Mycobacterium tuberculosis Region of Difference (RD) 2 Antigen Rv1985c and RD11 Antigen Rv3425 Have the Promising Potential To Distinguish Patients with Active Tuberculosis from M. bovis BCG-Vaccinated Individuals

Abstract

e Antigens encoded in the region of difference (RD) of Mycobacterium tuberculosis constitute a potential source of specific immunodiagnostic antigens for distinguishing tuberculosis (TB) infection from BCG vaccination. We evaluated the diagnostic potential of specific T-cell epitopes selected from two immunodominant antigens, Rv1985c and Rv3425, from RD2 and RD11, respectively, on the basis of epitope mapping, in TB patients and BCG-vaccinated healthy individuals. Using a whole-blood gamma interferon release assay, a wide array of epitopes was recognized on both Rv1985c and Rv3425 in TB patients. Those epitopes that could specifically discriminate TB infection from BCG vaccination were carefully selected, and the most promising peptide pools from Rv1985c showed a sensitivity of 53.9% and a specificity of 95.5%. When the novel specific peptides from Rv1985c joined the diagnostic antigens in the QuantiFERON-TB Gold In-Tube (QFT-IT) assay, the sensitivity was increased from 86.4% to 96.2%, with no drop in specificity. These results indicate that the peptide pools selected from Rv1985c and Rv3425 have the potential to diagnose TB infection by a method that may be routinely used in clinical laboratories.

Immunological evaluation of a novel Mycobacterium tuberculosis antigen, Rv3117, absent in Mycobacterium bovis BCG

“…4). These results were consistent with those of the RD11-encoded antigen Rv3245 (19), which is now in further and preclinical studies in China (9,(36)(37)(38). These data indicated that IFA may be used as one of the most optimal adjuvants for Rv3117-based vaccine studies in animal models.…”

QuantiFERON-TB performance enhanced by novel Mycobacterium tuberculosis-specific antigens

“…The addition of the novel peptides to the QFT resulted in a significant increase in the IFN-γ release in active TB, without altering specificity, and also in the BCG-vaccinated control population. This is consistent with previous data in the literature indicating that the addition of other non-RD1 proteins to QFT can result in an increase of the test performance [4,5], as also observed in the changes implemented in the QFT test versions [1].…”

“…To improve the performance of the IGRAs, addition of MTB antigens TB7.7, Rv3425 and EsxV to the current antigen cocktail has already been attempted [4,5]. Following a similar strategy, we evaluated the addition of six novel peptides to the QFT antigen cocktail to improve the diagnostic performance in terms of accuracy and dynamic range of interferon (IFN)-γ level in active TB patients.…”

“…The document highlights MDR-TB as a core area, emphasising the moral duty of preventing the selection of MDR-TB (by treating susceptible cases correctly with first-line drugs) and the necessary efforts to treat it when diagnosed. Unfortunately, treating MDR-and extensively drug-resistant (XDR)-TB is much more onerous, lengthy and terribly expensive; treatment outcomes remain suboptimal, adverse events being frequent and severe [3][4][5][6]. The availability of new drugs has offered new possibilities for saving patients who were not previously treatable and posed new challenges related to their rational use in order to prevent selection of resistant strains of Mycobacterium tuberculosis [7][8][9][10].…”

Secreted Rv1768 From RD14 of Mycobacterium tuberculosis Activates Macrophages and Induces a Strong IFN-γ-Releasing of CD4+ T Cells

“…PE/PPE proteins located in RD regions are considered to be the most promising candidates for TB vaccine development and diagnostic agents, especially secreted antigens (Abraham et al, 2018). Rv3425 (PPE57), which locates in the RD11 region and induces macrophage activation by augmenting the expression of MHC-II and pro-inflammatory cytokines (TNF-α, IL-6, and IL-12p40), has been confirmed with the potential to distinguish patients with active TB via QFT assay (Wang et al, 2013; Losi et al, 2016) and for use as an antigen for therapeutic or protective vaccine design (Xu et al, 2014; Yang et al, 2015). In this study, Rv1768 evoked a significantly high level of IFN-γ in H37Rv-infected mice, but not BCG-infected or normal mice.…”