ESAT-6 and CFP-10 antigens as a biotechnology molecule substrate. Applications in medicine

Abstract

Recombinant technologies have been long widely used in medicine. This article presents a review on the application of medical technologies based on ESAT-6 and CFP-10 proteins in diagnostics and prevention of tuberculosis. ESAT-6 and CFP-10 are specific proteins whose genes are encoded in the RD-1 zone (region of difference) of M. tuberculosis. M. bovis BCG and in most nontuberculous mycobacteria lack the RD-1 genome fragment. The discovery of ESAT-6 and CFP-10 antigens allowed to make the first and so far, the only breakthrough in improving the diagnostics of latent tuberculosis infection after the first tuberculin skin test (TST) was implemented. The article describes the principle of action and the experience with diagnostic tools based on ESAT-6 and CFP-10 such as in vitro interferon-gamma release assays (IGRA) and in vivo recombinant tuberculosis allergen (RTA, Diaskintest). RTA is inoculated intradermally similar to TST followed by developing delayed-type immune reaction detected in the area closest to M. tuberculosis. Combined use of ESAT-6 and CFP-10 for early detection of tuberculosis infection allowed to ameliorate for many drawbacks related to TST. High sensitivity and specificity was confirmed for ESAT-6- and CFP-10-based tests, so that former BCG vaccination had no more effect on test results and lowered frequency of false positive results due to reaction to non-tuberculous mycobacteria. The results of a large-scale meta-analysis on studies with patients at high risk demonstrated that the risk of developing tuberculosis in subjects with positive vs. negative IGRA was increased by 9.35-fold (95% confidence interval (CI [6.4813.49]), whereas for TST by 4.24-fold (95% CI [3.35.46]). 95.1%, (95% CI [95.0695.1]). Analyzing available publications demonstrated sufficient evidence base regarding efficacy of using ESAT-6CFP-10-based tests in tuberculosis diagnostics. Finally, there are also reviewed the diagnostic tests and vaccines based on using such proteins currently being under development.