholar 

  5. Bishai WR et al. Molecular and geographic patterns of tuberculosis transmission after 15 years of directly observed therapy. JAMA 1998; 280: 1679–1684.

    Article  CAS  PubMed  Google Scholar 

  6. Barnes PF, Cave MD . Molecular epidemiology of tuberculosis. N Engl J Med 2003; 349: 1149–1156.

    Article  CAS  PubMed  Google Scholar 

  7. van Rie A et al. Exogenous reinfection as a cause of recurrent tuberculosis after curative treatment. N Engl J Med 1999; 341: 1174–1179.

    Article  CAS  PubMed  Google Scholar 

  8. Bandera A et al. Molecular epidemiology study of exogenous reinfection in an area with a low incidence of tuberculosis. J Clin Microbiol 2001; 39: 2213–2218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Caminero JA et al. Exogenous reinfection with tuberculosis on a European island with a moderate incidence of disease.Am J Respir Crit Care Med 2001; 163: 717–720.

    Article  CAS  PubMed  Google Scholar 

  10. Denis O et al. Vaccination with plasmid DNA encoding mycobacterial antigen 85A stimulates a CD4+ and CD8+ T-cell epitopic repertoire broader than that stimulated by Mycobacterium tuberculosis H37Rv infection. Infect Immun 1998; 66: 1527–1533.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Huygen K et al. Immunogenicity and protective efficacy of a tuberculosis DNA vaccine. Nat Med 1996; 2: 893–898.

    Article  CAS  PubMed  Google Scholar 

  12. Tascon RE et al. Vaccination against tuberculosis by DNA injection. Nat Med 1996; 2: 888–892.

    Article  CAS  PubMed  Google Scholar 

  13. Tanghe A et al. Immunogenicity and protective efficacy of tuberculosis DNA vaccines encoding putative phosphate transport receptors. J Immunol 1999; 162: 1113–1119.

    CAS  PubMed  Google Scholar 

  14. Repique CJ, Li A, Collins FM, Morris SL . DNA immunization in a mouse model of latent tuberculosis: effect of DNA vaccination on reactivation of disease and on reinfection with a secondary challenge. Infect Immun 2002; 70: 3318–3323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Taylor JL et al. Pulmonary necrosis resulting from DNA vaccination against tuberculosis. Infect Immun 2003; 71: 2192–2198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Turner J et al. Effective preexposure tuberculosis vaccines fail to protect when they are given in an immunotherapeutic mode. Infect Immun 2000; 68: 1706–1709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lowrie DB et al. Therapy of tuberculosis in mice by DNA vaccination. Nature 1999; 400: 269–271.

    Article  CAS  PubMed  Google Scholar 

  18. Ha SJ et al. Therapeutic effect of DNA vaccines combined with chemotherapy in a latent infection model after aerosol infection of mice with Mycobacterium tuberculosis. Gene Therapy 2003; 10: 1592–1599.

    Article  CAS  PubMed  Google Scholar 

  19. Botha T, Ryffel B . Reactivation of latent tuberculosis by an inhibitor of inducible nitric oxide synthase in an aerosol murine model. Immunology 2002; 107: 350–357.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kamath AT et al. Differential protective efficacy of DNA vaccines expressing secreted proteins of Mycobacterium tuberculosis. Infect Immun 1999; 67: 1702–1707.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Doria-Rose NA, Haigwood NL . DNA vaccine strategies: candidates for immune modulation and immunization regimens. Methods 2003; 31: 207–216.

    Article  CAS  PubMed  Google Scholar 

  22. Mendez S, Belkaid Y, Seder RA, Sacks D . Optimization of DNA vaccination against cutaneous leishmaniasis. Vaccine 2002; 20: 3702–3708.

    Article  CAS  PubMed  Google Scholar 

  23. Morris S et al. The immunogenicity of single and combination DNA vaccines against tuberculosis. Vaccine 2000; 18: 2155–2163.

    Article  CAS  PubMed  Google Scholar 

  24. Kong WP et al. Immunogenicity of multiple gene and clade human immunodeficiency virus type 1 DNA vaccines. J Virol 2003; 77: 12764–12772.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wiker HG, Harboe M . The antigen 85 complex: a major secretion product of Mycobacterium tuberculosis. Microbiol Rev 1992; 56: 648–661.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. D'Souza S et al. CD4+ T cells contain Mycobacterium tuberculosis infection in the absence of CD8+ T cells in mice vaccinated with DNA encoding Ag85A. Eur J Immunol 2000; 30: 2455–2459.

    Article  CAS  PubMed  Google Scholar 

  27. D'Souza S et al. Improved tuberculosis DNA vaccines by formulation in cationic lipids. Infect Immun 2002; 70: 3681–3688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Romano M et al. Induction of in vivo functional Db-restricted cytolytic T cell activity against a putative phosphate transport receptor of Mycobacterium tuberculosis. J Immunol 2004; 172: 6913–6921.

    Article  CAS  PubMed  Google Scholar 

  29. van Pinxteren LA et al. Control of latent Mycobacterium tuberculosis infection is dependent on CD8 T cells. Eur J Immunol 2000; 30: 3689–3698.

    Article  CAS  PubMed  Google Scholar 

  30. Park SH et al. Efficient induction of T helper 1 CD4+ T-cell responses to hepatitis C virus core and E2 by a DNA prime-adenovirus boost. Vaccine 2003; 21: 4555–4564.

    Article  CAS  PubMed  Google Scholar 

  31. Ha SJ et al. IL-23 induces stronger sustained CTL and Th1 immune responses than IL-12 in hepatitis C virus envelope protein 2 DNA immunization. J Immunol 2004; 172: 525–531.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the grants of National Research Lab Program of the National S&T Program from the Ministry of S&T (M1-0204-00-0146 and M10204000060-02J0000-05510) and the grants from Genexine Co., Ltd. and Daewoong Co., Ltd. We thank Jin-Won Youn for devoted helpful discussion.

Author information

Author notes

  1. S-J Ha, B-Y Jeon, S-N Cho and Y-C Sung: These authors contributed equally to this work

Authors and Affiliations

  1. Division of Molecular and Life Sciences, Postech Biotech Center, Pohang University of Science & Technology, Pohang, Republic of Korea

    S-J Ha, J-I Youn & Y-C Sung

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

    B-Y Jeon, S-C Kim & S-N Cho

  3. The International Vaccine Institute, Seoul, Republic of Korea

    S-N Cho

Authors
  1. S-J Ha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B-Y Jeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J-I Youn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S-C Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S-N Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y-C Sung
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ha, SJ., Jeon, BY., Youn, JI. et al. Protective effect of DNA vaccine during chemotherapy on reactivation and reinfection of Mycobacterium tuberculosis. Gene Ther 12, 634–638 (2005). https://doi.org/10.1038/sj.gt.3302465

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gt.3302465

Keywords

This article is cited by

Search

Advanced search

Quick links