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

Morten Ruhwald; Lena de Thurah; Davis Kuchaka; Mostafa Rafaat Zaher; Ahmed M Salman; Abdel-Rahman Abdel-Ghaffar; Faten Aly Shoukry; Sascha Wilk Michelsen; Bolette Soborg; Thomas Blauenfeldt; Stellah Mpagama; Søren T Hoff; Else Marie Agger; Ida Rosenkrands; Claus  Aagard; Gibson Kibiki; Nabila El-Sheikh; Peter Andersen

doi:10.1038/srep45969

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

Morten Ruhwald
, Lena de Thurah
, Davis Kuchaka
, Mostafa Rafaat Zaher
, Ahmed M Salman
, Abdel-Rahman Abdel-Ghaffar
, Faten Aly Shoukry
, Sascha Wilk Michelsen
, Bolette Soborg
, Thomas Blauenfeldt
, Stellah Mpagama
, Søren T Hoff
, Else Marie Agger
, Ida Rosenkrands
, Claus Aagard
, Gibson Kibiki
, Nabila El-Sheikh
, Peter Andersen

Department of Pathology

27 Citations (Scopus)

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.

Original language	English
Journal	Scientific Reports
Volume	7
Issue number	45969
ISSN	2045-2322
DOIs	https://doi.org/10.1038/srep45969
Publication status	Published - 1 Apr 2017

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10.1038/srep45969

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Ruhwald, M., de Thurah, L., Kuchaka, D., Zaher, M. R., Salman, A. M., Abdel-Ghaffar, A.-R., Shoukry, F. A., Michelsen, S. W., Soborg, B., Blauenfeldt, T., Mpagama, S., Hoff, S. T., Agger, E. M., Rosenkrands, I., Aagard, C., Kibiki, G., El-Sheikh, N., & Andersen, P. (2017). Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6. Scientific Reports, 7(45969). https://doi.org/10.1038/srep45969

Ruhwald, M, de Thurah, L, Kuchaka, D, Zaher, MR, Salman, AM, Abdel-Ghaffar, A-R, Shoukry, FA, Michelsen, SW, Soborg, B, Blauenfeldt, T, Mpagama, S, Hoff, ST, Agger, EM, Rosenkrands, I, Aagard, C, Kibiki, G, El-Sheikh, N & Andersen, P 2017, 'Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6', Scientific Reports, vol. 7, no. 45969. https://doi.org/10.1038/srep45969

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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.",

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AU - Agger, Else Marie

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N2 - 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.

AB - 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.

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

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