Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6.
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 tes...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Nature Publishing Group
2017
|
| _version_ | 1797055965702389760 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Ruhwald, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:16:50Z |
| format | Journal article |
| id | oxford-uuid:18aff2a1-2a7a-4832-9b8f-2c63ba51ecf2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:16:50Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:18aff2a1-2a7a-4832-9b8f-2c63ba51ecf22022-03-26T10:44:37ZIntroducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:18aff2a1-2a7a-4832-9b8f-2c63ba51ecf2EnglishSymplectic Elements at OxfordNature Publishing Group2017Ruhwald, Mde Thurah, LKuchaka, DZaher, MRSalman, AMAbdel-Ghaffar, A-RShoukry, FAMichelsen, SWSoborg, BBlauenfeldt, TMpagama, SHoff, STAgger, EMRosenkrands, IAagard, CKibiki, GEl-Sheikh, NAndersen, PThere 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. |
| spellingShingle | 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 Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6. |
| title | Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6. |
| title_full | Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6. |
| title_fullStr | Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6. |
| title_full_unstemmed | Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6. |
| title_short | Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6. |
| title_sort | introducing the esat 6 free igra a companion diagnostic for tb vaccines based on esat 6 |
| work_keys_str_mv | AT ruhwaldm introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT dethurahl introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT kuchakad introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT zahermr introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT salmanam introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT abdelghaffarar introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT shoukryfa introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT michelsensw introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT soborgb introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT blauenfeldtt introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT mpagamas introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT hoffst introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT aggerem introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT rosenkrandsi introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT aagardc introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT kibikig introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT elsheikhn introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 AT andersenp introducingtheesat6freeigraacompaniondiagnosticfortbvaccinesbasedonesat6 |