Petrone Linda, Peruzzu Daniela, Altera Anna Maria Gerarda, Salmi Andrea, Vanini Valentina, Cuzzi Gilda, Coppola Andrea, Mellini Valeria, Gualano Gina, Palmieri Fabrizio, Panda Sudhasini, Peters Bjoern, Sette Alessandro, Arlehamn Cecilia Sofie Lindestam, Goletti Delia
Translational Research Unit, National Institute for Infectious Diseases "Lazzaro Spallanzani"-IRCCS, Rome, Italy.
Translational Research Unit, National Institute for Infectious Diseases "Lazzaro Spallanzani"-IRCCS, Rome, Italy; UOS Professioni Sanitarie Tecniche, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.
J Infect. 2024 Dec;89(6):106295. doi: 10.1016/j.jinf.2024.106295. Epub 2024 Sep 27.
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.
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.
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.
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.
鉴定阶段特异性抗原对于开发结核病（TB）诊断方法和疫苗至关重要。在一个结核病低流行国家，我们对结核分枝杆菌（Mtb）特异性免疫反应进行了表征，该反应针对一组Mtb衍生表位（ATB116），已证明其与结核病相关。
在这项前瞻性观察性横断面研究中，我们在基线和治疗结束时纳入了健康供体（HD）、结核病患者和结核感染（TBI）患者。用肽库刺激全血后的T细胞反应通过酶联免疫吸附测定（ELISA）、流式细胞术和多重分析进行表征。
无论感染/疾病情况如何，ATB116特异性干扰素-γ反应（通过ELISA）均与Mtb显著相关（p < 0.0001），且在结核病治疗期间下降（p = 0.0002）。流式细胞术证实，无论感染/疾病情况如何，ATB116特异性CD4 T细胞反应均与Mtb相关（p < 0.0001），并且与结核病相比，TBI中干扰素-γ/白细胞介素-2和中枢记忆T细胞的频率显著更高（分别为p = 0.016；p = 0.0242）。结核病治疗结束后，CD4 T细胞特异性反应下降。抗原特异性CD8 T细胞反应反映了CD4反应。最后，多重分析显示，ATB116在结核病和TBI中均诱导多种免疫因子。
我们对受结核病治疗调节的针对Mtb肽库的免疫反应进行了表征。这些结果对于我们理解结核病免疫发病机制和疫苗设计具有重要意义。
