Vaccinomics-Aided Development of a Next-Generation Chimeric Vaccine against an Emerging Threat: Mycoplasma genitalium
Abstract
:1. Introduction
2. Materials and Methods
2.1. Retrieval of M. genitalium Reference Proteome
2.2. Epitope Mapping
2.3. Conserved Epitope Analysis
2.4. Epitopes Assembly
2.5. Profiling of Immunogenicity, Allergenicity, and Physicochemical Characteristics
2.6. Solubility Analysis
2.7. Computation of Secondary Structure
2.8. Computation of Tertiary Structure (3D)
2.9. 3D Model Validation and Refinement
2.10. Probing of Discontinuous BCEs
2.11. Docking Studies of the Modeled Vaccine with Toll-like Receptors
2.12. Energy Optimization and Simulation of Molecular Dynamics
2.13. Simulated Immune Responses
2.14. Reverse Transcription and Computational Cloning into Vector Backbone
3. Results
3.1. Finalization of Protein Sequences for Development of Vaccine Based on Immunogenicity Analysis
3.2. Finalization of Cytotoxic T-Lymphocyte Epitopes
3.3. Identification of Helper T-Lymphocyte Epitopes
3.4. Probing the Linear BCEs
3.5. Fusion of Final Candidates
3.6. Physicochemical and Antigenicity Profiling of Chimeric Construct
3.7. Solubility Analysis
3.8. Projection of Vaccine’s 2-D Structure
3.9. 3D Modeling of the Proposed Construct
3.10. 3D Model Enhancement and Quality Inspection
3.11. Probing Non-Linear BCEs
3.12. Docking Studies of the Modeled Vaccine with Toll-like Receptors
3.13. Binding Energy Analysis
3.14. MD Simulations
3.15. Immune Simulations
4. Discussions
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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Uniprot Entry Identifier | Protein | Antigenicity (VaxiJen) | Non-Allergen | Subcellular Localization | |
---|---|---|---|---|---|
1 | P47377 | MG131 (Hypothetical protein) | 1.16 | Yes | Cytoplasmic membrane |
2 | P58061 | SECG (Probable protein-export membrane protein SecG) | 0.93 | Yes | Cytoplasmic membrane |
3 | P47489 | PLSY (Glycerol-3-phosphate acyltransferase) | 0.92 | Yes | Cytoplasmic membrane |
4 | P47286 | MG040 (ABC transporter substrate binding protein pnrA-like) | 0.76 | Yes | Cytoplasmic membrane |
5 | P47502 | MG260 (Mycoplasma lipoprotein) | 0.76 | Yes | Cytoplasmic Membrane |
6 | Q49417 | P32 adhesin | 0.69 | Yes | Cytoplasmic Membrane |
7 | P20796 | Adhesin P1 | 0.52 | Yes | Cytoplasmic Membrane |
Protein ID | CTL Epitopes (9-mer) | MHC Class(I) Supertypes | Binding Affinity | VaxiJen Score | Non-Allergen | Toxicity | Conservation |
---|---|---|---|---|---|---|---|
P47377 | YSALIPLFI | A1, A24 | 0.24 | 1.8319 | Yes | No | 100% |
P58061 | AVICLIIGL | A1, A2 | 0.57 | 0.82 | Yes | No | 100% |
P47489 | YQSTYFLSY | A3, A24 | 0.17 | 1.22 | Yes | No | 100% |
P47286 | YIIWELIPF | A1, A24 | 0.11 | 2.1807 | Yes | No | 100% |
P47502 | SVTLEQGWY | A2, A3, A24 | 0.46 | 0.82 | Yes | No | 100% |
Protein ID | HTL Epitopes (15-mer) | Percentile Rank | IC50 | VaxiJen Score | Non-Allergen | Toxicity | Conser- Vation |
---|---|---|---|---|---|---|---|
P47377 | ALIPLFILLISLVLF | 0.01 | 0.21 | 2.11 | Yes | No | 100% |
P58061 | GFVKILQIIMFILVV | 0.02 | 0.32 | 0.82 | Yes | No | 100% |
P47489 | EKVYQSTYFLSYLSC | 0.04 | 0.41 | 0.59 | Yes | No | 100% |
P47286 | FDLVLLWFLFVPLLI | 0.01 | 0.69 | 3.53 | Yes | No | 100% |
P47502 | AKKAFRLYKKKISTS | 0.03 | 0.81 | 0.51 | Yes | No | 100% |
