Prediction of Th1 and Cytotoxic T Lymphocyte Epitopes of
            <i>Mycobacterium tuberculosis</i>
            and Evaluation of Their Potential in the Diagnosis of Tuberculosis in a Mouse Model and in Humans

Gong, Wenping; Liang, Yan; Wang, Jie; Liu, Yinping; Xue, Yong; Mi, Jie; Li, Pengchuan; Wang, Xiaoou; Wang, Lan; Wu, Xueqiong

doi:10.1128/spectrum.01438-22

Cited by 7 publications

(9 citation statements)

References 48 publications

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“…The PBMCs and cell culture medium mixture was transferred to a new tube and centrifuged at 500 g for 10 min. Finally, the supernatant was gently transferred to another new tube, and levels of interleukin-2 (IL-2), IL-4, IL-6, IL-10, IFN-γ, tumor necrosis factor-α (TNF-α), and IL-17A were measured with a human Th1/Th2/Th17 cytokine kit (Cat 560485) following our previous studies ( 28 , 49 , 50 ).…”

Section: Methodsmentioning

confidence: 99%

Bioinformatics analysis and consistency verification of a novel tuberculosis vaccine candidate HP13138PB

et al. 2023

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BackgroundWith the increasing incidence of tuberculosis (TB) and the shortcomings of existing TB vaccines to prevent TB in adults, new TB vaccines need to be developed to address the complex TB epidemic.MethodThe dominant epitopes were screened from antigens to construct a novel epitope vaccine termed HP13138PB. The immune properties, structure, and function of HP13138PB were predicted and analyzed with bioinformatics and immunoinformatics. Then, the immune responses induced by the HP13138PB were confirmed by enzyme-linked immunospot assay (ELISPOT) and Th1/Th2/Th17 multi-cytokine detection kit.ResultThe HP13138PB vaccine consisted of 13 helper T lymphocytes (HTL) epitopes, 13 cytotoxic T lymphocytes (CTL) epitopes, and 8 B-cell epitopes. It was found that the antigenicity, immunogenicity, and solubility index of the HP13138PB vaccine were 0.87, 2.79, and 0.55, respectively. The secondary structure prediction indicated that the HP13138PB vaccine had 31% of α-helix, 11% of β-strand, and 56% of coil. The tertiary structure analysis suggested that the Z-score and the Favored region of the HP13138PB vaccine were -4.47 88.22%, respectively. Furthermore, the binding energies of the HP13138PB to toll-like receptor 2 (TLR2) was -1224.7 kcal/mol. The immunoinformatics and real-world experiments showed that the HP13138PB vaccine could induce an innate and adaptive immune response characterized by significantly higher levels of cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and IL-10.ConclusionThe HP13138PB is a potential vaccine candidate to prevent TB, and this study preliminarily evaluated the ability of the HP13138PB to generate an immune response, providing a precursor target for developing TB vaccines.

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Section: Methodsmentioning

confidence: 99%

Bioinformatics analysis and consistency verification of a novel tuberculosis vaccine candidate HP13138PB

et al. 2023

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“…Study four (22) also adopted a case–control study design and probably overestimated the accuracy of the differential diagnosis as mentioned by the researchers as well. In addition, 70 Th1 cytokines have been identified in relation to tuberculosis (42). These 70 cytokines could have been investigated further by the researchers and selected in a more focused manner to which cytokines out of the 70 are more specific for LTBI (42).…”

Section: Resultsmentioning

confidence: 99%

Latent Tuberculosis Diagnostics: A Systematic Review What is the past, present, and future in the diagnosis of latent tuberculosis?

