Abstract:

Background: The tuberculin skin test, which uses purified protein derivative (PPD), is widely employed for tuberculosis screening. However, the tuberculin skin test cannot reliably distinguish between latent tuberculosis infection, BCG vaccination effects, and active tuberculosis disease. Therefore, more accurate diagnostic methods for tuberculosis are needed. The recombinant Mycobacterium tuberculosis fusion protein, composed of early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) derived from the reference strain H37Rv, demonstrates diagnostic potential for latent tuberculosis infection, active tuberculosis disease, and the immune status following BCG vaccination. Methods: The study was conducted in two phases. In the first phase, a randomized, blinded, self-controlled dual-arm skin test design with a comparator product was used to compare the sensitivity of different dose groups of recombinant Mycobacterium tuberculosis fusion protein and control reagents in pulmonary tuberculosis patients aged 18-65 years, as well as to their specificity in healthy subjects and non-tuberculous pulmonary diseases patients. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were calculated to determine the optimal diagnostic cut-off value for the recombinant Mycobacterium tuberculosis fusion protein. The concordance rates of the Mycobacterium tuberculosis fusion protein, the control reagent, and the interferon-gamma release assay (IGRA) were evaluated, along with safety assessment of the fusion protein. In the second phase, an open-label, single-arm design was adopted. Subjects aged 3-17 and 66-75 year-old received single-arm intradermal test to evaluate the safety of the recombinant Mycobacterium tuberculosis fusion protein. Discussion: This study aimed to assess the disagnostic efficacy of the recombinant Mycobacterium tuberculosis fusion protein for detecting latent tuberculosis infection and active tuberculosis, as well as to evaluate its safety profile. The clinical research findings are expected to facilitate the broader application of recombinant Mycobacterium tuberculosis fusion protein based diagnostic technology across diverse population and clinical settings.

Key words: Tuberculosis, Recombinant fusion proteins, Clinical trial