Design of a Multi-Epitopes Based Chimeric Vaccine against Enterobacter cloacae Using Pan-Genome and Reverse Vaccinology Approaches
Abstract
:1. Introduction
2. Material and Methods
2.1. A Prescreening Process for Proteome Extraction and Sub-Cellular Localization
2.2. Predicting Pathogenic Proteins—A Vaccine Candidate Prioritizing Stage in the Early Development Stage
2.3. Mapping T Cell Epitopes Obtained from B Cells
2.4. Designing and Evaluating the MEBEPV Systems
2.5. Immuno-Profiling of Universal MEBEPVs In Silico
2.6. Docking and Enhancement of MEBEPVs Using Blind Docking
2.7. CABS-Flex and Aggregation-Prone Zone Investigations
2.8. Molecular Dynamics Simulation (MDS) as a Method of Testing
2.9. Immune Receptors-MEBEPV Complexes Were Subjected to Binding Free Energy Measurements in Order to Determine Their Binding Affinity
3. Results
3.1. Pan Genome Analysis and Retrieval of the Core Proteome
3.2. Physiochemical Characterization and Evaluation of E. cloacae Being Antigenic
3.3. Epitopes Prediction Phase
3.4. Globall Population Coverage of the MHC I and MHC II Molecules
3.5. Physiochemical Properties and the Design of the MEBEPV
3.6. Structure Prediction and Refinement
3.7. Analysis of the CABS-Flex and Aggregation-Prone Regions
3.8. Disulfide Engineering, In Silico Cloning, and C-Immune Simulation
3.9. Binding Analysis of the Designed Vaccine to MHC-I, MHC-II, and TLR-3
3.10. MDs Simulation of TLRs-MEBEPV Complexes
3.11. Free Binding Energies
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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Accession No | Protein | T.Helices | MW | Instability Index | Antigenicity 0.7 | Adhesion 0.6 | Allergenisity | Solubility | Blastp (Human) | Blastp (Lactobacillus) |
---|---|---|---|---|---|---|---|---|---|---|
BBS36577.1 | Phosphoporin PhoE | 1 | 40.285.2 | 10.49 | 0.8008 | 0.896 | Non-allergen | Soluble | No similarity Found | No similarity Found |
WP_038419991.1 | Porin | 0 | 39.92468 | 17.82 | 0.7422 | 0.633 | Non-allergen | Soluble | No similarity Found | No similarity Found |
Proteins | B Cell Epitopes | MHC I | P.Rank | MHC II | P.Rank | MHC Pred | Score | Antigenisity | Allergenicity |
---|---|---|---|---|---|---|---|---|---|
Phosphoporin PhoE | YQGKNDRTDV KTANGDGVGY | KNDRTDVKTANG | 28 | KNDRTDVKTA | 7.8 | KNDRTDVKT | 13.06 | 1.7238 | non-allergen |
SYSNANRTLKQK ADGEGDKAEA | KADGEGDKAEA | 37 | KADGEGDKA | 3.4 | KADGEGDKA | 42.95 | 3.0005 | non-allergen | |
AETRNTTRTGT DGDAGFANKT | TGTDGDAGFANKT | 14 | DGDAGFANKT | 13 | DGDAGFANK | 65.31 | 0.919 | non-allergen | |
Porin | YQGKNDNRNE FKANGDG | YQGKNDNRNEF | 47 | YQGKNDNRNE | 24 | QGKNDNRNE | 59.29 | 2.3164 | non-allergen |
QGKDLYARNG YKGVDAD | GKDLYARNGYKGVD | 16 | KDLYARNGYK | 0.07 | KDLYARNGY | 36.56 | 1.203 | non-allergen | |
