South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Division of Immunology, Department of Pathology, University of Cape Town.
AERAS, Rockville, Maryland.
Clin Infect Dis. 2019 Oct 30;69(10):1724-1730. doi: 10.1093/cid/ciz034.
Early 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).
Participants 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.
ESAT-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.
The 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.
早期分泌性抗原靶 6（ESAT-6）是一种免疫优势结核分枝杆菌（M.tb）抗原，包含在新型结核病（TB）疫苗和干扰素-γ（IFN-γ）释放试验（IGRAs）中。因此，在使用含有 ESAT-6 的疫苗接种后，获得一种不含 ESAT-6 的 IGRA 对于确定 M.tb 感染状态至关重要。我们旨在对最近开发的不含 ESAT-6 的 IGRA 进行定性，并将其与 QuantiFERON-TB Gold In-tube（QFT）进行比较，以评估其诊断性能。
招募了具有不同 M.tb 暴露水平和 TB 疾病的参与者，以确定不含 ESAT-6 的 IGRA 截止值，在独立队列中与标准 QFT 比较测试性能，并对含抗原的血液采集管进行技术定性。
在 QFT 阳性和 QFT 阴性南非青少年中评估了不含 ESAT-6 的 IGRA 抗原识别。根据未暴露于 M.tb 的对照和微生物学证实的肺结核患者的接收者操作特征分析，确定不含 ESAT-6 的 IGRA 截止值为 0.61IU/ml。在一个独立的健康青少年队列中，QFT 和不含 ESAT-6 的 IGRA 释放的 IFN-γ水平高度相关（P<0.0001，r=0.83），并且具有相似的阳性率，分别为 41.5%和 43.5%，两种测试之间的一致性为 91%（kappa=0.82；95%置信区间，0.74-0.90；McNemar 检验 P=0.48）。不含 ESAT-6 的 IGRA 血液采集管具有可接受的批间变异性、精密度和稳定性。
新型不含 ESAT-6 的 IGRA 具有与 QFT 相当的诊断准确性，适用于临床试验评估候选 TB 疫苗预防已建立的 M.tb 感染的疗效。
