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  • 1
    Online Resource
    Online Resource
    RNA-seq Analysis of the BCG Vaccine in a Humanized Mouse Model
    Compuscript, Ltd. ; 2023
    In:  Zoonoses Vol. 3, No. 1 ( 2023-01-03)
    Details
    In: Zoonoses, Compuscript, Ltd., Vol. 3, No. 1 ( 2023-01-03)
    Abstract: This study was aimed at screening differentially expressed genes (DEGs) and exploring the potential immune mechanism induced by the Bacillus Calmette-Guerin (BCG) vaccine in a humanized mouse model. Methods: Candidate DEGs between mice vaccinated with BCG or injected with PBS were identified through transcriptomics, and their biological functions, signaling pathways, and protein interaction networks were analyzed through bioinformatics. Results: A total of 1035 DEGs were identified by transcriptomics: 398 up-regulated and 637 down-regulated. GO analysis indicated that these DEGs were significantly enriched in cell adhesion, oxygen transport, receptor complex, carbohydrate binding, serine-type endopeptidase activity, and peroxidase activity terms. KEGG analysis indicated that these DEGs were involved in the Rap1 signaling pathway, axon guidance, PI3K-Akt signaling pathway, natural killer cell mediated cytotoxicity, and cytokine-cytokine receptor interaction. Protein interaction network analysis demonstrated that the Myc, Vegfa, and Itgb3 proteins had the highest aggregation degree, aggregation coefficient, and connectivity. Conclusion: The BCG vaccine induced 1035 DEGs in humanized mice. Among them, the differentially expressed down-regulated genes myc and itgb3 involved in the PI3K-Akt signaling pathway may play essential roles in the immune mechanism of the BCG vaccine.
    Type of Medium: Online Resource
    ISSN: 2737-7466 , 2737-7474
    URL: Article
    DOI: 10.15212/ZOONOSES-2022-0035
    Language: English
    Publisher: Compuscript, Ltd.
    Publication Date: 2023
    detail.hit.zdb_id: 3164470-3
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  • 2
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    Verapamil Regulates the Macrophage Immunity to Mycobacterium tuberculosis through NF-κB Signaling
    Bentham Science Publishers Ltd. ; 2023
    In:  Current Molecular Medicine Vol. 23, No. 6 ( 2023-07), p. 536-549
    Details
    In: Current Molecular Medicine, Bentham Science Publishers Ltd., Vol. 23, No. 6 ( 2023-07), p. 536-549
    Abstract: Verapamil enhances the sensitivity of Mycobacterium tuberculosis to anti-tuberculosis (TB) drugs, promotes the macrophage anti-TB ability, and reduces drug resistance, but its mechanism is unclear. Herein, we have investigated the effect of verapamil on cytokine expression in mouse peritoneal macrophages. Methods: Macrophages from mice infected with M. tuberculosis or S. aureus were cultured with verapamil, the cytokines were detected by enzyme-linked immunosorbent assay, and the RNA was measured with quantitative real-time polymerase chain reaction and agarose gel electrophoresis. The intracellular calcium signaling was measured by confocal microscopy. Results: Significantly higher levels of NF-κB, IL-12, TNF-α, and IL-1β were observed after TB infection. The levels of NF-κB and IL-12 increased when verapamil concentration was less than 50 μg/ml, but decreased when verapamil concentration was greater than 50μg/ml. With the increase in verapamil concentration, TNF-α and IL-1β expressed by macrophages decreased. The L-type calcium channel transcription significantly increased in M. tuberculosis rather than S. aureus-infected macrophages. Furthermore, during bacillus Calmette-Guerin (BCG) infection, verapamil stimulated a sharp peak in calcium concentration in macrophages, while calcium concentration increased mildly and decreased smoothly over time in the absence of verapamil. Conclusions: Verapamil enhanced macrophage immunity via the NF-κB pathway, and its effects on cytokine expression may be achieved by its regulation of intracellular calcium signaling.
