Therapy modulates the response to T cell epitopes over the spectrum of tuberculosis infection

Abstract

Background: Identifying stage-specific antigens is essential for developing tuberculosis (TB) diagnostics and vaccines. In a low TB endemic country, we characterized, the Mycobacterium tuberculosis (Mtb)-specific immune response to a pool of Mtb-derived epitopes (ATB116), demonstrated as associated with TB disease.

Methods: In this prospective observational cross-sectional study, we enrolled healthy donors (HD), subjects with TB disease, and TB infection (TBI) at baseline and therapy completion. T-cell response after whole blood stimulation with the peptide pools was characterized by ELISA, flow cytometry, and multiplex assay.

Results: ATB116-specific IFN-γ response (by ELISA) significantly associates with Mtb regardless of infection/disease (p < 0.0001) and decreases during TB therapy (p = 0.0002). Flow cytometry confirms that ATB116-specific CD4⁺ T-cell response associated with Mtb regardless of infection/disease (p < 0.0001) and shows a significantly higher frequency of IFN-γ/IL-2 and central memory T-cells in TBI compared to TB (p = 0.016; p = 0.0242, respectively). CD4⁺ T cell-specific response decreases after TB therapy completion. The antigen-specific CD8⁺ T-cell response mirrors the CD4⁺ response. Finally, the multiplex assay analysis showed that ATB116 induces several immune factors in both TB and TBI.

Conclusion: We characterized the immune response to Mtb peptide pools that is modulated by TB therapy. These results are important for our understanding of TB immunopathogenesis and vaccine design.

Keywords: Antigen-specific response; CD4 response; IGRA; Peptides; T cells; TB therapy; Tuberculosis disease; Tuberculosis infection.