Designing a Candidate Multi-Epitope Vaccine against Transmissible Gastroenteritis Virus Based on Immunoinformatic and Molecular Dynamics
Abstract
:1. Introduction
2. Results
2.1. Conservative Analysis of TGEV S Protein and Selection of Vaccine Strain
2.2. S Protein Structure Simulation and Glycosylation Site Prediction
2.3. Prediction and Analysis of B Cell Epitopes
2.4. T Cell Epitopes Prediction
2.5. Design of Multi-Epitope Vaccine Candidate
2.6. Antigenicity, Allergenicity, and Physicochemical Properties Evaluation of Vaccine Candidate
2.7. Secondary and Tertiary Structure Prediction of Vaccine
2.8. Prediction of Conformational B Cell Epitopes
2.9. Molecular Docking with TLR4
2.10. Molecular Dynamic Simulation
2.11. Simulation of Immune Responses
2.12. Optimization of Codons and In Silico Cloning
3. Discussion
4. Materials and Methods
4.1. Sequence Datasets and Phylogenetic Tree Analysis
4.2. Tertiary Structure Simulation and N-Glycosylation Site Prediction of TGEV S Protein
4.3. Prediction of B Cell Epitopes
4.4. T Cell Epitope Prediction
4.5. Molecular Docking of CD8 T Cell Epitopes with SLA Alleles
4.6. Antigenicity, Allergenicity, Toxicity, and Conservation Analysis
4.7. Construction of the Vaccine, Structure Modelling, and Validation
4.8. Secondary and Tertiary Structure Prediction
4.9. Prediction of Conformational B Cell Epitopes
4.10. Molecular Docking of Vaccine with TLR4 and Molecular Dynamic Simulation
4.11. Simulation of Immune Responses against Designed Vaccines
4.12. Codon Optimization and In Silico Cloning
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Epitope | Length | Position | Sequence | Toxin | Identity (62 Isolates) |
---|---|---|---|---|---|
B1 | 14 | 137–150 | PPTTTTESSLTCNW | Non-Toxin | 87.09% (55/62) |
B2 | 16 | 530–545 | NITIGLGMKRSGYGQP | Non-Toxin | 96.77% (60/62) |
B3 | 12 | 955–970 | YRSAIEDLLFDKVVTS | Non-Toxin | 93.54% (58/62) |
B4 | 18 | 968–985 | VTSGLGTVDEDYKRCTGG | Non-Toxin | 91.93% (57/62) |
B5 | 11 | 1186–1196 | VRSQSQRFGFC | Non-Toxin | 96.77% (60/62) |
B6 | 16 | 603–618 | IKTGTCPFSFDKLNNY | Non-Toxin | 85.48% (53/62) |
B7 | 8 | 802–809 | YSNIGVCK | Non-Toxin | 100.00% (62/62) |
B8 | 12 | 757–768 | SELLGLTHWTTT | Non-Toxin | 98.38% (61/62) |
Epitope | Length | Position | Sequence | Score | Rank | TAP Score | Proteasome Score | MHC Ⅰ IC50 (nM) | Toxin | Identity (62 Isolates) |
---|---|---|---|---|---|---|---|---|---|---|
CTL1 | 9 | 275–283 | FSFNNWFLL | 0.90876 | 0.15 | 0.43 | 1.79 | 307.9 | Non-Toxin | 100.00% (62/62) |
CTL2 | 9 | 391–399 | VTDGPRYCY | 0.968509 | 0.02 | 1.2 | 2.75 | 62.2 | Non-Toxin | 93.54% (58/62) |
CTL3 | 9 | 421–429 | AISKWGHFY | 0.871218 | 0.07 | 1.39 | 2.68 | 42.3 | Non-Toxin | 96.77% (60/62) |
CTL4 | 9 | 724–732 | VSDGVIYSV | 0.776052 | 0.23 | 1.25 | 1.32 | 210.6 | Non-Toxin | 100.00% (62/62) |
CTL5 | 9 | 766–774 | TTTPNFYYY | 0.745044 | 0.17 | 1.21 | 1.54 | 67.7 | Non-Toxin | 100.00% (62/62) |
CTL6 | 9 | 988–996 | IADLVCAQY | 0.880338 | 0.06 | 1.17 | 1.46 | 90.8 | Non-Toxin | 100.00% (62/62) |
CTL7 | 9 | 1187–1195 | RSQSQRFGF | 0.418621 | 0.04 | 1.15 | 1.22 | 148.8 | Non-Toxin | 100.00% (62/62) |
CTL8 | 9 | 1329–1337 | TFDIFNATY | 0.818436 | 0.12 | 1.35 | 1.28 | 98 | Non-Toxin | 96.77% (60/62) |
Epitope | Length | Position | Sequence | Rank | IL-4 | IFN | MHC Ⅱ IC50 (nM) | Toxin | Identity (62 Isolates) |
---|---|---|---|---|---|---|---|---|---|
Th1 | 15 | 428–442 | FYINGYNFFSTFPID | 0.84 | IL4-inducer | Positive | 45.63 | Non-Toxin | 91.93% (57/62) |
Th2 | 15 | 513–527 | VNKSVVLLPSFYTHT | 0.37 | IL4-inducer | Positive | 32.82 | Non-Toxin | 85.48% (53/62) |
Th3 | 15 | 766–780 | TTTPNFYYYSIYNYT | 2.9 | IL4-inducer | Positive | 160.09 | Non-Toxin | 100.00% (62/62) |
Th4 | 15 | 796–810 | CEPVITYSNIGVCKN | 1.1 | IL4-inducer | Positive | 31.1 | Non-Toxin | 100.00% (62/62) |
Th5 | 15 | 837–851 | TNFTISVQVEYIQVY | 3.9 | IL4-inducer | Positive | 192.33 | Non-Toxin | 98.38% (61/62) |
Th6 | 15 | 1375–1389 | LEWLNRIETYVKWPW | 5 | IL4-inducer | Positive | 63.01 | Non-Toxin | 100.00% (62/62) |
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Bai, Y.; Zhou, M.; Wang, N.; Yang, Y.; Wang, D. Designing a Candidate Multi-Epitope Vaccine against Transmissible Gastroenteritis Virus Based on Immunoinformatic and Molecular Dynamics. Int. J. Mol. Sci. 2024, 25, 8828. https://doi.org/10.3390/ijms25168828
Bai Y, Zhou M, Wang N, Yang Y, Wang D. Designing a Candidate Multi-Epitope Vaccine against Transmissible Gastroenteritis Virus Based on Immunoinformatic and Molecular Dynamics. International Journal of Molecular Sciences. 2024; 25(16):8828. https://doi.org/10.3390/ijms25168828
Chicago/Turabian StyleBai, Yihan, Mingxia Zhou, Naidong Wang, Yi Yang, and Dongliang Wang. 2024. "Designing a Candidate Multi-Epitope Vaccine against Transmissible Gastroenteritis Virus Based on Immunoinformatic and Molecular Dynamics" International Journal of Molecular Sciences 25, no. 16: 8828. https://doi.org/10.3390/ijms25168828