Design of a Multi-Epitopes Vaccine against Hantaviruses: An Immunoinformatics and Molecular Modelling Approach
Hantaviruses are negative-sense, enveloped, single-stranded RNA viruses of the family Hantaviridae. In recent years, rodent-borne hantaviruses have emerged as novel zoonotic viruses posing a substantial health issue and socioeconomic burden. In the current research, a reverse vaccinology approach wa...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/3/378 |
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| author | Saba Ismail Sumra Wajid Abbasi Maha Yousaf Sajjad Ahmad Khalid Muhammad Yasir Waheed |
| author_facet | Saba Ismail Sumra Wajid Abbasi Maha Yousaf Sajjad Ahmad Khalid Muhammad Yasir Waheed |
| author_sort | Saba Ismail |
| collection | DOAJ |
| description | Hantaviruses are negative-sense, enveloped, single-stranded RNA viruses of the family Hantaviridae. In recent years, rodent-borne hantaviruses have emerged as novel zoonotic viruses posing a substantial health issue and socioeconomic burden. In the current research, a reverse vaccinology approach was applied to design a multi-epitope-based vaccine against hantavirus. A set of 340 experimentally reported epitopes were retrieved from Virus Pathogen Database and Analysis Resource (ViPR) and subjected to different analyses such as antigenicity, allergenicity, solubility, IFN gamma, toxicity, and virulent checks. Finally, 10 epitopes which cleared all the filters used were linked with each other through specific GPGPG linkers to construct a multi-antigenic epitope vaccine. The designed vaccine was then joined to three different adjuvants—TLR4-agonist adjuvant, β-defensin, and 50S ribosomal protein L7/L12—using an EAAAK linker to boost up immune-stimulating responses and check the potency of vaccine with each adjuvant. The designed vaccine structures were modelled and subjected to error refinement and disulphide engineering to enhance their stability. To understand the vaccine binding affinity with immune cell receptors, molecular docking was performed between the designed vaccines and TLR4; the docked complex with a low level of global energy was then subjected to molecular dynamics simulations to validate the docking results and dynamic behaviour. The docking binding energy of vaccines with TLR4 is −29.63 kcal/mol (TLR4-agonist), −3.41 kcal/mol (β-defensin), and −11.03 kcal/mol (50S ribosomal protein L7/L12). The systems dynamics revealed all three systems to be highly stable with a root-mean-square deviation (RMSD) value within 3 Å. To test docking predictions and determine dominant interaction energies, binding free energies of vaccine(s)–TLR4 complexes were calculated. The net binding energy of the systems was as follows: TLR4-agonist vaccine with TLR4 (MM–GBSA, −1628.47 kcal/mol and MM–PBSA, −37.75 kcal/mol); 50S ribosomal protein L7/L12 vaccine with TLR4 complex (MM–GBSA, −194.62 kcal/mol and MM–PBSA, −150.67 kcal/mol); β-defensin vaccine with TLR4 complex (MM–GBSA, −9.80 kcal/mol and MM–PBSA, −42.34 kcal/mol). Finally, these findings may aid experimental vaccinologists in developing a very potent hantavirus vaccine. |
| first_indexed | 2024-03-09T12:20:07Z |
| format | Article |
| id | doaj.art-b6875f12e30244ea99ea8db60bf5ff69 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T12:20:07Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-b6875f12e30244ea99ea8db60bf5ff692023-11-30T22:42:07ZengMDPI AGVaccines2076-393X2022-02-0110337810.3390/vaccines10030378Design of a Multi-Epitopes Vaccine against Hantaviruses: An Immunoinformatics and Molecular Modelling ApproachSaba Ismail0Sumra Wajid Abbasi1Maha Yousaf2Sajjad Ahmad3Khalid Muhammad4Yasir Waheed5Foundation University Medical College, Foundation University Islamabad, Islamabad 44000, PakistanNUMS Department of Biological Sciences, National University of Medical Sciences, Abid Majeed Rd, The Mall, Rawalpindi 46000, PakistanDepartment of Biosciences, COMSATS University Islamabad, Islamabad 45550, PakistanDepartment of Health and Biological Sciences, Abasyn