• Elisa Nemes, Deborah Abrahams, Thomas J Scriba, Frances Ratangee, Alana Keyser, Lebohang Makhethe, Mzwandile Erasmus, Simbarashe Mabwe, Nicole Bilek, Virginie Rozot, Hennie Geldenhuys, Mark Hatherill, Maria D Lempicki, Line Lindebo Holm, Leah Bogardus, Ann M Ginsberg, Thomas Blauenfeldt, Bronwyn Smith, Ruth D Ellis, Andre G Loxton, Gerhard Walzl, Peter Andersen, and Morten Ruhwald.
• South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Division of Immunology, Department of Pathology, University of Cape Town.
• Clin. Infect. Dis. 2019 Oct 30; 69 (10): 1724-1730.

BackgroundEarly secretory antigenic target-6 (ESAT-6) is an immunodominant Mycobacterium tuberculosis (M.tb) antigen included in novel vaccines against tuberculosis (TB) and in interferon-gamma (IFN-γ) release assays (IGRAs). Therefore, the availability of an ESAT-6-free IGRA is essential to determine M.tb infection status following vaccination with ESAT-6-containing vaccines. We aimed to qualify a recently developed ESAT-6-free IGRA and to assess its diagnostic performance in comparison to QuantiFERON-TB Gold In-tube (QFT).MethodsParticipants with different levels of M.tb exposure and TB disease were enrolled to determine the ESAT-6-free IGRA cutoff, test assay performance in independent cohorts compared to standard QFT, and perform a technical qualification of antigen-coated blood collection tubes.ResultsESAT-6-free IGRA antigen recognition was evaluated in QFT-positive and QFT-negative South African adolescents. The ESAT-6-free IGRA cutoff was established at 0.61 IU/mL, based on receiver operating characteristic analysis in M.tb-unexposed controls and microbiologically confirmed pulmonary TB patients. In an independent cohort of healthy adolescents, levels of IFN-γ released in QFT and ESAT-6-free IGRA were highly correlated (P < .0001, r = 0.83) and yielded comparable positivity rates, 41.5% and 43.5%, respectively, with 91% concordance between the tests (kappa = 0.82; 95% confidence interval, 0.74-0.90; McNemar test P = .48). ESAT-6-free IGRA blood collection tubes had acceptable lot-to-lot variability, precision, and stability.ConclusionsThe novel ESAT-6-free IGRA had diagnostic accuracy comparable to QFT and is suitable for use in clinical trials to assess efficacy of candidate TB vaccines to prevent established M.tb infection.© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

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