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Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6

View Article: PubMed Central - PubMed

ABSTRACT

There is a need for an improved vaccine for tuberculosis. ESAT-6 is a cardinal vaccine antigen with unique properties and is included in several vaccine candidates in development. ESAT-6 is also the core antigen in the IFN-γ release assays (IGRA) used to diagnose latent infection, rendering IGRA tests unspecific after vaccination. This challenge has prompted the development of a companion diagnostic for ESAT-6 based vaccines, an ESAT-6 free IGRA. We screened a panel of seven potential new diagnostic antigens not recognized in BCG vaccinated individuals. Three highly recognized antigens EspC, EspF and Rv2348c were identified and combined with CFP10 in an ESAT-6 free antigen cocktail. The cocktail was prepared in a field-friendly format, lyophilized with heparin in ready-to-use vacutainer tubes. The diagnostic performance of the ESAT-6 free IGRA was determined in a cross-validation study. Compared IGRA, the ESAT-6 free IGRA induced a comparable magnitude of IFN-γ release, and the diagnostic performance was on par with Quantiferon (sensitivity 84% vs 79%; specificity 99% vs 97%). The comparable performance of the ESAT-6 free IGRA to IGRA suggests potential as companion diagnostic for ESAT-6 containing vaccines and as adjunct test for latent infection.

No MeSH data available.


ROC Curve analysis comparing the diagnostic potential of ESAT-6 free IGRA and QFT (Qiagen).Analysis included samples from 74 patients and 100 controls. The Area Under the Curve reflects the antigen cocktails’ ability to differentiate between cases and controls. AUC for QFT (Qiagen) 0.96 (95% CI 0.92–0.99), ESAT-6 free IGRA (IFN-γ) 0.95 (95% CI 0.91–0.99). There was no significant difference between the ROC curves.
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f3: ROC Curve analysis comparing the diagnostic potential of ESAT-6 free IGRA and QFT (Qiagen).Analysis included samples from 74 patients and 100 controls. The Area Under the Curve reflects the antigen cocktails’ ability to differentiate between cases and controls. AUC for QFT (Qiagen) 0.96 (95% CI 0.92–0.99), ESAT-6 free IGRA (IFN-γ) 0.95 (95% CI 0.91–0.99). There was no significant difference between the ROC curves.

Mentions: The diagnostic potential of the ESAT-6 free IGRA was assessed in ROC curve analysis (Fig. 3). Here, the ESAT-6 free IGRA had a very high area under the curve (AUC) 0.95 (95% CI 0.91–0.99) not significantly different from QFT (Qiagen) 0.96 (95% CI 9.92–0.99).


Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6
ROC Curve analysis comparing the diagnostic potential of ESAT-6 free IGRA and QFT (Qiagen).Analysis included samples from 74 patients and 100 controls. The Area Under the Curve reflects the antigen cocktails’ ability to differentiate between cases and controls. AUC for QFT (Qiagen) 0.96 (95% CI 0.92–0.99), ESAT-6 free IGRA (IFN-γ) 0.95 (95% CI 0.91–0.99). There was no significant difference between the ROC curves.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384086&req=5

f3: ROC Curve analysis comparing the diagnostic potential of ESAT-6 free IGRA and QFT (Qiagen).Analysis included samples from 74 patients and 100 controls. The Area Under the Curve reflects the antigen cocktails’ ability to differentiate between cases and controls. AUC for QFT (Qiagen) 0.96 (95% CI 0.92–0.99), ESAT-6 free IGRA (IFN-γ) 0.95 (95% CI 0.91–0.99). There was no significant difference between the ROC curves.
Mentions: The diagnostic potential of the ESAT-6 free IGRA was assessed in ROC curve analysis (Fig. 3). Here, the ESAT-6 free IGRA had a very high area under the curve (AUC) 0.95 (95% CI 0.91–0.99) not significantly different from QFT (Qiagen) 0.96 (95% CI 9.92–0.99).

View Article: PubMed Central - PubMed

ABSTRACT

There is a need for an improved vaccine for tuberculosis. ESAT-6 is a cardinal vaccine antigen with unique properties and is included in several vaccine candidates in development. ESAT-6 is also the core antigen in the IFN-γ release assays (IGRA) used to diagnose latent infection, rendering IGRA tests unspecific after vaccination. This challenge has prompted the development of a companion diagnostic for ESAT-6 based vaccines, an ESAT-6 free IGRA. We screened a panel of seven potential new diagnostic antigens not recognized in BCG vaccinated individuals. Three highly recognized antigens EspC, EspF and Rv2348c were identified and combined with CFP10 in an ESAT-6 free antigen cocktail. The cocktail was prepared in a field-friendly format, lyophilized with heparin in ready-to-use vacutainer tubes. The diagnostic performance of the ESAT-6 free IGRA was determined in a cross-validation study. Compared IGRA, the ESAT-6 free IGRA induced a comparable magnitude of IFN-γ release, and the diagnostic performance was on par with Quantiferon (sensitivity 84% vs 79%; specificity 99% vs 97%). The comparable performance of the ESAT-6 free IGRA to IGRA suggests potential as companion diagnostic for ESAT-6 containing vaccines and as adjunct test for latent infection.

No MeSH data available.