Kostoudi,

Hammond

2024

Preprint

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Background: Tuberculosis (TB) is the second leading infectious killer after COVID-19 and the 13th leading cause of death worldwide. Latent tuberculosis (LTBI) has become a major pool of potential active tuberculosis cases and is propelling the TB global health burden further. Objective: The creation and application of a diagnostic to effectively identify LTBI is vital. This systematic review aims to examine and analyze the present and proposed future diagnostics in the identification of latent tuberculosis. Design: Systematic Review Methods: PubMed and Scopus were scanned as primary databases during May 2022. Exclusion criteria for the papers scanned included patients with immunosuppression (due to HIV or treatment), pediatric TB, cancer and dialysis patients, pregnancy, IV drug users, animal models, papers published before 2005, co-infected patients, IBD and transplant patients, and finally secondary literature. Such criteria were incorporated due to the differences in TB immunology in these circumstances. 18 papers were included in this review and their risk of bias assessed using the QUADAS-2 guidelines. For analysis the papers sensitivities and specificities were examined. There was also a deeper look into the surrounding variables such as population differentiation, diagnostic technologies, clinical translation, and bias. Findings: With thorough analysis of the data, it was determined that there are promising diagnostics for the precise identification of LTBI. Specifically, 2 studies one which used ELISA measuring the IgG response of LTBI and ATB patients when exposed to a combination of antigens and this resulted in a sensitivity and specificity of 93.33% and 93.10% respectively. The second study utilizes ESAT-6 SFC MSS (mean spot size) and the modified TBAg/PHA ratio diagnostic model to establish LTBI or ATB and using ROC curve analysis found a sensitivity of 90.12% and specificity of 91.02%. Interpretation: To conclude, specific diagnostics still being examined in the preliminary phase could in the future be used as adjuncts to already present diagnostics for the diagnosis of LTBI based on their strong sensitivities and specificities. No funding.

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“…560485), and the levels of interleukin 2 (IL-2), IL-4, IL-6, IL-10, IFN-γ, IL-17A, and tumor necrosis factor α (TNF-α) were quantified according to our previous studies. [35][36][37]…”

Section: Detection Of Cytokinesmentioning

confidence: 99%

Development and Evaluation of a Promising Biomarker for Diagnosis of Latent and Active Tuberculosis Infection

Peng,

Jiang,

Liu

et al. 2024

Infect Dis Immun

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Background Diagnosing latent tuberculosis (TB) infection (LTBI) and active TB (ATB) is crucial for preventing disease progression and transmission. However, current diagnostic tests have limitations in terms of accuracy and sensitivity, making it challenging to diagnose these different infection states. Therefore, this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic tests. Methods We developed a novel multiepitope-based diagnostic biomarker (MEBDB) from LTBI region of differentiation antigens using bioinformatics and immunoinformatics. Immune responses induced by MEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead assays. This study was conducted from April 2022 to December 2022 in the Senior Department of Tuberculosis at the 8th Medical Center of PLA General Hospital, China. Blood samples were collected from participants with ATB, individuals with LTBI, and healthy controls (HCs). The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic curves. Results A novel MEBDB, designated as CP19128P, was generated. CP19128P comprises 19 helper T lymphocyte epitopes, 12 cytotoxic T lymphocyte epitopes, and 8 B-cell epitopes. In silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune responses. CP19128P generated significantly higher levels of tumor necrosis factor (TNF-α), interleukin 4 (IL-4), and IL-10 in ATB patients (n = 7) and LTBI (n = 8) individuals compared with HCs (n = 62) (P < 0.001). Moreover, CP19128P-induced specific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and specificity. Combining IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs (the area under the receiver operating characteristic curve [AUC], 0.976 [95% confidence interval [CI], 0.934–1.000] or 0.986 [0.956–1.000]), whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from HCs (AUC, 0.887 [0.782–0.993] or 0.984 [0.958–1.000]). Conclusions Our study revealed that CP19128P is a potential MEBDB for the diagnosis of LTBI and ATB. Our findings suggest a promising strategy for developing novel, accurate, and sensitive diagnostic biomarkers and identifying new targets for TB diagnosis and management.

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Prediction of Th1 and Cytotoxic T Lymphocyte Epitopes of Mycobacterium tuberculosis and Evaluation of Their Potential in the Diagnosis of Tuberculosis in a Mouse Model and in Humans

Abstract: Latent tuberculosis infection (LTBI) is a challenging problem in preventing, diagnosing, and treating tuberculosis (TB). The innate and adaptive immune responses are essential for eliminating or killing the mycobacteria.

Cited by 7 publications

References 48 publications

Bioinformatics analysis and consistency verification of a novel tuberculosis vaccine candidate HP13138PB

Bioinformatics analysis and consistency verification of a novel tuberculosis vaccine candidate HP13138PB

Latent Tuberculosis Diagnostics: A Systematic Review What is the past, present, and future in the diagnosis of latent tuberculosis?

Development and Evaluation of a Promising Biomarker for Diagnosis of Latent and Active Tuberculosis Infection

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