Cytotoxic T-Cell-Based Vaccine against SARS-CoV-2: A Hybrid Immunoinformatic Approach
This paper presents an alternative vaccination platform that provides long-term cellular immune protection mediated by cytotoxic T-cells. The immune response via cellular immunity creates superior resistance to viral mutations, which are currently the greatest threat to the global vaccination campai...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/2/218 |
| _version_ | 1797476152812503040 |
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| author | Alexandru Tirziu Virgil Paunescu |
| author_facet | Alexandru Tirziu Virgil Paunescu |
| author_sort | Alexandru Tirziu |
| collection | DOAJ |
| description | This paper presents an alternative vaccination platform that provides long-term cellular immune protection mediated by cytotoxic T-cells. The immune response via cellular immunity creates superior resistance to viral mutations, which are currently the greatest threat to the global vaccination campaign. Furthermore, we also propose a safer, more facile, and physiologically appropriate immunization method using either intranasal or oral administration. The underlying technology is an adaptation of synthetic long peptides (SLPs) previously used in cancer immunotherapy. The overall quality of the SLP constructs was validated using in silico methods. SLPs comprising HLA class I and class II epitopes were designed to stimulate antigen cross-presentation and canonical class II presentation by dendritic cells. The desired effect is a cytotoxic T cell-mediated prompt and specific immune response against the virus-infected epithelia and a rapid and robust virus clearance. Epitopes isolated from COVID-19 convalescent patients were screened for HLA class I and class II binding (NetMHCpan and NetMHCIIpan) and highest HLA population coverage (IEDB Population Coverage). 15 class I and 4 class II epitopes were identified and used for this SLP design. The constructs were characterized based on their toxicity (ToxinPred), allergenicity (AllerCatPro), immunogenicity (VaxiJen 2.0), and physico-chemical parameters (ProtParam). Based on in silico predictions, out of 60 possible SLPs, 36 candidate structures presented a high probability to be immunogenic, non-allergenic, non-toxic, and stable. 3D peptide folding followed by 3D structure validation (PROCHECK) and molecular docking studies (HADDOCK 2.4) with Toll-like receptors 2 and 4 provided positive results, suggestive for favorable antigen presentation and immune stimulation. |
| first_indexed | 2024-03-09T20:54:53Z |
| format | Article |
| id | doaj.art-d0403a9002a346bd9d8fac2252a7b0a9 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T20:54:53Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-d0403a9002a346bd9d8fac2252a7b0a92023-11-23T22:25:25ZengMDPI AGVaccines2076-393X2022-01-0110221810.3390/vaccines10020218Cytotoxic T-Cell-Based Vaccine against SARS-CoV-2: A Hybrid Immunoinformatic ApproachAlexandru Tirziu0Virgil Paunescu1Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, RomaniaFaculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, RomaniaThis paper presents an alternative vaccination platform that provides long-term cellular immune protection mediated by cytotoxic T-cells. The immune response via cellular immunity creates superior resistance to viral mutations, which are currently the greatest threat to the global vaccination campaign. Furthermore, we also propose a safer, more facile, and physiologically appropriate immunization method using either intranasal or oral administration. The underlying technology is an adaptation of synthetic long peptides (SLPs) previously used in cancer immunotherapy. The overall quality of the SLP constructs was validated using in silico methods. SLPs comprising HLA class I and class II epitopes were designed to stimulate antigen cross-presentation and canonical class II presentation by dendritic cells. The desired effect is a cytotoxic T cell-mediated prompt and specific immune response against the virus-infected epithelia and a rapid and robust virus clearance. Epitopes isolated from COVID-19 convalescent patients were screened for HLA class I and class II binding (NetMHCpan and NetMHCIIpan) and highest HLA population coverage (IEDB Population Coverage). 15 class I and 4 class II epitopes were identified and used for this SLP design. The constructs were characterized based on their toxicity (ToxinPred), allergenicity (AllerCatPro), immunogenicity (VaxiJen 2.0), and physico-chemical parameters (ProtParam). Based on in silico predictions, out of 60 possible SLPs, 36 candidate structures presented a high probability to be immunogenic, non-allergenic, non-toxic, and stable. 3D peptide folding followed by 3D structure validation (PROCHECK) and molecular docking studies (HADDOCK 2.4) with Toll-like receptors 2 and 4 provided positive results, suggestive for favorable antigen presentation and immune stimulation.https://www.mdpi.com/2076-393X/10/2/218SARS-CoV-2 T-Cell vaccineepitopescytotoxic T lymphocyteslong term immunityacquired immunitymolecular docking |
| spellingShingle | Alexandru Tirziu Virgil Paunescu Cytotoxic T-Cell-Based Vaccine against SARS-CoV-2: A Hybrid Immunoinformatic Approach Vaccines SARS-CoV-2 T-Cell vaccine epitopes cytotoxic T lymphocytes long term immunity acquired immunity molecular docking |
| title | Cytotoxic T-Cell-Based Vaccine against SARS-CoV-2: A Hybrid Immunoinformatic Approach |
| title_full | Cytotoxic T-Cell-Based Vaccine against SARS-CoV-2: A Hybrid Immunoinformatic Approach |
| title_fullStr | Cytotoxic T-Cell-Based Vaccine against SARS-CoV-2: A Hybrid Immunoinformatic Approach |
| title_full_unstemmed | Cytotoxic T-Cell-Based Vaccine against SARS-CoV-2: A Hybrid Immunoinformatic Approach |
| title_short | Cytotoxic T-Cell-Based Vaccine against SARS-CoV-2: A Hybrid Immunoinformatic Approach |
| title_sort | cytotoxic t cell based vaccine against sars cov 2 a hybrid immunoinformatic approach |
| topic | SARS-CoV-2 T-Cell vaccine epitopes cytotoxic T lymphocytes long term immunity acquired immunity molecular docking |
| url | https://www.mdpi.com/2076-393X/10/2/218 |
| work_keys_str_mv | AT alexandrutirziu cytotoxictcellbasedvaccineagainstsarscov2ahybridimmunoinformaticapproach AT virgilpaunescu cytotoxictcellbasedvaccineagainstsarscov2ahybridimmunoinformaticapproach |