Immunoinformatics Approach to Design a Chimeric CD70-Peptide Vaccine against Renal Cell Carcinoma
Renal cell carcinoma (RCC) accounts for the majority of cancer-related deaths worldwide. Overexpression of CD70 has been linked to advanced stages of RCC. Therefore, this study aims to develop a multiepitope vaccine targeting the overexpressed CD70 using immunoinformatics techniques. In this investi...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2024/2875635 |
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| author | Haideh Namdari Farhad Rezaei Fatemeh Heidarnejad Mohammad Yaghoubzad-Maleki Maryam Karamigolbaghi |
| author_facet | Haideh Namdari Farhad Rezaei Fatemeh Heidarnejad Mohammad Yaghoubzad-Maleki Maryam Karamigolbaghi |
| author_sort | Haideh Namdari |
| collection | DOAJ |
| description | Renal cell carcinoma (RCC) accounts for the majority of cancer-related deaths worldwide. Overexpression of CD70 has been linked to advanced stages of RCC. Therefore, this study aims to develop a multiepitope vaccine targeting the overexpressed CD70 using immunoinformatics techniques. In this investigation, in silico multiepitope vaccines were constructed by linking specific CD70 protein epitopes for helper T lymphocytes and CD8+ T lymphocytes. To enhance immunogenicity, sequences of cell-penetrating peptide (CPP), penetratin (pAntp), along with the entire sequence of tumor necrosis factor-α (TNF-α), were attached to the N-terminal and C-terminal of the CD70 epitopes. Computational assessments were performed on these chimeric vaccines for antigenicity, allergenicity, peptide toxicity, population coverage, and physicochemical properties. Furthermore, refined 3D constructs were subjected to a range of analyses, encompassing structural B-cell epitope prediction and molecular docking. The chosen vaccine construct underwent diverse assessments such as molecular dynamics simulation, immune response simulation, and in silico cloning. All vaccines comprised antigenic, nontoxic, and nonallergenic epitopes, ensuring extensive global population coverage. The vaccine constructs demonstrated favorable physicochemical characteristics. The binding affinity of chimeric vaccines to the TNF receptor remained relatively stable, influenced by the alignment of vaccine components. Molecular docking and dynamics analyses predicted stable interactions between CD70-CPP-TNF and the TNF receptor, indicating potential efficacy. In silico codon optimization and cloning of the vaccine nucleic acid sequence were accomplished using the pET28a plasmid. Furthermore, this vaccine displayed the capacity to modulate humoral and cellular immune responses. Overall, the results suggest therapeutic potential for the chimeric CD70-CPP-TNF vaccine against RCC. However, validation through in vitro and in vivo experiments is necessary. This trial is registered with NCT04696731 and NCT04046445. |
| format | Article |
| id | doaj-art-64c7e1899c8f4fff809adc2b06ca7b98 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-64c7e1899c8f4fff809adc2b06ca7b982025-02-03T01:29:49ZengWileyJournal of Immunology Research2314-71562024-01-01202410.1155/2024/2875635Immunoinformatics Approach to Design a Chimeric CD70-Peptide Vaccine against Renal Cell CarcinomaHaideh Namdari0Farhad Rezaei1Fatemeh Heidarnejad2Mohammad Yaghoubzad-Maleki3Maryam Karamigolbaghi4Iranian Tissue Bank and Research CenterVirology DepartmentBiotechnology Research Center (BRC)Division of BiochemistryIranian Tissue Bank and Research CenterRenal cell carcinoma (RCC) accounts for the majority of cancer-related deaths worldwide. Overexpression of CD70 has been linked to advanced stages of RCC. Therefore, this study aims to develop a multiepitope vaccine targeting the overexpressed CD70 using immunoinformatics techniques. In this investigation, in silico multiepitope vaccines were constructed by linking specific CD70 protein epitopes for helper T lymphocytes and CD8+ T lymphocytes. To enhance immunogenicity, sequences of cell-penetrating peptide (CPP), penetratin (pAntp), along with the entire sequence of tumor necrosis factor-α (TNF-α), were attached to the N-terminal and C-terminal of the CD70 epitopes. Computational assessments were performed on these chimeric vaccines for antigenicity, allergenicity, peptide toxicity, population coverage, and physicochemical properties. Furthermore, refined 3D constructs were subjected to a range of analyses, encompassing structural B-cell epitope prediction and molecular docking. The chosen vaccine construct underwent diverse assessments such as molecular dynamics simulation, immune response simulation, and in silico cloning. All vaccines comprised antigenic, nontoxic, and nonallergenic epitopes, ensuring extensive global population coverage. The vaccine constructs demonstrated favorable physicochemical characteristics. The binding affinity of chimeric vaccines to the TNF receptor remained relatively stable, influenced by the alignment of vaccine components. Molecular docking and dynamics analyses predicted stable interactions between CD70-CPP-TNF and the TNF receptor, indicating potential efficacy. In silico codon optimization and cloning of the vaccine nucleic acid sequence were accomplished using the pET28a plasmid. Furthermore, this vaccine displayed the capacity to modulate humoral and cellular immune responses. Overall, the results suggest therapeutic potential for the chimeric CD70-CPP-TNF vaccine against RCC. However, validation through in vitro and in vivo experiments is necessary. This trial is registered with NCT04696731 and NCT04046445.http://dx.doi.org/10.1155/2024/2875635 |
| spellingShingle | Haideh Namdari Farhad Rezaei Fatemeh Heidarnejad Mohammad Yaghoubzad-Maleki Maryam Karamigolbaghi Immunoinformatics Approach to Design a Chimeric CD70-Peptide Vaccine against Renal Cell Carcinoma Journal of Immunology Research |
| title | Immunoinformatics Approach to Design a Chimeric CD70-Peptide Vaccine against Renal Cell Carcinoma |
| title_full | Immunoinformatics Approach to Design a Chimeric CD70-Peptide Vaccine against Renal Cell Carcinoma |
| title_fullStr | Immunoinformatics Approach to Design a Chimeric CD70-Peptide Vaccine against Renal Cell Carcinoma |
| title_full_unstemmed | Immunoinformatics Approach to Design a Chimeric CD70-Peptide Vaccine against Renal Cell Carcinoma |
| title_short | Immunoinformatics Approach to Design a Chimeric CD70-Peptide Vaccine against Renal Cell Carcinoma |
| title_sort | immunoinformatics approach to design a chimeric cd70 peptide vaccine against renal cell carcinoma |
| url | http://dx.doi.org/10.1155/2024/2875635 |
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