Immunogenicity and protective efficacy of a tuberculosis DNA vaccine

Huygen, Kris; Denis, Olivier; Dl, Montgomery; Am, Yawman; Rr, Deck; Cm, DeWitt; Im, Orme; Baldwin, Susan L.; D’Souza, Celine; Drowart, Annie; Lozes, E; Vandenbussche, Pierre-Yves; Vooren, Van; Ma, Liang; Jb, Ulmer

doi:10.1038/nm0896-893

Cited by 589 publications

(410 citation statements)

References 27 publications

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“…Moreover, mouse immunization experiments have shown that vaccination with DNA encoding Ag85A could generate strong CD4 + T-cell-mediated Th1 and CD8 + T-cell-mediated CTL responses and be responsible for improved protection against challenge by virulent M. tuberculosis in animal models. [15][16][17] In the present study, we demonstrate for the first time that Ag85A DNA vaccine could also be effective at reducing the reactivation of established M. tuberculosis (Table 1 and Figure 4). Rates of reactivation in both lungs and spleens were found to be inversely correlated with the Ag85A-specific IFN-g production level, but not with the CFspecific IFN-g level (Figures 3a and b), indicating that Ag85A-specific Th1 immunity may be more important than Th1 immune response specific for CF in terms of protection against M. tuberculosis reactivation.…”

Section: Discussionmentioning

confidence: 54%

“…Prophylactic DNA vaccines expressing M. tuberculosis antigens or cytokines are of particular interest, because of their efficiency and long-lasting effect in animal TB models. For example, prophylactic DNA vaccines expressing various M. tuberculosis antigens, including Ag85A, [15][16][17] Ag85B, 17,18 65 kDa heat shock protein, 19,20 and PstS-3 21 , were found to be effective at limiting the growth of M. tuberculosis in mice. In contrast, there has been little evidence that DNA vaccines are useful as therapeutic vaccines against TB.…”

Section: Introductionmentioning

confidence: 99%

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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

Jeon

Kim

et al. 2003

Gene Ther

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Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

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

Jeon

Kim

et al. 2003

Gene Ther

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“…In prophylactic settings, there are several reports that DNA vaccines expressing M. tuberculosis antigens are effective for limiting the bacterial growth in mice. [10][11][12][13] However, it is still controversial whether DNA vaccines work against TB reactivation in postexposure models. [14][15][16] For example, the vaccination of plasmid DNA expressing hsp65 after completion of chemotherapy was shown to be effective in preventing the reactivation of intravenously infected M. tuberculosis.…”

mentioning

confidence: 99%

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

Jeon

Youn

et al. 2005

Gene Ther

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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-g 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. Gene Therapy (2005) Tuberculosis (TB) holds the dubious honor of being the leading single-agent infectious disease killer in the world 1,2 and the situation is worsened by the increasing incidence of both multidrug resistant (MDR) stains and combination with AIDS. 1,3 After Mycobacterium tuberculosis infection, active disease arises in about 5% of exposed individuals and most of the others will develop a latent infection in which the tubercle bacilli can persist in vivo without causing any clinical symptoms. However, active disease may also develop decades later either as a relapse of the initial infection or because of a secondary infection. Although most cases of tuberculosis were once believed to result from a endogenous reactivation acquired in the past, 4 recent studies indicate that onethird of tuberculosis cases are due to recent transmission by exogenous reinfection of multiple M. tuberculosis strains, [5][6][7][8][9] implicating that the exogenous reinfection significantly contributes to disease transmission. Therefore, novel immunotherapeutic approaches will be required to prevent reinfection as well as reactivation of M. tuberculosis in individuals with latent tuberculosis.DNA vaccination has become a promising strategy for developing an effective vaccine against TB, since it efficiently induces Th1 immunity, an essential arm of immune system to clear the bacteria. In prophylactic settings, there are several reports that DNA vaccines expressing M. tuberculosis antigens are effective for limiting the bacterial growth in mice. 10-13 However, it is still controversial whether DNA vaccines work against TB reactivation in postexposure models. 14-16 For example, the vaccination of plasmid DNA expressing hsp65 after completion of chemotherapy was shown to be effective in preventing the reactivation of intravenou...

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“…Hence, a Th1 response is probably required for 10,18,19 In contrast, a Th2 response is abundant during infection with M. tuberculosis, and thus a shift in the balance toward a Th1 response may be beneficial. 20,21 DNA vaccination can achieve such a shift particularly because of its own 'adjuvant' effect.…”

Section: Discussionmentioning

confidence: 99%

Efficient tuberculosis treatment in mice using chemotherapy and immunotherapy with the combined DNA vaccine encoding Ag85B, MPT-64 and MPT-83

Cai

2008

Gene Ther

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Although most cases of tuberculosis (TB) can be cured with antibiotics, relapse is common if patients do not continue chemotherapy for at least 6 months. Thus, improved therapeutic strategies are urgently needed. We previously found that the combined DNA vaccine encoding the Mycobacterium tuberculosis proteins Ag85B, MPT-64 and MPT-83 protected mice from TB following H37Rv challenge and considered whether this combined DNA vaccine has a therapeutic effect. In the present work, we demonstrate that boosting the efficiency of the immune system with the combined DNA vaccine may be a valuable adjunct to shorten the duration of antibacterial chemotherapy. Mice treated with the combined DNA vaccine along with isoniazid and pyrazinamide showed significantly higher interferon-g responses to a mixture of the three specific antigens (Po0.001), which were accompanied by a significant reduction in colony-forming unit in H37Rv-infected animals 3-5 months after treatment (Po0.001). These results suggest that the combined DNA vaccine along with conventional TB chemotherapy has strong potential for TB immunotherapy and may provide new alternatives to control the disease.

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Immunogenicity and protective efficacy of a tuberculosis DNA vaccine

Cited by 589 publications

References 27 publications

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

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

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

Efficient tuberculosis treatment in mice using chemotherapy and immunotherapy with the combined DNA vaccine encoding Ag85B, MPT-64 and MPT-83

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