Annotation of Potential Vaccine Targets and Design of a Multi-Epitope Subunit Vaccine against Yersinia pestis through Reverse Vaccinology and Validation through an Agent-Based Modeling Approach
Abstract
:1. Introduction
2. Materials and Methods
2.1. Retrieval of Proteomes
2.2. Removal of Homologous Proteins
2.3. Removal of Paralogous Proteins
2.4. Non-Essential Protein Removal
2.5. Subcellular Localization of Proteins
2.6. Prioritizing Potential Vaccine Candidates
2.7. Collection of Virulent Proteins
2.8. Antigenicity of the Proteins
2.9. Prioritization of Proteins
2.10. Epitope Prediction
2.11. Vaccine Construct Design
2.12. Allergenicity Prediction
2.13. Antigenicity Evaluation
2.14. Evaluation of Physiochemical Parameters
2.15. Homology Modeling of the Vaccine Construct
2.16. Tertiary Structure Refinement
2.17. Structure Validation
2.18. B-Cell Epitope Prediction
2.19. Molecular Docking of the Vaccine Constructs and TLR-4
2.20. Molecular Dynamics Simulation
2.21. Codon Optimization and Cloning of the Vaccine Construct
2.22. Immune Simulation
3. Results
3.1. Retrieval of Proteomes
3.2. Removal of Homologous Proteins
3.3. Removal of Paralogous Proteins
3.4. Removal of Non-Essential Proteins
3.5. Subcellular Localization
3.6. Collection of Virulent Proteins
3.7. Antigenicity and Physiochemical Properties of the Selected Vaccine Targets
3.8. CTL and HTL Epitope Prediction
3.9. B-Cell Epitope Prediction
3.10. Vaccine Construct Design
3.11. D Structure Prediction Using Robetta
3.12. Refinement of the Vaccine Tertiary Structure
3.13. Vaccine 3D Structure Validation
3.14. Physiochemical Properties of the Final Vaccine
3.15. Secondary Structure Prediction
3.16. Analysis of Vaccine Construct Interaction with TLRs
3.17. Molecular Simulations of TLR–Vaccine Complexes
3.18. Codon Optimization and Cloning of the Vaccine Construct
3.19. Immune Simulation
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | Protein | Virulence (Bit Score) | Virulence Sequence Identity | Antigenicity | Mass | Length |
---|---|---|---|---|---|---|
rstB | Sensor kinase protein | 182 bits | 33% | 0.6925 | 48,250 Da | 425 |
YPO2385 | Putative exported protein | 61.2 bits | 34% | 0.7901 | 32,315 Da | 288 |
hmuR | Hemin receptor | 886 bits | 68% | 0.6496 | 74,230 Da | 676 |
flaA1 | Flagellin | 97.4 bits | 40% | 0.7208 | 42,701 Da | 404 |
psaB | Chaperone protein PsaB | 531 bits | 100% | 0.6251 | 30,648 Da | 273 |
Protein Name | Epitopes | Sequence | Combined Score |
---|---|---|---|
Sensor kinase protein | CTL | RTPLVRLRY | 3.1800 |
CTL | MAMLVGLVY | 3.1360 | |
Putative exported protein | CTL | CSGLIYYAY | 2.6220 |
Hemin receptor | CTL | QSLSANLRY | 3.0050 |
CTL | SSSTPQAGY | 3.0610 | |
Flagellin | CTL | ETPKAVNEY | 2.6930 |
Chaperone protein PsaB | CTL | SADSLTWRY | 2.7150 |
CTL | PTPFYMNFY | 2.5490 |
Protein | Allele | Start–End | Peptide Sequence | Method | Percentile Rank | Antigenicity Score |
---|---|---|---|---|---|---|
Sensor kinase protein | HLA-DRB5 * 01:01 | 142–156 | LPVFLWMRPHWKDLL | Consensus (smm/nn/sturniolo) | 0.6 | 0.432 |
HLA-DRB3 * 02:02 | 404–418 | GGASFRFSWPIKTHL | NetMHCIIpan | 1.4 | 1.043 | |
HLA-DRB1 * 03:01 | 362–376 | EPFVRLDPSRDRATG | Consensus (smm/nn/sturniolo) | 1.6 | 0.564 | |
Putative exported protein | HLA-DRB3 * 02:02 | 207–221 | NEMYHLRDAAPVKRT | NetMHCIIpan | 5.1 | 1.042 |
HLA-DRB5 * 01:01 | 161–175 | AMSKLMKQVGKPYRW | Consensus (smm/nn/sturniolo) | 9.7 | 0.613 | |