P20796 | KLVLFLLAIVFLMLG | 0.15 | 0.95 | 1.29 | Yes | No | 100% |
No. | Residues | Total Residues | Score |
---|---|---|---|
1 | A:M1, A:A2, A:K3, A:L4, A:S5, A:T6, A:D7, A:E8, A:L9, A:L10, A:D11, A:A12, A:F13, A:K14, A:E15, A:M16, A:T17, A:L18, A:L19, A:E20, A:L21, A:S22, A:D23, A:F24, A:V25, A:K26, A:K27, A:F28, A:E29, A:E30, A:T31, A:F32, A:E33, A:V34, A:T35, A:A36, A:A37, A:A38, A:P39, A:V40, A:A41, A:V42, A:A43, A:A44, A:A45, A:G46, A:A47, A:A48, A:P49, A:P381 | 50 | 0.841 |
2 | A:E68, A:A69, A:G71, A:D72, A:K73, A:I75, A:G76, A:V77, A:I78, A:K79, A:V80, A:V81, A:R82, A:E83, A:I84, A:V85, A:S86, A:G87, A:L88, A:G89, A:L90, A:K91, A:E92, A:A93, A:K94, A:D95, A:L96, A:V97, A:D98, A:G99, A:A100, A:P101, A:K102, A:P103, A:L104, A:L105, A:E106, A:K107, A:V108, A:A109, A:K110, A:E111, A:A112, A:A113, A:D114, A:E115, A:A116, A:K117, A:A118, A:L120, A:E121, A:A122, A:G124, A:A125, A:T126, A:T128, A:K290, A:K291, A:I292, A:S293, A:T294, A:S295, A:G296, A:P297, A:G298, A:P299, A:G300, A:K301, A:L302, A:V303, A:L304, A:F305, A:L306, A:A308, A:I309, A:V310, A:L312, A:M313, A:L314, A:G315, A:F316, A:S317 | 82 | 0.699 |
3 | A:W178, A:E179, A:L180, A:I181, A:P182, A:F183, A:A184, A:A185, A:K186, A:S187, A:V188, A:T189, A:L190, A:E191, A:Q192, A:G193, A:W194, A:Y195, A:G196, A:P197, A:G198, A:P199, A:G200, A:A201, A:I207, A:S211, A:L212, A:V213, A:L214, A:F215, A:G216, A:P217, A:G218, A:P219, A:F222, A:V223, A:K224, A:I225, A:L226, A:Q227, A:I228, A:I229, A:M230, A:F231, A:I232, A:L233, A:V234, A:V235, A:G236, A:P237, A:G238, A:P239, A:G240, A:E241, A:K242, A:V243, A:Y244, A:Q245, A:S246, A:T247, A:Y248, A:F249, A:L250, A:S251, A:Y252, A:L253, A:S254, A:C255, A:G256, A:P257, A:G258, A:P259, A:G260, A:F261, A:D262, A:L263, A:L266, A:W267 | 78 | 0.687 |
4 | A:D64, A:V65, A:I66, A:E334 | 4 | 0.576 |
5 | A:K130, A:A132, A:A133, A:A134, A:K135, A:Y139 | 6 | 0.56 |
Vaccine Construct | TLRs | Solution | a GBE | b aVdW | c HBE | d ACE | e Score | f Area |
TLR 1 | 1 | −37.53 | −40.86 | −2.37 | 4.44 | 20,226 | 3124.50 | |
TLR 2 | 7 | −12.41 | −52.34 | −3.94 | −0.55 | 17,078 | 2019.00 | |
TLR 6 | 4 | −7.79 | −24.19 | −5.19 | 8.37 | 15,410 | 2584.60 |
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Khalid, K.; Hussain, T.; Jamil, Z.; Alrokayan, K.S.; Ahmad, B.; Waheed, Y. Vaccinomics-Aided Development of a Next-Generation Chimeric Vaccine against an Emerging Threat: Mycoplasma genitalium. Vaccines 2022, 10, 1720. https://doi.org/10.3390/vaccines10101720
Khalid K, Hussain T, Jamil Z, Alrokayan KS, Ahmad B, Waheed Y. Vaccinomics-Aided Development of a Next-Generation Chimeric Vaccine against an Emerging Threat: Mycoplasma genitalium. Vaccines. 2022; 10(10):1720. https://doi.org/10.3390/vaccines10101720
Chicago/Turabian StyleKhalid, Kashaf, Tajamul Hussain, Zubia Jamil, Khalid Salman Alrokayan, Bashir Ahmad, and Yasir Waheed. 2022. "Vaccinomics-Aided Development of a Next-Generation Chimeric Vaccine against an Emerging Threat: Mycoplasma genitalium" Vaccines 10, no. 10: 1720. https://doi.org/10.3390/vaccines10101720
APA StyleKhalid, K., Hussain, T., Jamil, Z., Alrokayan, K. S., Ahmad, B., & Waheed, Y. (2022). Vaccinomics-Aided Development of a Next-Generation Chimeric Vaccine against an Emerging Threat: Mycoplasma genitalium. Vaccines, 10(10), 1720. https://doi.org/10.3390/vaccines10101720