In Silico Design of a Trans-Amplifying RNA-Based Vaccine against SARS-CoV-2 Structural Proteins
Nucleic acid-based vaccines allow scalable, rapid, and cell-free vaccine production in response to an emerging disease such as the current COVID-19 pandemic. Here, we objected to the design of a multiepitope mRNA vaccine against the structural proteins of SARS-CoV-2. Through an immunoinformatic appr...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Advances in Virology |
| Online Access: | http://dx.doi.org/10.1155/2024/3418062 |
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| author | Fatemeh Nafian Ghazal Soleymani Zahra Pourmanouchehri Mahnaz Kiyanjam Simin Nafian Sayed Mohammad Mohammadi Hanie Jeyroudi Sharareh Berenji Jalaei Fatemeh Sabzpoushan |
| author_facet | Fatemeh Nafian Ghazal Soleymani Zahra Pourmanouchehri Mahnaz Kiyanjam Simin Nafian Sayed Mohammad Mohammadi Hanie Jeyroudi Sharareh Berenji Jalaei Fatemeh Sabzpoushan |
| author_sort | Fatemeh Nafian |
| collection | DOAJ |
| description | Nucleic acid-based vaccines allow scalable, rapid, and cell-free vaccine production in response to an emerging disease such as the current COVID-19 pandemic. Here, we objected to the design of a multiepitope mRNA vaccine against the structural proteins of SARS-CoV-2. Through an immunoinformatic approach, promising epitopes were predicted for the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. Fragments rich in overlapping epitopes were selected based on binding affinities with HLA classes I and II for the specific presentation to B and T lymphocytes. Two constructs were designed by fusing the fragments in different arrangements via GG linkers. Construct 1 showed better structural properties and interactions with toll-like receptor 2 (TLR-2), TLR-3, and TLR-4 during molecular docking and dynamic simulation. A 50S ribosomal L7/L12 adjuvant was added to its N-terminus to improve stability and immunogenicity. The final RNA sequence was used to design a trans-amplifying RNA (taRNA) vaccine in a split-vector system. It consists of two molecules: a nonreplicating RNA encoding a trans-acting replicase to amplify the second one, a trans-replicon (TR) RNA encoding the vaccine protein. Overall, the immune response simulation detected that activated B and T lymphocytes and increased memory cell formation. Macrophages and dendritic cells proliferated continuously, and IFN-γ and cytokines like IL-2 were released highly. |
| format | Article |
| id | doaj-art-c899dc8238614d6c8abd3a4a92fb196b |
| institution | Kabale University |
| issn | 1687-8647 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advances in Virology |
| spelling | doaj-art-c899dc8238614d6c8abd3a4a92fb196b2025-02-02T23:07:29ZengWileyAdvances in Virology1687-86472024-01-01202410.1155/2024/3418062In Silico Design of a Trans-Amplifying RNA-Based Vaccine against SARS-CoV-2 Structural ProteinsFatemeh Nafian0Ghazal Soleymani1Zahra Pourmanouchehri2Mahnaz Kiyanjam3Simin Nafian4Sayed Mohammad Mohammadi5Hanie Jeyroudi6Sharareh Berenji Jalaei7Fatemeh Sabzpoushan8Department of Medical Laboratory SciencesDepartment of Biological SciencesDepartment of BiologyDepartment of Cellular and Molecular BiologyDepartment of Stem Cell and Regenerative MedicineDepartment of BiotechnologyDepartment of Cellular and Molecular BiologyDepartment of BiochemistryDepartment of Cellular and Molecular BiologyNucleic acid-based vaccines allow scalable, rapid, and cell-free vaccine production in response to an emerging disease such as the current COVID-19 pandemic. Here, we objected to the design of a multiepitope mRNA vaccine against the structural proteins of SARS-CoV-2. Through an immunoinformatic approach, promising epitopes were predicted for the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. Fragments rich in overlapping epitopes were selected based on binding affinities with HLA classes I and II for the specific presentation to B and T lymphocytes. Two constructs were designed by fusing the fragments in different arrangements via GG linkers. Construct 1 showed better structural properties and interactions with toll-like receptor 2 (TLR-2), TLR-3, and TLR-4 during molecular docking and dynamic simulation. A 50S ribosomal L7/L12 adjuvant was added to its N-terminus to improve stability and immunogenicity. The final RNA sequence was used to design a trans-amplifying RNA (taRNA) vaccine in a split-vector system. It consists of two molecules: a nonreplicating RNA encoding a trans-acting replicase to amplify the second one, a trans-replicon (TR) RNA encoding the vaccine protein. Overall, the immune response simulation detected that activated B and T lymphocytes and increased memory cell formation. Macrophages and dendritic cells proliferated continuously, and IFN-γ and cytokines like IL-2 were released highly.http://dx.doi.org/10.1155/2024/3418062 |
| spellingShingle | Fatemeh Nafian Ghazal Soleymani Zahra Pourmanouchehri Mahnaz Kiyanjam Simin Nafian Sayed Mohammad Mohammadi Hanie Jeyroudi Sharareh Berenji Jalaei Fatemeh Sabzpoushan In Silico Design of a Trans-Amplifying RNA-Based Vaccine against SARS-CoV-2 Structural Proteins Advances in Virology |
| title | In Silico Design of a Trans-Amplifying RNA-Based Vaccine against SARS-CoV-2 Structural Proteins |
| title_full | In Silico Design of a Trans-Amplifying RNA-Based Vaccine against SARS-CoV-2 Structural Proteins |
| title_fullStr | In Silico Design of a Trans-Amplifying RNA-Based Vaccine against SARS-CoV-2 Structural Proteins |
| title_full_unstemmed | In Silico Design of a Trans-Amplifying RNA-Based Vaccine against SARS-CoV-2 Structural Proteins |
| title_short | In Silico Design of a Trans-Amplifying RNA-Based Vaccine against SARS-CoV-2 Structural Proteins |
| title_sort | in silico design of a trans amplifying rna based vaccine against sars cov 2 structural proteins |
| url | http://dx.doi.org/10.1155/2024/3418062 |
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