Hemin receptor | HLA-DRB1 * 03:01 | 283–297 | RSTIQRDAQLRYNIK | Consensus (smm/nn/sturniolo) | 0.14 | 0.443 |
HLA-DRB1 * 07:01 | 340–354 | NRTRLFIESPASHLL | Consensus (comb.lib./smm/nn) | 0.54 | 0.480 | |
HLA-DRB1 * 15:01 | 434–448 | TDWLMLFGSYAQAFR | Consensus (smm/nn/sturniolo) | 0.86 | 0.679 | |
Flagellin | HLA-DRB1 * 07:01 | 25–39 | NAKSSQRLSTGFRIN | Consensus (comb.lib./smm/nn) | 3.1 | 0.461 |
HLA-DRB1 * 15:01 | 382–392 | QSSVMMLKKANAATQ | Consensus (smm/nn/sturniolo) | 7.9 | −0.444 | |
Chaperone protein PsaB | HLA-DRB5 * 01:01 | 89–103 | APFIVTPPLFRLDAG | Consensus (smm/nn/sturniolo) | 0.77 | 0.722 |
HLA-DRB1 * 15:01 | 181–195 | ADSLTWRYKGNYLEV | Consensus (smm/nn/sturniolo) | 4.2 | 0.504 |
Protein | Sequence | Starting Position | Score |
---|---|---|---|
Chaperone protein PsaB | APFIVTPPLFRLDAGL | 89 | 0.95 |
CLTGIPPKNGDAWGNT | 128 | 0.94 | |
YPSSSTKGVSVSVANP | 54 | 0.91 | |
SLTWRYKGNYLEVNNP | 183 | 0.90 | |
Histidine kinase | SWPIKTHLPLSADQNV | 411 | 0.94 |
SGHLDERTHFDPTSSL | 167 | 0.91 | |
YERPE Hemin receptor | PVSILAGTRYDNYSGS | 396 | 0.94 |
YETVDAADMLQPGQNS | 164 | 0.93 | |
KDYISTRVDMQAMTTT | 520 | 0.92 | |
SRVSSSTPQAGYGVND | 612 | 0.91 | |
NWDLAYNRTRGKNQNT | 559 | 0.91 | |
TRDIGNIRQSNGFNAP | 215 | 0.91 | |
GLTLTNYWVPNPNLKP | 469 | 0.90 | |
PTMGEMYNDSKHFAIP | 450 | 0.90 | |
SGSSDGYADVDADKWS | 409 | 0.90 | |
GWLQDEITLRDLPVSI | 384 | 0.90 | |
ARPQGSAEEGREQTTE | 319 | 0.90 | |
YERPE Flagellin | SDVIDAYGAFRATLGA | 321 | 0.95 |
GFRINSPADNAAGLQI | 35 | 0.93 | |
LGSIKDTDFADEMKNH | 359 | 0.92 | |
KQEIETPKAVNEYVVK | 280 | 0.92 | |
AESVKTLNAMKKLATQ | 359 | 0.91 | |
Putative exported protein | HVSQASPDDRKKRKAD | 41 | 0.96 |
GPVSKKTTEPRKTGNN | 69 | 0.93 | |
SGLIYYAYKDVVKIKM | 187 | 0.92 | |
GKFIQSPRTGEEIRIS | 249 | 0.91 | |
TSSIRTAKTPYGRQRN | 113 | 0.9 |
Model | GDT-HA | RMSD | MolProbity | Clash Score | Poor Rotamers | Rama Favored |
---|---|---|---|---|---|---|
MODEL 1 | 0.949 | 0.42 | 1.42 | 7.81 | 0.62 | 98.31 |
MODEL 2 | 0.958 | 0.40 | 1.40 | 7.31 | 0.61 | 98.54 |
MODEL 3 | 0.948 | 0.42 | 1.46 | 8.72 | 0.92 | 98.32 |
MODEL 4 | 0.961 | 0.39 | 1.46 | 8.63 | 0.64 | 98.52 |
MODEL 5 | 0.943 | 0.42 | 1.46 | 8.61 | 0.66 | 98.33 |
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Haq, A.U.; Khan, A.; Khan, J.; Irum, S.; Waheed, Y.; Ahmad, S.; Nizam-Uddin, N.; Albutti, A.; Zaman, N.; Hussain, Z.; et al. Annotation of Potential Vaccine Targets and Design of a Multi-Epitope Subunit Vaccine against Yersinia pestis through Reverse Vaccinology and Validation through an Agent-Based Modeling Approach. Vaccines 2021, 9, 1327. https://doi.org/10.3390/vaccines9111327
Haq AU, Khan A, Khan J, Irum S, Waheed Y, Ahmad S, Nizam-Uddin N, Albutti A, Zaman N, Hussain Z, et al. Annotation of Potential Vaccine Targets and Design of a Multi-Epitope Subunit Vaccine against Yersinia pestis through Reverse Vaccinology and Validation through an Agent-Based Modeling Approach. Vaccines. 2021; 9(11):1327. https://doi.org/10.3390/vaccines9111327
Chicago/Turabian StyleHaq, Azaz Ul, Abbas Khan, Jafar Khan, Shamaila Irum, Yasir Waheed, Sajjad Ahmad, N. Nizam-Uddin, Aqel Albutti, Nasib Zaman, Zahid Hussain, and et al. 2021. "Annotation of Potential Vaccine Targets and Design of a Multi-Epitope Subunit Vaccine against Yersinia pestis through Reverse Vaccinology and Validation through an Agent-Based Modeling Approach" Vaccines 9, no. 11: 1327. https://doi.org/10.3390/vaccines9111327