Immunoinformatic approach to the design of a novel multi-epitope vaccine against Leishmania major fused to human IgG-Fc
Background and purpose: Cutaneous leishmaniasis poses significant health and socioeconomic challenges, making vaccine development a top priority, especially in endemic regions. Cysteine proteases, KMP-11, and HASPB proteins are promising candidates for leishmaniasis vaccine development owing to thei...
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2024-12-01
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| Series: | Research in Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | https://journals.lww.com/10.4103/RPS.RPS_145_24 |
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| author | Mahmood Fadaie Zabihollah Shahmoradi Hossein Khanahmad |
| author_facet | Mahmood Fadaie Zabihollah Shahmoradi Hossein Khanahmad |
| author_sort | Mahmood Fadaie |
| collection | DOAJ |
| description | Background and purpose:
Cutaneous leishmaniasis poses significant health and socioeconomic challenges, making vaccine development a top priority, especially in endemic regions. Cysteine proteases, KMP-11, and HASPB proteins are promising candidates for leishmaniasis vaccine development owing to their immunogenic properties and capacity to provoke robust immune responses, as evidenced by different investigations. This study aimed to design a recombinant chimeric protein (MEV-Fc) vaccine using multi-epitopes from these Leishmania major proteins.
Experimental approach:
The antigens were subjected to immunoinformatic prediction and screening of HTL, CTL, and B-cell epitopes. The multi-epitope protein was designed with significantly high-scoring epitopes and suitable linkers. Natural adjuvants were then added to enhance immunogenicity. Vaccine potency was innovatively improved by covalently fusing human IgG1 Fc with multi-epitope protein. To investigate how the MEV-Fc vaccine interacts with Toll-like receptors, molecular docking, multi-scale normal mode analysis simulation, and computational immune simulation were employed to study humoral and cellular immune responses.
Findings/Results:
The results demonstrated the vaccine’s antigenicity, stability, and nontoxicity. The structural validation confirmed the accuracy of the 3D models, indicating robust interactions with TLR2 and TLR4, with binding free energies of -1269.9 and -1128.7 (kcal/mol), respectively. Immune simulation results showed significant increases in IgM and IgG antibody levels following three vaccinations, along with enhanced activation of B cells, helper T cells, and cytotoxic T lymphocytes.
Conclusion and implications:
These findings provide novel insights for developing effective candidates for cutaneous leishmaniasis vaccines. However, laboratory experiments are necessary to evaluate its protective effects. |
| format | Article |
| id | doaj-art-18e2287c24fe4e458737c402cab0ecc2 |
| institution | Kabale University |
| issn | 1735-5362 1735-9414 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Research in Pharmaceutical Sciences |
| spelling | doaj-art-18e2287c24fe4e458737c402cab0ecc22025-01-07T09:56:57ZengWolters Kluwer Medknow PublicationsResearch in Pharmaceutical Sciences1735-53621735-94142024-12-0119672974510.4103/RPS.RPS_145_24Immunoinformatic approach to the design of a novel multi-epitope vaccine against Leishmania major fused to human IgG-FcMahmood FadaieZabihollah ShahmoradiHossein KhanahmadBackground and purpose: Cutaneous leishmaniasis poses significant health and socioeconomic challenges, making vaccine development a top priority, especially in endemic regions. Cysteine proteases, KMP-11, and HASPB proteins are promising candidates for leishmaniasis vaccine development owing to their immunogenic properties and capacity to provoke robust immune responses, as evidenced by different investigations. This study aimed to design a recombinant chimeric protein (MEV-Fc) vaccine using multi-epitopes from these Leishmania major proteins. Experimental approach: The antigens were subjected to immunoinformatic prediction and screening of HTL, CTL, and B-cell epitopes. The multi-epitope protein was designed with significantly high-scoring epitopes and suitable linkers. Natural adjuvants were then added to enhance immunogenicity. Vaccine potency was innovatively improved by covalently fusing human IgG1 Fc with multi-epitope protein. To investigate how the MEV-Fc vaccine interacts with Toll-like receptors, molecular docking, multi-scale normal mode analysis simulation, and computational immune simulation were employed to study humoral and cellular immune responses. Findings/Results: The results demonstrated the vaccine’s antigenicity, stability, and nontoxicity. The structural validation confirmed the accuracy of the 3D models, indicating robust interactions with TLR2 and TLR4, with binding free energies of -1269.9 and -1128.7 (kcal/mol), respectively. Immune simulation results showed significant increases in IgM and IgG antibody levels following three vaccinations, along with enhanced activation of B cells, helper T cells, and cytotoxic T lymphocytes. Conclusion and implications: These findings provide novel insights for developing effective candidates for cutaneous leishmaniasis vaccines. However, laboratory experiments are necessary to evaluate its protective effects.https://journals.lww.com/10.4103/RPS.RPS_145_24adjuvantigg-fcimmunodominant epitopesleishmania majorsubunit vaccine |
| spellingShingle | Mahmood Fadaie Zabihollah Shahmoradi Hossein Khanahmad Immunoinformatic approach to the design of a novel multi-epitope vaccine against Leishmania major fused to human IgG-Fc Research in Pharmaceutical Sciences adjuvant igg-fc immunodominant epitopes leishmania major subunit vaccine |
| title | Immunoinformatic approach to the design of a novel multi-epitope vaccine against Leishmania major fused to human IgG-Fc |
| title_full | Immunoinformatic approach to the design of a novel multi-epitope vaccine against Leishmania major fused to human IgG-Fc |
| title_fullStr | Immunoinformatic approach to the design of a novel multi-epitope vaccine against Leishmania major fused to human IgG-Fc |
| title_full_unstemmed | Immunoinformatic approach to the design of a novel multi-epitope vaccine against Leishmania major fused to human IgG-Fc |
| title_short | Immunoinformatic approach to the design of a novel multi-epitope vaccine against Leishmania major fused to human IgG-Fc |
| title_sort | immunoinformatic approach to the design of a novel multi epitope vaccine against leishmania major fused to human igg fc |
| topic | adjuvant igg-fc immunodominant epitopes leishmania major subunit vaccine |
| url | https://journals.lww.com/10.4103/RPS.RPS_145_24 |
| work_keys_str_mv | AT mahmoodfadaie immunoinformaticapproachtothedesignofanovelmultiepitopevaccineagainstleishmaniamajorfusedtohumaniggfc AT zabihollahshahmoradi immunoinformaticapproachtothedesignofanovelmultiepitopevaccineagainstleishmaniamajorfusedtohumaniggfc AT hosseinkhanahmad immunoinformaticapproachtothedesignofanovelmultiepitopevaccineagainstleishmaniamajorfusedtohumaniggfc |