title: Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6.
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.
authors.affiliation: Statens Serum Institut, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Ruhwald
authors.affiliation: Statens Serum Institut, Denmark.|Department of Pathology, Hvidovre Hospital, Denmark.
authors.forename: Lena
authors.initials: L
authors.lastname: de Thurah
authors.affiliation: Kilimanjaro Clinical Research Institute, Tanzania.
authors.forename: Davis
authors.initials: D
authors.lastname: Kuchaka
authors.affiliation: Molecular Immunology Unit, Al-Azhar University, Cairo, Egypt.|Animal Health Research Institute, Cairo, Egypt.
authors.forename: Mostafa Rafaat
authors.initials: MR
authors.lastname: Zaher
authors.affiliation: Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Salman
authors.affiliation: Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
authors.forename: Abdel-Rahman
authors.initials: AR
authors.lastname: Abdel-Ghaffar
authors.affiliation: Abbasia Chest hospital, Ministry of Health, Cairo, Egypt.
authors.forename: Faten Aly
authors.initials: FA
authors.lastname: Shoukry
authors.affiliation: Statens Serum Institut, Denmark.
authors.forename: Sascha Wilk
authors.initials: SW
authors.lastname: Michelsen
authors.affiliation: Statens Serum Institut, Denmark.
authors.forename: Bolette
authors.initials: B
authors.lastname: Soborg
authors.affiliation: Statens Serum Institut, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Blauenfeldt
authors.affiliation: Kibong'oto Infectious Diseases Hospital, Tanzania.
authors.forename: Stellah
authors.initials: S
authors.lastname: Mpagama
authors.affiliation: Statens Serum Institut, Denmark.
authors.forename: Søren T
authors.initials: ST
authors.lastname: Hoff
authors.affiliation: Statens Serum Institut, Denmark.
authors.forename: Else Marie
authors.initials: EM
authors.lastname: Agger
authors.affiliation: Statens Serum Institut, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Rosenkrands
authors.affiliation: Department of Pathology, Hvidovre Hospital, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Aagard
authors.affiliation: Kilimanjaro Clinical Research Institute, Tanzania.
authors.forename: Gibson
authors.initials: G
authors.lastname: Kibiki
authors.affiliation: Molecular Immunology Unit, Al-Azhar University, Cairo, Egypt.
authors.forename: Nabila
authors.initials: N
authors.lastname: El-Sheikh
authors.affiliation: Statens Serum Institut, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
mesh_terms: D000328:Adult; D000465:Algorithms; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D016022:Case-Control Studies; D015331:Cohort Studies; D003198:Computer Simulation; D005260:Female; D006801:Humans; D059425:Interferon-gamma Release Tests / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D012372:ROC Curve; D015203:Reproducibility of Results; D014376:Tuberculosis / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D010455:Peptides; D032581:Tuberculosis Vaccines