    Type of Medium: Online Resource
    ISSN: 1566-5240
    URL: Article
    DOI: 10.2174/1566524022666220513092244
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2023
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  • 3
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    Immunogenicity and Therapeutic Effects of Latency-Associated Genes in a Mycobacterium Tuberculosis Reactivation Mouse Model
    Mary Ann Liebert Inc ; 2019
    In:  Human Gene Therapy Methods Vol. 30, No. 2 ( 2019-04), p. 60-69
    Details
    In: Human Gene Therapy Methods, Mary Ann Liebert Inc, Vol. 30, No. 2 ( 2019-04), p. 60-69
    Type of Medium: Online Resource
    ISSN: 1946-6536 , 1946-6544
    URL: Article
    DOI: 10.1089/hgtb.2018.211
    Language: English
    Publisher: Mary Ann Liebert Inc
    Publication Date: 2019
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  • 4
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    Table_1.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-1-31)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-1-31)
    Abstract: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis . As a result of the coronavirus disease 2019 (COVID-19) pandemic, the global TB mortality rate in 2020 is rising, making TB prevention and control more challenging. Vaccination has been considered the best approach to reduce the TB burden. Unfortunately, BCG, the only TB vaccine currently approved for use, offers some protection against childhood TB but is less effective in adults. Therefore, it is urgent to develop new TB vaccines that are more effective than BCG. Accumulating data indicated that peptides or epitopes play essential roles in bridging innate and adaptive immunity and triggering adaptive immunity. Furthermore, innovations in bioinformatics, immunoinformatics, synthetic technologies, new materials, and transgenic animal models have put wings on the research of peptide-based vaccines for TB. Hence, this review seeks to give an overview of current tools that can be used to design a peptide-based vaccine, the research status of peptide-based vaccines for TB, protein-based bacterial vaccine delivery systems, and animal models for the peptide-based vaccines. These explorations will provide approaches and strategies for developing safer and more effective peptide-based vaccines and contribute to achieving the WHO’s End TB Strategy.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.830497
    DOI: 10.3389/fimmu.2022.830497.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 5
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    Table_3.doc
    Frontiers Media SA ; 2022
    In:  Frontiers in Cellular and Infection Microbiology Vol. 12 ( 2022-11-2)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 12 ( 2022-11-2)
    Abstract: Our previous study developed a novel peptide-based vaccine, MP3RT, to fight against tuberculosis (TB) infection in a mouse model. However, the consistency between the immunoinformatics predictions and the results of real-world animal experiments on the MP3RT vaccine remains unclear. Method In this study, we predicted the antigenicity, immunogenicity, physicochemical parameters, secondary structure, and tertiary structure of MP3RT using bioinformatics technologies. The immune response properties of the MP3RT vaccine were then predicted using the C-ImmSim server. Finally, humanized mice were used to verify the characteristics of the humoral and cellular immune responses induced by the MP3RT vaccine. Results MP3RT is a non-toxic and non-allergenic vaccine with an antigenicity index of 0.88 and an immunogenicity index of 0.61, respectively. Our results showed that the MP3RT vaccine contained 53.36% α-helix in the secondary structure, and the favored region accounted for 98.22% in the optimized tertiary structure. The binding affinities of the MP3RT vaccine to the human leukocyte antigen (HLA)-DRB1*01:01 allele, toll-like receptor-2 (TLR-2), and TLR-4 receptors were -1234.1 kcal/mol, -1066.4 kcal/mol, and -1250.4 kcal/mol, respectively. The results of the C-ImmSim server showed that the MP3RT vaccine could stimulate T and B cells to produce immune responses, such as high levels of IgM and IgG antibodies, IFN-γ, TNF-α, and IL-2 cytokines. Results from real-world animal experiments showed that the MP3RT vaccine could stimulate the humanized mice to produce high levels of IgG and IgG2a antibodies and IFN-γ + T lymphocytes. Furthermore, the levels of IFN-γ, IL-2, and IL-6 cytokines in mice immunized with the MP3RT vaccine were significantly higher than those in the control group. Conclusion MP3RT is a highly antigenic and immunogenic potential vaccine that can effectively induce Th1-type immune responses in silico analysis and animal experiments. This study lays the foundation for evaluating the value of computational tools and immunoinformatic techniques in reverse vaccinology research.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fcimb.2022.1047306
    DOI: 10.3389/fcimb.2022.1047306.s001
    DOI: 10.3389/fcimb.2022.1047306.s002
    DOI: 10.3389/fcimb.2022.1047306.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2619676-1
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  • 6
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    A Summary on Tuberculosis Vaccine Development—Where to Go?
