Developing a multiepitope vaccine for the prevention of SARS-CoV-2 and monkeypox virus co-infection: A reverse vaccinology analysis

Jiang, Fan; Liu, Yinping; Xue, Yong; Cheng, Ping; Wang, Jie; Lian, Jian-Qi; Gong, Wenping

doi:10.1016/j.intimp.2023.109728

Cited by 19 publications

(21 citation statements)

References 115 publications

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“…The ideal vaccines designed using reverse vaccinology approaches should have good immunogenicity and antigenicity, allowing them to effectively activate both innate and adaptive immune cells [72]. It is also crucial that these vaccines are safe, non‐toxic, and non‐allergenic [13, 33]. Our results demonstrate that the C624P vaccine has acceptable antigenicity and immunogenicity and is non‐toxic and non‐sensitizing, making it a safe MEV candidate.…”

Section: Discussionmentioning

confidence: 86%

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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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Section: Discussionmentioning

confidence: 86%

“…As many B-cell epitopes are discontinuous, we used the ElliPro server (http://tools.iedb.org/ellipro/) to predict potential discontinuous B-cell epitopes of the candidate multi-epitope vaccine (MEV) based on our previous studies [13,33,36,37].…”

Section: Discontinuous B-cell Epitopes Of the Candidate Mevmentioning

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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“…Subsequently, the above mentioned immunodominant HTL or CTL epitopes were screened for antigenicity scores >0.7 and immunogenicity scores >0 using VaxiJen v2.0 (http://www.ddg-pharmfac.net/vaxijen/VaxiJen/VaxiJen.html) and the Class I Immunogenicity Server (http://tools.iedb.org/immunogenicity/) according to our previous studies, respectively. [19,24,25] Then, the level of IFN-γ induced by the HTL epitopes was predicted by the IFN epitope server (http://crdd.osdd.net/raghava/ifnepitope/index.php). [26] As a result, the HTL and CTL epitopes that pass the above hierarchical screening were identified as the candidate immunodominant epitopes for further analysis.…”

Section: Methodsmentioning

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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“…Furthermore, the best model with the highest C-score was selected for optimization using the GalaxyRefine web server (https://galaxy.seoklab.org/cgi-bin/submit.cgi?type=REFINE (accessed on 16 February 2022). Verification of the optimized structure model was confirmed using the ProSA web server (https://prosa.services.came.sbg.ac.at/prosa.php (accessed on 16 February 2022) and the ERRAT server (https://saves.mbi.ucla.edu/ (accessed on 16 February 2022) following our previous studies [8,23,26,27]. Potential protein structure errors were detected using the ProSA web server based on the Z-score, and a Z-score > 0 indicates that there may be an error or unstable part in the protein model.…”

Section: Prediction Of Physicochemical Properties and Secondary/terti...mentioning

confidence: 96%

“…Helper T lymphocyte (HTL) and cytotoxic T lymphocyte (CTL) epitopes were predicted from the selected LTBI-RD antigens using the MHC II server (http://tools.iedb. org/mhcii/ (accessed on 4 February 2022) and MHC I server (http://tools.iedb.org/mhci/ (accessed on 4 February 2022) in the IEDB database, respectively, following our previous studies [8,23,24,26,27]. HTL and CTL epitopes with percentile ranks < 0.5 were considered immunodominant.…”

Section: Screening For Immunodominant T Cell Epitopesmentioning

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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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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Developing a multiepitope vaccine for the prevention of SARS-CoV-2 and monkeypox virus co-infection: A reverse vaccinology analysis

Cited by 19 publications

References 115 publications

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

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

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

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