These results indicate AEC/BC02 can protect against reactivation of latent infection and may function as a therapeutic vaccine.

Background Diagnostics to identify tuberculosis infection are limited. We aimed to assess the diagnostic accuracy and safety of the novel ESAT6-CFP10 (EC) skin test for tuberculosis infection in Chinese adults. Methods We conducted two randomized, parallel-group clinical trials in healthy participants and tuberculosis patients. All participants were tested with the T-SPOT.TB test, then received EC skin test and tuberculin skin test (TST). The diameter of skin indurations and/or redness at injection sites were measured at different time periods. A Bacillus Calmette Guerin (BCG) model was also established to assess the diagnosis of tuberculosis infection using EC skin test. Results In total, 777 healthy participants and 96 tuberculosis patients were allocated to receive the EC skin test at 1.0μg/0.1ml or 0.5μg/0.1ml. The area under the curve was 0.95 (95% CI, 0.91–0.97) from the EC skin test at a dose of 1.0μg/0.1ml at 24–72 hours. Compared to the T-SPOT.TB test, the EC skin test demonstrated similar sensitivity (87.5, 95% CI 77.8–97.2 versus 86.5, 95% CI 79.5–93.4) and specificity (98.9, 95% CI 96.0–99.9 versus 96.1, 95% CI 93.5–97.8). Among BCG vaccinated participants, the EC skin test had high consistency with the T-SPOT.TB test (96.3, 95% CI, 92.0–100.0). No serious adverse events related to the EC skin test were observed. Conclusions The EC skin test demonstrated both high specificity and sensitivity at a dose of 1.0μg/0.1ml, comparable to the T-SPOT.TB test. The diagnostic accuracy of the EC skin test was not impacted by BCG vaccination.

No abstract

Ag85b and HspX of Mycobacterium tuberculosis (Mtb) (H37Rv) were expressed and purified in this study. These two proteins were combined with another fusion protein CFP-10:ESAT-6 (C/E) (Ag), then mixed with the adjuvants CpG DNA and aluminum hydroxide and used to vaccinate mice and guinea pigs challenged with Mtb (H37Rv). The number of spleen lymphocytes secreting Ag85b, HspX and C/E-specific interferon-g were significantly higher in the Ag1Al1CpG group than in the Ag and CpG groups. The combination of Ag, Al and CpG induced the highest concentrations of anti-Ag85b, anti-HspX and anti-C/E immunoglobulin G in mouse serum. Mouse peritoneal macrophages from the Ag1Al1CpG group secreted significantly higher levels of interleukin-12 compared with macrophages from the other groups. The total mean liver, lung and spleen lesion scores and bacterial loads in the spleen in guinea pigs vaccinated with Ag1Al1CpG were lower than those of the other groups, but no significant difference was found. These results show that the mixture of Ag85b, HspX and C/E with a combination of CpG and aluminum adjuvants can induce both humoral and cellular immune responses in mice, whereas it plays only a small role in the control of disease progression in guinea pigs challenged with Mtb.

No abstract