    MDPI AG ; 2023
    In:  Journal of Personalized Medicine Vol. 13, No. 3 ( 2023-02-24), p. 408-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 13, No. 3 ( 2023-02-24), p. 408-
    Abstract: Background: Tuberculosis (TB) is an old infectious disease caused by Mycobacterium tuberculosis infection. Vaccination is the most effective way to prevent and control TB. However, there is relatively little literature that systematically analyzes the progress of new TB vaccine research from a bibliometric perspective. This study was conducted to examine the development of TB vaccines over the past 20 years and to identify research priorities and directions for the future. Methods: The Science Citation Index Expanded (SCI-E) of the Web of Science Core Collection (WOSCC) database was selected to search the literature related to TB vaccines. The countries, institutions, authors, journals, references, and keywords of each publication were analyzed and visualized using the VOSviewer, CiteSpace, and Bibliometrix software. Furthermore, GraphPad Prism and Microsoft Excel 365 were also used for statistical analysis. Results: As of 20 October 2022, 7960 publications related to TB vaccines were identified with 288,478 citations. The United States of America (USA) accounted for the largest share (2658, 33.40%), followed by the United Kingdom (UK, 1301, 16.34%), and China (685, 8.6%). Regarding affiliations, the University of London had the most publications (427) and shared the highest H-index (76) with the Statens Serum Institut of Denmark. In terms of the number of articles for the journals and authors, the journal Vaccine ranked first with 629 articles. Professor Peter Anderssen has published the highest number of papers (160). The burst keywords and thematic maps analysis showed that future trends in TB vaccine development would focus on exploring the interaction mechanisms between M. tuberculosis and the host. Conclusion: The number of publications on TB vaccines has grown over the past two decades. Developed countries play a significant role in TB vaccine research, and developing countries are fast catching up. We believe that future research will be aimed at understanding the fine molecular mechanisms of host–pathogen interaction, leading to the development of better TB vaccines.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm13030408
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662248-8
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  • 7
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    Table_1.xls
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-4-26)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-4-26)
    Abstract: Tuberculosis (TB) is still a global infectious disease that seriously threatens human beings. The only licensed TB vaccine Bacille Calmette-Guérin (BCG)’s protective efficacy varies significantly among populations and regions. It is very urgent to develop more effective vaccines. Methods In this study, eleven candidate proteins of Mycobacterium tuberculosis were selected to predict peptides with high-affinity binding capacity for the HLA-DRB1*01:01 molecule. The immunodominant peptides were identified with the enzyme-linked immunospot assay (ELISPOT) and linked in silico to result in a novel polypeptide vaccine in Escherichia coli cells. The vaccine’s protective efficacy was evaluated in humanized and wild-type C57BL/6 mice. The potential immune protective mechanisms were explored with Enzyme-linked Immunosorbent Assay (ELISA), flow cytometry, and ELISPOT. Results Six immunodominant peptides screened from 50 predicted peptides were used to construct a new polypeptide vaccine named MP3RT. After challenge with M. tuberculosis , the colony-forming units (CFUs), lung lesion area, and the number of inflammatory cells in humanized mice rather than wild-type mice vaccinated with MP3RT were significantly lower than these in mice immunized with PBS. The humanized mice vaccinated with MP3RT revealed significant increases in IFN-γ cytokine production, IFN-γ + T lymphocytes, CD3 + IFN-γ + T lymphocytes, and the MP3RT-specific IgG antibody. Conclusions Taken together, MP3RT is a promising peptides-based TB vaccine characterized by inducing high levels of IFN-γ and CD3 + IFN-γ + T lymphocytes in humanized mice. These new findings will lay a foundation for the development of peptides-based vaccines against TB.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.666290
