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

Cheng, Ping; Jiang, Fan; Wang, Guiyuan; Wang, Jie; Xue, Yong; Wang, Liang; Gong, Wenping

doi:10.3389/fimmu.2023.1102578

Cited by 16 publications

(20 citation statements)

References 68 publications

(76 reference statements)

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“…CD8 + T cells and B cells have been reported to be important in eliminating and killing MTB [4,8,23,51]. In another previous study, we developed an MEV named HP13138PB against MTB infection in silico and verified its immunological properties in in vitro experiments [49]. However, the HP13138PB vaccine was designed with the addition of TLR2 agonist PSMα4 but not TLR4 agonist, so its immunogenicity was not further enhanced.…”

Section: Discussionmentioning

confidence: 98%

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PP19128R, a Multiepitope Vaccine Designed to Prevent Latent Tuberculosis Infection, Induced Immune Responses In Silico and In Vitro Assays

et al. 2023

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Background: Latent tuberculosis infection (LTBI) is the primary source of active tuberculosis (ATB), but a preventive vaccine against LTBI is lacking. Methods: In this study, dominant helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL), and B-cell epitopes were identified from nine antigens related to LTBI and regions of difference (RDs). These epitopes were used to construct a novel multiepitope vaccine (MEV) based on their antigenicity, immunogenicity, sensitization, and toxicity. The immunological characteristics of the MEV were analyzed with immunoinformatics technology and verified by enzyme-linked immunospot assay and Th1/Th2/Th17 cytokine assay in vitro. Results: A novel MEV, designated PP19128R, containing 19 HTL epitopes, 12 CTL epitopes, 8 B-cell epitopes, toll-like receptor (TLR) agonists, and helper peptides, was successfully constructed. Bioinformatics analysis showed that the antigenicity, immunogenicity, and solubility of PP19128R were 0.8067, 9.29811, and 0.900675, respectively. The global population coverage of PP19128R in HLA class I and II alleles reached 82.24% and 93.71%, respectively. The binding energies of the PP19128R-TLR2 and PP19128R-TLR4 complexes were −1324.77 kcal/mol and −1278 kcal/mol, respectively. In vitro experiments showed that the PP19128R vaccine significantly increased the number of interferon gamma-positive (IFN-γ+) T lymphocytes and the levels of cytokines, such as IFN-γ, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10. Furthermore, positive correlations were observed between PP19128R-specific cytokines in ATB patients and individuals with LTBI. Conclusions: The PP19128R vaccine is a promising MEV with excellent antigenicity and immunogenicity and no toxicity or sensitization that can induce robust immune responses in silico and in vitro. This study provides a vaccine candidate for the prevention of LTBI in the future.

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Section: Discussionmentioning

confidence: 98%

“…The numbers of IFN-γ+ T lymphocytes induced by the PP19128R vaccine and our previously developed TB vaccine HP13138PB [49] were determined using an ELISpot assay. First, a 5 mL blood sample was collected from HCs (n = 21), LTBI individuals (n = 25), and ATB patients (n = 19).…”

Section: Elispotmentioning

confidence: 99%

PP19128R, a Multiepitope Vaccine Designed to Prevent Latent Tuberculosis Infection, Induced Immune Responses In Silico and In Vitro Assays

et al. 2023

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“…The antigenic protectiveness of the epitopes was predicted using the automatic cross-covariance (ACC) method. We assessed the ability of the identified HTL epitopes to stimulate interferon-γ (IFN-γ) production using the IFN-γ epitope server (http://crdd.osdd.net/raghava/ ifnepitope/index.php), in line with previous reports [34,36]. Only those HTL epitopes with excellent immunogenicity, antigenicity, and ability to induce IFN-γ secretion in human immune cells were retained for constructing the MEV.…”

Section: Htl Epitopesmentioning

confidence: 98%

“…To identify potentially immunodominant HTL epitopes, we utilized the major histocompatibility complex (MHC) II submodule in the Immune Epitope Database (IEDB) (http://tools.iedb.org/mhcii/) as previously reported [13,[32][33][34]. We used IEDB Recommendation 2.22 to predict 15-amino-acid-long HTL epitopes based on a complete human leukocyte antigen (HLA) reference.…”

Section: Htl Epitopesmentioning

confidence: 99%

Design and development of a multi‐epitope vaccine for the prevention of latent tuberculosis infection

Jiang,

Wang,

Wang

et al. 2023

Medicine Advances

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BackgroundLatent tuberculosis infection (LTBI) often progresses to active tuberculosis, necessitating the development of novel vaccine to prevent LTBI. In this study, we aimed to design a Mycobacterium tuberculosis (M. tuberculosis) vaccine that could elicit a potent immune response to prevent LTBI.MethodsWe used bioinformatics and immunoinformatics techniques to develop a multi‐epitope vaccine (MEV) called C624P. The vaccine contained six cytotoxic T lymphocytes (CTL), two helper T lymphocytes (HTL), and four B‐cell epitopes derived from six antigens associated with LTBI and the Mycobacterium tuberculosis region of difference. We added Toll‐like receptor (TLR) agonists and PADRE peptide to the MEV to enhance its immunogenicity. We then analyzed the C624P vaccine's physical and chemical properties, spatial structure, molecular docking with TLRs, and immunological features.ResultsThe C624P vaccine displayed good antigenicity and immunogenicity scores of 0.901398 and 3.65609, respectively. The vaccine structure was stable, with 42.82% α‐helix content, a Z‐value of −7.84, and a favored Ramachandran plot area of 85.84% after majorization. Molecular docking analysis showed that the C624P vaccine could bind tightly to TLR2 (−1011.0 kcal/mol) and TLR4 (−941.4 kcal/mol). Furthermore, the C624P vaccine effectively stimulated T and B lymphocytes, resulting in high levels of Th1 cytokines such as IFN‐γ and IL‐2.ConclusionsThe C624P vaccine represents a promising MEV for preventing LTBI. The vaccine's good antigenicity, immunogenicity, stability, and ability to activate immune responses suggest its effectiveness in preventing LTBI. Our study demonstrated the utility of bioinformatics and immunoinformatics techniques in designing safe and effective tuberculosis vaccines.

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“…In addition, the immunogenicity, toxicity, sensitization, and antigenicity of the constructed MEBDB were predicted by the class I immunogenicity in the IEDB database, Toxin Pred Server, Allergen FP v.1.0 and AllerTOP v.2.0, and the VaxiJen v2.0 following our previous studies, respectively. [19,29] Then, the physicochemical properties of the MEBDB were predicted using the Expasy Protparam server (https://web.expasy.org/protparam/). This server can indicate the physicochemical properties of a candidate, such as the theoretical isoelectric point (PI), molecular weight, aliphatic index, instability, amino acid composition, GRAVY, and the full average of in vivo and in vitro half-life.…”

Section: Construction Of Mebdb and Analysis Of Its Physicochemical Pr...mentioning

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

Cited by 16 publications

References 68 publications

PP19128R, a Multiepitope Vaccine Designed to Prevent Latent Tuberculosis Infection, Induced Immune Responses In Silico and In Vitro Assays

PP19128R, a Multiepitope Vaccine Designed to Prevent Latent Tuberculosis Infection, Induced Immune Responses In Silico and In Vitro Assays

Design and development of a multi‐epitope vaccine for the prevention of latent tuberculosis infection

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

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