In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection

BackgroundLatent tuberculosis infection (LTBI) is the primary source of active tuberculosis (ATB), but there are no specific methods for diagnosing and preventing LTBI.MethodsDominant T and B cell epitopes predicted from five antigens related to LTBI and Mycobacterium tuberculosis region of differen...

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Main Authors: Peng Cheng, Liang Wang, Wenping Gong
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2022.947852/full
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author Peng Cheng
Peng Cheng
Liang Wang
Wenping Gong
author_facet Peng Cheng
Peng Cheng
Liang Wang
Wenping Gong
author_sort Peng Cheng
collection DOAJ
description BackgroundLatent tuberculosis infection (LTBI) is the primary source of active tuberculosis (ATB), but there are no specific methods for diagnosing and preventing LTBI.MethodsDominant T and B cell epitopes predicted from five antigens related to LTBI and Mycobacterium tuberculosis region of difference (LTBI-RD) were used to construct a novel polypeptide molecule (PPM). Then, the physicochemical properties, secondary structure, tertiary structure of the PPM, and its binding ability to toll-like receptor 2 (TLR2) and TLR4 were analyzed by bioinformatics tools. Finally, immune stimulation and expression optimization of the PPM were carried out.ResultsFour helper T lymphocytes (HTL) epitopes, five cytotoxic T lymphocytes (CTL) epitopes, and three B cell epitopes were predicted and screened from five LTBI-RD related antigens. These epitopes were connected in series with linkers and adjuvants to construct a novel PPM termed C543P. The results indicated that antigenicity and immunogenicity scores of the C543P candidate were 0.936399 and 1.36469, respectively. The structural analysis results showed that the C543P candidate had good stability. Its secondary structure contained 43.6% α-helix, the Z-score after tertiary structure optimization was −7.9, and the Ramachandran diagram showed that 88.77% amino acid residues of the C543P candidate were in the allowable region. Furthermore, the C543P candidate showed an excellent affinity to TLR2 (−1091.7kcal/mol) and TLR4 (−1102.7kcal/mol). In addition, we also analyzed the immunological characteristics of the C543P candidate. Immune stimulation prediction showed that the C543P candidate could effectively activate T and B lymphocytes and produce high levels of Th1 cytokines such as IFN-γ and IL-2.ConclusionWe constructed a novel PPM with acceptable antigenicity, immunogenicity, stability, and ability to induce robust immune responses. This study provides a new diagnostic biomarker or peptides-based vaccine for LTBI diagnosis and prevention.
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spelling doaj.art-eeda21bf0d984024a26f090536b768b52022-12-22T02:33:38ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-06-011310.3389/fmicb.2022.947852947852In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis InfectionPeng Cheng0Peng Cheng1Liang Wang2Wenping Gong3Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing, ChinaHebei North University, Zhangjiakou, ChinaDepartment of Geriatrics, The 8th Medical Center of PLA General Hospital, Beijing, ChinaTuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing, ChinaBackgroundLatent tuberculosis infection (LTBI) is the primary source of active tuberculosis (ATB), but there are no specific methods for diagnosing and preventing LTBI.MethodsDominant T and B cell epitopes predicted from five antigens related to LTBI and Mycobacterium tuberculosis region of difference (LTBI-RD) were used to construct a novel polypeptide molecule (PPM). Then, the physicochemical properties, secondary structure, tertiary structure of the PPM, and its binding ability to toll-like receptor 2 (TLR2) and TLR4 were analyzed by bioinformatics tools. Finally, immune stimulation and expression optimization of the PPM were carried out.ResultsFour helper T lymphocytes (HTL) epitopes, five cytotoxic T lymphocytes (CTL) epitopes, and three B cell epitopes were predicted and screened from five LTBI-RD related antigens. These epitopes were connected in series with linkers and adjuvants to construct a novel PPM termed C543P. The results indicated that antigenicity and immunogenicity scores of the C543P candidate were 0.936399 and 1.36469, respectively. The structural analysis results showed that the C543P candidate had good stability. Its secondary structure contained 43.6% α-helix, the Z-score after tertiary structure optimization was −7.9, and the Ramachandran diagram showed that 88.77% amino acid residues of the C543P candidate were in the allowable region. Furthermore, the C543P candidate showed an excellent affinity to TLR2 (−1091.7kcal/mol) and TLR4 (−1102.7kcal/mol). In addition, we also analyzed the immunological characteristics of the C543P candidate. Immune stimulation prediction showed that the C543P candidate could effectively activate T and B lymphocytes and produce high levels of Th1 cytokines such as IFN-γ and IL-2.ConclusionWe constructed a novel PPM with acceptable antigenicity, immunogenicity, stability, and ability to induce robust immune responses. This study provides a new diagnostic biomarker or peptides-based vaccine for LTBI diagnosis and prevention.https://www.frontiersin.org/articles/10.3389/fmicb.2022.947852/fulltuberculosis (TB)latent tuberculosis infection (LTBI)biomarkervaccinediagnosis
spellingShingle Peng Cheng
Peng Cheng
Liang Wang
Wenping Gong
In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection
Frontiers in Microbiology
tuberculosis (TB)
latent tuberculosis infection (LTBI)
biomarker
vaccine
diagnosis
title In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection
title_full In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection
title_fullStr In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection
title_full_unstemmed In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection
title_short In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection
title_sort in silico analysis of peptide based biomarkers for the diagnosis and prevention of latent tuberculosis infection
topic tuberculosis (TB)
latent tuberculosis infection (LTBI)
biomarker
vaccine
diagnosis
url https://www.frontiersin.org/articles/10.3389/fmicb.2022.947852/full
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