NLLDEEDGAIT GNATD | NLLDEEDGAITGN | 33 | LLDEEDGAI | 1.16 | LLDEEDGAI | 36.81 | 0.8689 | non-allergen |
Model | GDT-HA | RMSD | Molprobity | Clash Score | Poor Rotamers | Rama Favored |
---|---|---|---|---|---|---|
Initial | 1 | 0 | 2.945 | 46.7 | 2.5 | 91.7 |
MODEL 1 | 0.9339 | 0.444 | 1.8 | 11.1 | 1.3 | 97.1 |
MODEL 2 | 0.9471 | 0.418 | 1.654 | 9.2 | 1.3 | 97.6 |
MODEL 3 | 0.9315 | 0.476 | 1.74 | 9.5 | 1.3 | 97.1 |
MODEL 4 | 0.9339 | 0.46 | 1.627 | 8.6 | 1.3 | 97.6 |
MODEL 5 | 0.9435 | 0.435 | 1.604 | 9.8 | 0.6 | 97.6 |
Docking Statistics | Global Energy | Attractive VdW | Repulsive VdW | Atomic Contact Energy | Hydrogen Bond Energy |
---|---|---|---|---|---|
MHC I | −18.64 | −32.11 | 11.75 | 3.46 | −2.04 |
MHC II | −48.25 | −40.61 | 25.59 | 2.59 | −1.70 |
TLR3 | −5.20 | −28.10 | 13.08 | 17.38 | −7.28 |
Energy Parameter | TLR3-Vaccine Complex | MHC I-Vaccine Complex | MHC II-Vaccine Complex |
---|---|---|---|
MM-GBSA | |||
VDWAALS | −67.64 | −69.55 | −97.10 |
EEL | −85.24 | −81.32 | −115.17 |
Delta G gas | −149.88 | −150.87 | −212.27 |
Delta G solv | 27.71 | 25.47 | 24.33 |
Delta Total | −122.17 | −125.4 | −187.94 |
MM-PBSA | |||
VDWAALS | −67.64 | −69.55 | −97.10 |
EEL | −85.24 | −81.32 | −115.17 |
Delta G gas | −149.88 | −150.87 | −212.27 |
Delta G solv | 34.25 | 32.68 | 27.66 |
Delta Total | −115.63 | −118.19 | −184.61 |
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Al-Megrin, W.A.I.; Karkashan, A.; Alnuqaydan, A.M.; Aba Alkhayl, F.F.; Alrumaihi, F.; Almatroudi, A.; Allemailem, K.S. Design of a Multi-Epitopes Based Chimeric Vaccine against Enterobacter cloacae Using Pan-Genome and Reverse Vaccinology Approaches. Vaccines 2022, 10, 886. https://doi.org/10.3390/vaccines10060886
Al-Megrin WAI, Karkashan A, Alnuqaydan AM, Aba Alkhayl FF, Alrumaihi F, Almatroudi A, Allemailem KS. Design of a Multi-Epitopes Based Chimeric Vaccine against Enterobacter cloacae Using Pan-Genome and Reverse Vaccinology Approaches. Vaccines. 2022; 10(6):886. https://doi.org/10.3390/vaccines10060886
Chicago/Turabian StyleAl-Megrin, Wafa Abdullah I., Alaa Karkashan, Abdullah M. Alnuqaydan, Faris F. Aba Alkhayl, Faris Alrumaihi, Ahmad Almatroudi, and Khaled S. Allemailem. 2022. "Design of a Multi-Epitopes Based Chimeric Vaccine against Enterobacter cloacae Using Pan-Genome and Reverse Vaccinology Approaches" Vaccines 10, no. 6: 886. https://doi.org/10.3390/vaccines10060886
APA StyleAl-Megrin, W. A. I., Karkashan, A., Alnuqaydan, A. M., Aba Alkhayl, F. F., Alrumaihi, F., Almatroudi, A., & Allemailem, K. S. (2022). Design of a Multi-Epitopes Based Chimeric Vaccine against Enterobacter cloacae Using Pan-Genome and Reverse Vaccinology Approaches. Vaccines, 10(6), 886. https://doi.org/10.3390/vaccines10060886