University, Peshawar 25000, PakistanDepartment of Biology, College of Science, United Arab Emirates University, Al Ain 15551, United Arab EmiratesFoundation University Medical College, Foundation University Islamabad, Islamabad 44000, PakistanHantaviruses are negative-sense, enveloped, single-stranded RNA viruses of the family Hantaviridae. In recent years, rodent-borne hantaviruses have emerged as novel zoonotic viruses posing a substantial health issue and socioeconomic burden. In the current research, a reverse vaccinology approach was applied to design a multi-epitope-based vaccine against hantavirus. A set of 340 experimentally reported epitopes were retrieved from Virus Pathogen Database and Analysis Resource (ViPR) and subjected to different analyses such as antigenicity, allergenicity, solubility, IFN gamma, toxicity, and virulent checks. Finally, 10 epitopes which cleared all the filters used were linked with each other through specific GPGPG linkers to construct a multi-antigenic epitope vaccine. The designed vaccine was then joined to three different adjuvants—TLR4-agonist adjuvant, β-defensin, and 50S ribosomal protein L7/L12—using an EAAAK linker to boost up immune-stimulating responses and check the potency of vaccine with each adjuvant. The designed vaccine structures were modelled and subjected to error refinement and disulphide engineering to enhance their stability. To understand the vaccine binding affinity with immune cell receptors, molecular docking was performed between the designed vaccines and TLR4; the docked complex with a low level of global energy was then subjected to molecular dynamics simulations to validate the docking results and dynamic behaviour. The docking binding energy of vaccines with TLR4 is −29.63 kcal/mol (TLR4-agonist), −3.41 kcal/mol (β-defensin), and −11.03 kcal/mol (50S ribosomal protein L7/L12). The systems dynamics revealed all three systems to be highly stable with a root-mean-square deviation (RMSD) value within 3 Å. To test docking predictions and determine dominant interaction energies, binding free energies of vaccine(s)–TLR4 complexes were calculated. The net binding energy of the systems was as follows: TLR4-agonist vaccine with TLR4 (MM–GBSA, −1628.47 kcal/mol and MM–PBSA, −37.75 kcal/mol); 50S ribosomal protein L7/L12 vaccine with TLR4 complex (MM–GBSA, −194.62 kcal/mol and MM–PBSA, −150.67 kcal/mol); β-defensin vaccine with TLR4 complex (MM–GBSA, −9.80 kcal/mol and MM–PBSA, −42.34 kcal/mol). Finally, these findings may aid experimental vaccinologists in developing a very potent hantavirus vaccine.https://www.mdpi.com/2076-393X/10/3/378hantavirusesViPR databasemulti-epitope databasemolecular dynamics simulationsbinding free energies |
| spellingShingle | Saba Ismail Sumra Wajid Abbasi Maha Yousaf Sajjad Ahmad Khalid Muhammad Yasir Waheed Design of a Multi-Epitopes Vaccine against Hantaviruses: An Immunoinformatics and Molecular Modelling Approach Vaccines hantaviruses ViPR database multi-epitope database molecular dynamics simulations binding free energies |
| title | Design of a Multi-Epitopes Vaccine against Hantaviruses: An Immunoinformatics and Molecular Modelling Approach |
| title_full | Design of a Multi-Epitopes Vaccine against Hantaviruses: An Immunoinformatics and Molecular Modelling Approach |
| title_fullStr | Design of a Multi-Epitopes Vaccine against Hantaviruses: An Immunoinformatics and Molecular Modelling Approach |
| title_full_unstemmed | Design of a Multi-Epitopes Vaccine against Hantaviruses: An Immunoinformatics and Molecular Modelling Approach |
| title_short | Design of a Multi-Epitopes Vaccine against Hantaviruses: An Immunoinformatics and Molecular Modelling Approach |
| title_sort | design of a multi epitopes vaccine against hantaviruses an immunoinformatics and molecular modelling approach |
| topic | hantaviruses ViPR database multi-epitope database molecular dynamics simulations binding free energies |
| url | https://www.mdpi.com/2076-393X/10/3/378 |
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