Immunoinformatics design of a multi-epitope vaccine for Chlamydia trachomatis major outer membrane proteins
Abstract Chlamydia trachomatis (CT) remains a significant infectious cause of blindness and sexually transmitted infections worldwide. The objective and novelty of this study lie in using different serovars of CT to design a broad-spectrum multi-epitope vaccine that might confer immunity against dif...
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Nature Portfolio
2024-12-01
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| Online Access: | https://doi.org/10.1038/s41598-024-81736-w |
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| author | Seema Shetty Swagatika Dash Avinash Kumar Shashidhar Vishwanath Suvarna G. Kini Angela Brand |
| author_facet | Seema Shetty Swagatika Dash Avinash Kumar Shashidhar Vishwanath Suvarna G. Kini Angela Brand |
| author_sort | Seema Shetty |
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| description | Abstract Chlamydia trachomatis (CT) remains a significant infectious cause of blindness and sexually transmitted infections worldwide. The objective and novelty of this study lie in using different serovars of CT to design a broad-spectrum multi-epitope vaccine that might confer immunity against different CT infections. As the major outer membrane protein in CT has good immunodominance properties and high conservation and also determines the several serotypes of CT, it is selected as an antibody target in this study. T-cell and B-cell epitopes from serovars A, B, D, E, L1, and L2 were predicted and combined into a single construct by incorporating adjuvants and linkers to enhance immunogenicity and stability. Physicochemical characterization confirmed the constructed vaccine’s anti-allergic, immunogenicity, and thermostable characteristics, followed by structural modeling to refine its 3D configuration. The 3D model structure of the vaccine was validated through the Ramachandran plot and ProSA z-score. Molecular docking studies of the vaccine demonstrated stable binding with toll-like receptor 3, along with molecular dynamics simulations and binding free energy calculations supporting the complex’s stability. In silico cloning has indicated a high potential for expression in Escherichia coli. Lastly, immune simulations revealed robust activation of B cells, cytotoxic T cells, and antigen-presenting cells, alongside significant production of IgM, IgG antibodies, and balanced Th1/Th2 cytokine response, which is crucial for effective immunity. These results suggest the multi-epitope vaccine could effectively induce comprehensive immune responses against CT, highlighting the need for further in vivo validation to advance this promising candidate toward clinical use. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-bd5b69d6b9d1443e9e1942e9f7bd01172024-12-08T12:27:22ZengNature PortfolioScientific Reports2045-23222024-12-0114111810.1038/s41598-024-81736-wImmunoinformatics design of a multi-epitope vaccine for Chlamydia trachomatis major outer membrane proteinsSeema Shetty0Swagatika Dash1Avinash Kumar2Shashidhar Vishwanath3Suvarna G. Kini4Angela Brand5Department of Microbiology, Kasturba Medical College, Manipal,, Manipal Academy of Higher EducationDepartment of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher EducationDepartment of Medical Affairs, Curie Sciences Private LimitedDepartment of Microbiology, Kasturba Medical College, Manipal,, Manipal Academy of Higher EducationDepartment of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher EducationFaculty of Health, Medicine and Life Sciences, Maastricht UniversityAbstract Chlamydia trachomatis (CT) remains a significant infectious cause of blindness and sexually transmitted infections worldwide. The objective and novelty of this study lie in using different serovars of CT to design a broad-spectrum multi-epitope vaccine that might confer immunity against different CT infections. As the major outer membrane protein in CT has good immunodominance properties and high conservation and also determines the several serotypes of CT, it is selected as an antibody target in this study. T-cell and B-cell epitopes from serovars A, B, D, E, L1, and L2 were predicted and combined into a single construct by incorporating adjuvants and linkers to enhance immunogenicity and stability. Physicochemical characterization confirmed the constructed vaccine’s anti-allergic, immunogenicity, and thermostable characteristics, followed by structural modeling to refine its 3D configuration. The 3D model structure of the vaccine was validated through the Ramachandran plot and ProSA z-score. Molecular docking studies of the vaccine demonstrated stable binding with toll-like receptor 3, along with molecular dynamics simulations and binding free energy calculations supporting the complex’s stability. In silico cloning has indicated a high potential for expression in Escherichia coli. Lastly, immune simulations revealed robust activation of B cells, cytotoxic T cells, and antigen-presenting cells, alongside significant production of IgM, IgG antibodies, and balanced Th1/Th2 cytokine response, which is crucial for effective immunity. These results suggest the multi-epitope vaccine could effectively induce comprehensive immune responses against CT, highlighting the need for further in vivo validation to advance this promising candidate toward clinical use.https://doi.org/10.1038/s41598-024-81736-wMulti-epitope vaccineChlamydia trachomatisImmunoinformaticsT-cell and B-cell epitopesMolecular dynamics simulationsImmune simulation |
| spellingShingle | Seema Shetty Swagatika Dash Avinash Kumar Shashidhar Vishwanath Suvarna G. Kini Angela Brand Immunoinformatics design of a multi-epitope vaccine for Chlamydia trachomatis major outer membrane proteins Scientific Reports Multi-epitope vaccine Chlamydia trachomatis Immunoinformatics T-cell and B-cell epitopes Molecular dynamics simulations Immune simulation |
| title | Immunoinformatics design of a multi-epitope vaccine for Chlamydia trachomatis major outer membrane proteins |
| title_full | Immunoinformatics design of a multi-epitope vaccine for Chlamydia trachomatis major outer membrane proteins |
| title_fullStr | Immunoinformatics design of a multi-epitope vaccine for Chlamydia trachomatis major outer membrane proteins |
| title_full_unstemmed | Immunoinformatics design of a multi-epitope vaccine for Chlamydia trachomatis major outer membrane proteins |
| title_short | Immunoinformatics design of a multi-epitope vaccine for Chlamydia trachomatis major outer membrane proteins |
| title_sort | immunoinformatics design of a multi epitope vaccine for chlamydia trachomatis major outer membrane proteins |
| topic | Multi-epitope vaccine Chlamydia trachomatis Immunoinformatics T-cell and B-cell epitopes Molecular dynamics simulations Immune simulation |
| url | https://doi.org/10.1038/s41598-024-81736-w |
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