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...

PCRs targeting the 16S rRNA of MTC were more sensitive than those targeting 16S rDNA; 16S rRNA real-time RT-PCR showed the highest sensitivity and specificity for MTC.

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The aqueous fraction of Triton X‐100‐soluble proteins (TSP‐Aq) of Mycobacterium tuberculosis cell wall was reported to stimulate T‐cell responses in peripheral blood monocytes from tuberculosis (TB) patients and to induce Th1 cytokines, suggesting presence of protective antigens. In this study, therefore, we examined the protective efficacy of TSP‐Aq against M. tuberculosis infection in a mouse model. C57BL/6 mice were immunized with TSP‐Aq or culture filtrate proteins (CFP) mixed with incomplete Freund’s adjuvant or with BCG followed by i.v. challenge with M. tuberculosis H37Rv. TSP‐Aq induced strong interferon‐γ production by spleen cells, and mice immunized with TSP‐Aq antigens gave a significant reduction in M. tuberculosis CFU counts by 1.17–1.32 log10 CFU in the lungs and 1.31–2.08 log10 CFU in the spleen from 6 to 28 weeks. The degree of protection offered by TSP‐Aq was comparable to that of CFP and of the BCG vaccine. The results demonstrated that the TSP‐Aq antigens confer a significant level of protection against the growth of the organism in the lungs and spleen in a mouse model of TB and indicate that TSP contains major protective antigens of M. tuberculosis.