In silico analysis for the development of multi-epitope vaccines against Mycobacterium tuberculosis
As Bacille Calmette-Guérin (BCG) vaccine’s effectiveness is limited to only children, the development of new tuberculosis (TB) vaccines is being studied using several platforms, and a novel TB vaccine that overcomes this limitation is required. In this study, we designed an effective multi-epitope v...
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| Format: | Article |
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1474346/full |
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| author | Jin-Seung Yun Jin-Seung Yun A Reum Kim Soo Min Kim Eunkyung Shin Sang-Jun Ha Dokeun Kim Hye-Sook Jeong |
| author_facet | Jin-Seung Yun Jin-Seung Yun A Reum Kim Soo Min Kim Eunkyung Shin Sang-Jun Ha Dokeun Kim Hye-Sook Jeong |
| author_sort | Jin-Seung Yun |
| collection | DOAJ |
| description | As Bacille Calmette-Guérin (BCG) vaccine’s effectiveness is limited to only children, the development of new tuberculosis (TB) vaccines is being studied using several platforms, and a novel TB vaccine that overcomes this limitation is required. In this study, we designed an effective multi-epitope vaccine against Mycobacterium tuberculosis using immunoinformatic analysis. First, we selected 11 highly antigenic proteins based on previous research: Ag85A, Ag85B, Ag85C, ESAT-6, MPT64, Rv2660c, TB10.4, HspX, GlfT2, Fas, and IniB. Among these antigens, 10 linear B-cell epitopes, 9 helper T-cell epitopes, and 16 cytotoxic T-cell epitopes were predicted to design the multi-epitope vaccine. To improve the immunogenicity of the candidate vaccine, three different adjuvants, griselimycin, human beta-defensin 3 (HBD3), and 50s ribosomal protein (50sRP), were attached with linker sequences to the vaccine model. The immunogenic, antigenic, allergenic, and physicochemical properties of the resulting designed multi-epitope vaccines were predicted in silico. Moreover, 3D structural modeling, refinement, and validation were used to select a model for further evaluation. Molecular docking analysis revealed a consistent and significant binding affinity of the candidate vaccine for toll-like receptors (TLRs), TLR-2, -3, and -4. Immune simulation performed using C-ImmSim demonstrated that three rounds of immunization with multi-epitope vaccines induced a high production of cytokines and immunoglobulins related with both cellular and humoral immune response. Moreover, we constructed vaccine candidate composed of 50sRP and evaluated its immunogenicity in a mouse model. Consequently, this in silico-engineered multi-epitope structure can elicit adaptive immune responses and represents a promising novel candidate for TB vaccine development. |
| format | Article |
| id | doaj-art-83b9f3d1879944d1ade07dd6cd565341 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-83b9f3d1879944d1ade07dd6cd5653412024-11-18T06:10:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-11-011510.3389/fimmu.2024.14743461474346In silico analysis for the development of multi-epitope vaccines against Mycobacterium tuberculosisJin-Seung Yun0Jin-Seung Yun1A Reum Kim2Soo Min Kim3Eunkyung Shin4Sang-Jun Ha5Dokeun Kim6Hye-Sook Jeong7Korea National Institute of Health, Korea Disease Control and Prevention Agency, CheongJu, Republic of KoreaDepartment of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of KoreaChemicals Research Division, National Institute of Environmental Research, Incheon, Republic of KoreaKorea National Institute of Health, Korea Disease Control and Prevention Agency, CheongJu, Republic of KoreaKorea National Institute of Health, Korea Disease Control and Prevention Agency, CheongJu, Republic of KoreaDepartment of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of KoreaKorea National Institute of Health, Korea Disease Control and Prevention Agency, CheongJu, Republic of KoreaKorea National Institute of Health, Korea Disease Control and Prevention Agency, CheongJu, Republic of KoreaAs Bacille Calmette-Guérin (BCG) vaccine’s effectiveness is limited to only children, the development of new tuberculosis (TB) vaccines is being studied using several platforms, and a novel TB vaccine that overcomes this limitation is required. In this study, we designed an effective multi-epitope vaccine against Mycobacterium tuberculosis using immunoinformatic analysis. First, we selected 11 highly antigenic proteins based on previous research: Ag85A, Ag85B, Ag85C, ESAT-6, MPT64, Rv2660c, TB10.4, HspX, GlfT2, Fas, and IniB. Among these antigens, 10 linear B-cell epitopes, 9 helper T-cell epitopes, and 16 cytotoxic T-cell epitopes were predicted to design the multi-epitope vaccine. To improve the immunogenicity of the candidate vaccine, three different adjuvants, griselimycin, human beta-defensin 3 (HBD3), and 50s ribosomal protein (50sRP), were attached with linker sequences to the vaccine model. The immunogenic, antigenic, allergenic, and physicochemical properties of the resulting designed multi-epitope vaccines were predicted in silico. Moreover, 3D structural modeling, refinement, and validation were used to select a model for further evaluation. Molecular docking analysis revealed a consistent and significant binding affinity of the candidate vaccine for toll-like receptors (TLRs), TLR-2, -3, and -4. Immune simulation performed using C-ImmSim demonstrated that three rounds of immunization with multi-epitope vaccines induced a high production of cytokines and immunoglobulins related with both cellular and humoral immune response. Moreover, we constructed vaccine candidate composed of 50sRP and evaluated its immunogenicity in a mouse model. Consequently, this in silico-engineered multi-epitope structure can elicit adaptive immune responses and represents a promising novel candidate for TB vaccine development.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1474346/fulltuberculosis (TB)peptide-based vaccineimmunoinformatics analysismulti-epitopeadjuvanted vaccine |
| spellingShingle | Jin-Seung Yun Jin-Seung Yun A Reum Kim Soo Min Kim Eunkyung Shin Sang-Jun Ha Dokeun Kim Hye-Sook Jeong In silico analysis for the development of multi-epitope vaccines against Mycobacterium tuberculosis Frontiers in Immunology tuberculosis (TB) peptide-based vaccine immunoinformatics analysis multi-epitope adjuvanted vaccine |
| title | In silico analysis for the development of multi-epitope vaccines against Mycobacterium tuberculosis |
| title_full | In silico analysis for the development of multi-epitope vaccines against Mycobacterium tuberculosis |
| title_fullStr | In silico analysis for the development of multi-epitope vaccines against Mycobacterium tuberculosis |
| title_full_unstemmed | In silico analysis for the development of multi-epitope vaccines against Mycobacterium tuberculosis |
| title_short | In silico analysis for the development of multi-epitope vaccines against Mycobacterium tuberculosis |
| title_sort | in silico analysis for the development of multi epitope vaccines against mycobacterium tuberculosis |
| topic | tuberculosis (TB) peptide-based vaccine immunoinformatics analysis multi-epitope adjuvanted vaccine |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1474346/full |
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