    DOI: 10.3389/fimmu.2021.666290.s001
    DOI: 10.3389/fimmu.2021.666290.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 8
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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
    American Society for Microbiology ; 2022
    In:  Microbiology Spectrum Vol. 10, No. 4 ( 2022-08-31)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 10, No. 4 ( 2022-08-31)
    Abstract: Latent tuberculosis infection (LTBI) is the primary source of tuberculosis (TB) but there is no suitable detection method to distinguish LTBI from active tuberculosis (ATB). In this study, five antigens of Mycobacterium tuberculosis belonging to LTBI and regions of difference (RDs) were selected to predict Th1 and cytotoxic T lymphocyte (CTL) epitopes. The immunodominant Th1 and CTL peptides were identified in mouse models, and their performance in distinguishing LTBI from ATB was determined in mice and humans. Ten Th1 and ten CTL immunodominant peptides were predicted and synthesized in vitro . The enzyme-linked immunosorbent spot assay results showed that the combination of five Th1 peptides (area under the curve [AUC] = 1, P  〈   0.0001; sensitivity = 100% and specificity = 93.33%), the combination of seven CTL peptides (AUC = 1, P  〈   0.0001; 100 and 95.24%), and the combination of four peptide pools (AUC = 1, P  〈   0.0001; sensitivity = 100% and specificity = 91.67%) could significantly discriminate mice with LTBI from mice with ATB or uninfected controls (UCs). The combined peptides or peptide pools induced significantly different cytokine levels between the three groups, improving their ability to differentiate ATB from LTBI. Furthermore, it was found that pool 2 could distinguish patients with ATB from UCs (AUC = 0.6728, P =  0.0041; sensitivity = 72.58% and specificity = 59.46%). The combination of Th1 and CTL immunodominant peptides derived from LTBI-RD antigens might be a promising strategy for diagnosing ATB and LTBI in mice and patients with ATB and uninfected controls. IMPORTANCE 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. Antigen-presenting cells (APCs) present and display mycobacterium peptides on their surfaces, and recognition between T cells and APCs is based on some essential peptides rather than the full-length protein. Therefore, the selection of candidate antigens and the prediction and screening of potential immunodominant peptides have become a key to designing a new generation of TB diagnostic biomarkers. This study is the first to report that the combination of Th1 and CTL immunodominant peptides derived from LTBI-RD antigens can distinguish LTBI from active TB (ATB) in animals and ATB patients from uninfected individuals. These findings provide a novel insight for discovering potential biomarkers for the differential diagnosis of ATB and LTBI in the future.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.01438-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2807133-5
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  • 9
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    A peptide-based vaccine ACP derived from antigens of Mycobacterium tuberculosis induced Th1 response but failed to enhance the protective efficacy of BCG in mice
    Elsevier BV ; 2022
    In:  Indian Journal of Tuberculosis Vol. 69, No. 4 ( 2022-10), p. 482-495
    Details
    In: Indian Journal of Tuberculosis, Elsevier BV, Vol. 69, No. 4 ( 2022-10), p. 482-495
    Type of Medium: Online Resource
    ISSN: 0019-5707
    URL: Article
    DOI: 10.1016/j.ijtb.2021.08.016
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2164411-1
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  • 10
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    PP19128R, a Multiepitope Vaccine Designed to Prevent Latent Tuberculosis Infection, Induced Immune Responses In Silico and In Vitro Assays
    MDPI AG ; 2023
    In:  Vaccines Vol. 11, No. 4 ( 2023-04-17), p. 856-
    Details
    In: Vaccines, MDPI AG, Vol. 11, No. 4 ( 2023-04-17), p. 856-
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    URL: Article
    DOI: 10.3390/vaccines11040856
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2703319-3
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