Engineering Modified mRNA-Based Vaccine against Dengue Virus Using Computational and Reverse Vaccinology Approaches
Dengue virus belonging to the family <i>Flaviviridae</i> and its four serotypes are responsible for dengue infections, which extend over 60 countries in tropical and subtropical areas of the world including Pakistan. During the ongoing dengue outbreak in Pakistan (2022), over 30,000 case...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/13911 |
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| author | Mamuna Mukhtar Amtul Wadood Wajeeha Najam us Sahar Sadaf Zaidi Naseeha Bibi |
| author_facet | Mamuna Mukhtar Amtul Wadood Wajeeha Najam us Sahar Sadaf Zaidi Naseeha Bibi |
| author_sort | Mamuna Mukhtar |
| collection | DOAJ |
| description | Dengue virus belonging to the family <i>Flaviviridae</i> and its four serotypes are responsible for dengue infections, which extend over 60 countries in tropical and subtropical areas of the world including Pakistan. During the ongoing dengue outbreak in Pakistan (2022), over 30,000 cases have been reported, and over 70 lives have been lost. The only commercialized vaccine against DENV, Dengvaxia, cannot be administered as a prophylactic measure to cure this infection due to various complications. Using machine learning and reverse vaccinology approaches, this study was designed to develop a tetravalent modified nucleotide mRNA vaccine using NS1, prM, and EIII sequences of dengue virus from Pakistani isolates. Based on high antigenicity, non-allergenicity, and toxicity profiling, B-cell epitope, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) putative vaccine targets were predicted. Molecular docking confirmed favorable interactions between T-cell epitopes and their respective HLA alleles, while normal mode analysis validated high-affinity interactions of vaccine proteins with immune receptors. In silico immune simulations confirmed adequate immune responses to eliminate the antigen and generate memory. Codon optimization, physicochemical features, nucleotide modifications, and suitable vector availability further ensured better antigen expression and adaptive immune responses. We predict that this vaccine construct may prove to be a good vaccinal candidate against dengue virus in vitro as well. |
| first_indexed | 2024-03-09T18:17:24Z |
| format | Article |
| id | doaj.art-1cde77e1bee24afdb6ef703833389607 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:17:24Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1cde77e1bee24afdb6ef7038333896072023-11-24T08:35:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221391110.3390/ijms232213911Engineering Modified mRNA-Based Vaccine against Dengue Virus Using Computational and Reverse Vaccinology ApproachesMamuna Mukhtar0Amtul Wadood Wajeeha1Najam us Sahar Sadaf Zaidi2Naseeha Bibi3Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad 44000, PakistanAtta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad 44000, PakistanAtta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad 44000, PakistanAtta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad 44000, PakistanDengue virus belonging to the family <i>Flaviviridae</i> and its four serotypes are responsible for dengue infections, which extend over 60 countries in tropical and subtropical areas of the world including Pakistan. During the ongoing dengue outbreak in Pakistan (2022), over 30,000 cases have been reported, and over 70 lives have been lost. The only commercialized vaccine against DENV, Dengvaxia, cannot be administered as a prophylactic measure to cure this infection due to various complications. Using machine learning and reverse vaccinology approaches, this study was designed to develop a tetravalent modified nucleotide mRNA vaccine using NS1, prM, and EIII sequences of dengue virus from Pakistani isolates. Based on high antigenicity, non-allergenicity, and toxicity profiling, B-cell epitope, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) putative vaccine targets were predicted. Molecular docking confirmed favorable interactions between T-cell epitopes and their respective HLA alleles, while normal mode analysis validated high-affinity interactions of vaccine proteins with immune receptors. In silico immune simulations confirmed adequate immune responses to eliminate the antigen and generate memory. Codon optimization, physicochemical features, nucleotide modifications, and suitable vector availability further ensured better antigen expression and adaptive immune responses. We predict that this vaccine construct may prove to be a good vaccinal candidate against dengue virus in vitro as well.https://www.mdpi.com/1422-0067/23/22/13911dengue virusmRNA vaccinesreverse vaccinologymolecular dockingnormal mode analysisimmune simulations |
| spellingShingle | Mamuna Mukhtar Amtul Wadood Wajeeha Najam us Sahar Sadaf Zaidi Naseeha Bibi Engineering Modified mRNA-Based Vaccine against Dengue Virus Using Computational and Reverse Vaccinology Approaches International Journal of Molecular Sciences dengue virus mRNA vaccines reverse vaccinology molecular docking normal mode analysis immune simulations |
| title | Engineering Modified mRNA-Based Vaccine against Dengue Virus Using Computational and Reverse Vaccinology Approaches |
| title_full | Engineering Modified mRNA-Based Vaccine against Dengue Virus Using Computational and Reverse Vaccinology Approaches |
| title_fullStr | Engineering Modified mRNA-Based Vaccine against Dengue Virus Using Computational and Reverse Vaccinology Approaches |
| title_full_unstemmed | Engineering Modified mRNA-Based Vaccine against Dengue Virus Using Computational and Reverse Vaccinology Approaches |
| title_short | Engineering Modified mRNA-Based Vaccine against Dengue Virus Using Computational and Reverse Vaccinology Approaches |
| title_sort | engineering modified mrna based vaccine against dengue virus using computational and reverse vaccinology approaches |
| topic | dengue virus mRNA vaccines reverse vaccinology molecular docking normal mode analysis immune simulations |
| url | https://www.mdpi.com/1422-0067/23/22/13911 |
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