Designing a broad-spectrum multi-epitope subunit vaccine against leptospirosis using immunoinformatics and structural approaches
IntroductionLeptospirosis, caused by Leptospira interrogans, is a neglected zoonotic disease that poses a significant global health risk to both humans and animals. The rise of antimicrobial resistance and the inefficacy of existing vaccines highlight the urgent need for new preventive strategies.Me...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1503853/full |
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| author | Guneswar Sethi Guneswar Sethi Young Kyu Kim Su-Cheol Han Jeong Ho Hwang Jeong Ho Hwang |
| author_facet | Guneswar Sethi Guneswar Sethi Young Kyu Kim Su-Cheol Han Jeong Ho Hwang Jeong Ho Hwang |
| author_sort | Guneswar Sethi |
| collection | DOAJ |
| description | IntroductionLeptospirosis, caused by Leptospira interrogans, is a neglected zoonotic disease that poses a significant global health risk to both humans and animals. The rise of antimicrobial resistance and the inefficacy of existing vaccines highlight the urgent need for new preventive strategies.MethodsAn immunoinformatics approach was employed to design a multi-epitope subunit vaccine (MESV) against leptospirosis. B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes were selected from five key Leptospira proteins. These epitopes were fused with a heparin-binding hemagglutinin (HBHA) adjuvant and appropriate linkers to construct the broad-spectrum vaccine. The physicochemical properties of the vaccine were assessed, including antigenicity, immunogenicity, allergenicity, and conservation. The vaccine’s 3D structure was modeled, optimized, and validated. Molecular docking, molecular dynamics simulations, and MM-GBSA analysis were performed to assess the vaccine's binding interactions with Toll-like receptors (TLR2 and TLR4). Immune simulations and in silico cloning were also conducted to evaluate the vaccine’s immune response and expression potential.ResultsThe MESV demonstrated high antigenicity, immunogenicity, non-allergenicity, and conservation across different Leptospira strains. Population coverage analysis revealed that T-cell epitopes significantly interacted with HLA molecules, covering 95.7% of the global population. Molecular docking showed strong and stable binding with TLR2 and TLR4, with binding energies of -1,357.1 kJ/mol and -1,163.7 kJ/mol, respectively. Molecular dynamics simulations and MM-GBSA analysis confirmed the stability of these interactions and accurately calculated the intermolecular binding free energies. Immune simulations indicated robust B and T cell responses, and in silico cloning demonstrated that the vaccine could be successfully expressed in E. coli.DiscussionThese findings suggest that MESV is a promising candidate for leptospirosis prevention, providing robust immune responses and broad population coverage. However, further in vivo studies are necessary to validate its efficacy and safety. |
| format | Article |
| id | doaj-art-741c8c7f18a24afba1dd6dd9192b1eef |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-741c8c7f18a24afba1dd6dd9192b1eef2025-01-28T06:41:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15038531503853Designing a broad-spectrum multi-epitope subunit vaccine against leptospirosis using immunoinformatics and structural approachesGuneswar Sethi0Guneswar Sethi1Young Kyu Kim2Su-Cheol Han3Jeong Ho Hwang4Jeong Ho Hwang5Animal Model Research Group, Korea Institute of Toxicology, Jeonguep, Jeollabuk-do, Republic of KoreaCenter for Companion Animal New Drug Development, Korea Institute of Toxicology, Jeonguep, Jeollabuk-do, Republic of KoreaAnimal Model Research Group, Korea Institute of Toxicology, Jeonguep, Jeollabuk-do, Republic of KoreaCenter for Companion Animal New Drug Development, Korea Institute of Toxicology, Jeonguep, Jeollabuk-do, Republic of KoreaAnimal Model Research Group, Korea Institute of Toxicology, Jeonguep, Jeollabuk-do, Republic of KoreaCenter for Companion Animal New Drug Development, Korea Institute of Toxicology, Jeonguep, Jeollabuk-do, Republic of KoreaIntroductionLeptospirosis, caused by Leptospira interrogans, is a neglected zoonotic disease that poses a significant global health risk to both humans and animals. The rise of antimicrobial resistance and the inefficacy of existing vaccines highlight the urgent need for new preventive strategies.MethodsAn immunoinformatics approach was employed to design a multi-epitope subunit vaccine (MESV) against leptospirosis. B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes were selected from five key Leptospira proteins. These epitopes were fused with a heparin-binding hemagglutinin (HBHA) adjuvant and appropriate linkers to construct the broad-spectrum vaccine. The physicochemical properties of the vaccine were assessed, including antigenicity, immunogenicity, allergenicity, and conservation. The vaccine’s 3D structure was modeled, optimized, and validated. Molecular docking, molecular dynamics simulations, and MM-GBSA analysis were performed to assess the vaccine's binding interactions with Toll-like receptors (TLR2 and TLR4). Immune simulations and in silico cloning were also conducted to evaluate the vaccine’s immune response and expression potential.ResultsThe MESV demonstrated high antigenicity, immunogenicity, non-allergenicity, and conservation across different Leptospira strains. Population coverage analysis revealed that T-cell epitopes significantly interacted with HLA molecules, covering 95.7% of the global population. Molecular docking showed strong and stable binding with TLR2 and TLR4, with binding energies of -1,357.1 kJ/mol and -1,163.7 kJ/mol, respectively. Molecular dynamics simulations and MM-GBSA analysis confirmed the stability of these interactions and accurately calculated the intermolecular binding free energies. Immune simulations indicated robust B and T cell responses, and in silico cloning demonstrated that the vaccine could be successfully expressed in E. coli.DiscussionThese findings suggest that MESV is a promising candidate for leptospirosis prevention, providing robust immune responses and broad population coverage. However, further in vivo studies are necessary to validate its efficacy and safety.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1503853/fullleptospirosismulti-epitope subunit vaccineimmunoinformaticspopulation coveragemolecular dockingmolecular dynamics simulation |
| spellingShingle | Guneswar Sethi Guneswar Sethi Young Kyu Kim Su-Cheol Han Jeong Ho Hwang Jeong Ho Hwang Designing a broad-spectrum multi-epitope subunit vaccine against leptospirosis using immunoinformatics and structural approaches Frontiers in Immunology leptospirosis multi-epitope subunit vaccine immunoinformatics population coverage molecular docking molecular dynamics simulation |
| title | Designing a broad-spectrum multi-epitope subunit vaccine against leptospirosis using immunoinformatics and structural approaches |
| title_full | Designing a broad-spectrum multi-epitope subunit vaccine against leptospirosis using immunoinformatics and structural approaches |
| title_fullStr | Designing a broad-spectrum multi-epitope subunit vaccine against leptospirosis using immunoinformatics and structural approaches |
| title_full_unstemmed | Designing a broad-spectrum multi-epitope subunit vaccine against leptospirosis using immunoinformatics and structural approaches |
| title_short | Designing a broad-spectrum multi-epitope subunit vaccine against leptospirosis using immunoinformatics and structural approaches |
| title_sort | designing a broad spectrum multi epitope subunit vaccine against leptospirosis using immunoinformatics and structural approaches |
| topic | leptospirosis multi-epitope subunit vaccine immunoinformatics population coverage molecular docking molecular dynamics simulation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1503853/full |
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