Core Proteomics and Immunoinformatic Approaches to Design a Multiepitope Reverse Vaccine Candidate against Chagas Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. T. cruzi Core Proteome Identification
2.2. Subtractive Proteomics Approach
2.3. Epitopes Prediction and Assessment
2.3.1. Cytotoxic T-Cell Lymphocytes (CTLs)
2.3.2. Helper T-Lymphocytes (HTLs)
2.3.3. Linear B-Lymphocytes (LBLs)
2.4. T-Cell Epitope Population Coverage and Conservation Analysis
2.5. Modeling of Peptides and Molecular Docking
2.6. Construction of a Multi-Epitope Vaccine Candidate
2.7. Structural Analysis of Multi Epitope Reverse Vaccine (MERV) Construct
2.8. 3D Structure Prediction and Confirmation
2.9. Discontinuous B Cell Epitope Prediction
2.10. Disulfide Engineering for Vaccine Candidate
2.11. Molecular Docking
2.12. MD Simulation and Analysis in Normal Mode
2.13. Modeling the Immune System
2.14. Codon Optimization and In-Silico Cloning
3. Results
3.1. Examination of the Core Proteome
3.2. Identification of Interest Proteins
3.3. Prediction of Epitopes
3.4. T-Cell Epitope Population Coverage and Conservation Analysis
3.5. Epitope and Allele Docking Studies
3.6. The Core Properties and Structure of the Vaccine Candidate
3.7. Immunological Evaluation and Physicochemical Properties
3.8. 3D Structure Refinement
3.9. Conformational B Cell Epitopes Prediction
3.10. Disulfide Engineering for Vaccines
3.11. Molecular Docking Research
3.12. MD Simulation
3.13. Simulation of Immune Response
3.14. Codon Adaptation and In Silico Cloning
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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Name of Protein | Accession No. | Sub-Cellular Localization | Transmembrane Helices | Antigenicity | Molecular Weight (kDa) |
---|---|---|---|---|---|
Thiol transferase Tc52 | AAO63160.1 | Cytoplasmic | 0 | 0.4473 | 48.12 |
Ribosomal protein P0 | AAA30236.1 | Mitochondrial | 0 | 0.4933 | 34.95 |
TcP2beta | CAA52941.1 | Mitochondrial | 0 | 0.6152 | 10.57 |
Ribosomal protein P1 | AAT37631.1 | Plasma membrane | 0 | 0.6218 | 11.41 |
Protein Name | Epitopes | Interacting HLAs Number | Immunogenicity | Allergenicity | Antigenicity | Toxicity | Conservancy (Identity ≤ 100) | Remarks |
---|---|---|---|---|---|---|---|---|
Thiol transferase Tc52 | NPRETVPTL | 54 | Positive | Non-allergen | 0.8667 | Non-toxic | 100.00% (1/1) | Selected |
RVLITAKEK | 27 | Positive | Non-allergen | 0.8488 | Non-toxic | 100.00% (1/1) | ||
ESQLIVHYL | 27 | Positive | Non-allergen | 0.8358 | Non-toxic | 100.00% (1/1) | ||
FLGEIGDLV | 81 | Positive | Non-allergen | 1.5065 | Non-toxic | 100.00% (1/1) | Selected | |
Ribosomal protein P0 | SLGAGIPTA | 81 | Positive | Non-allergen | 0.9863 | Non-toxic | 100.00% (1/1) | |
EAKREYEER | 81 | Positive | Non-allergen | 1.1030 | Non-toxic | 100.00% (1/1) | Selected | |
YGRVLFCLM | 27 | Positive | Non-allergen | 0.7849 | Non-toxic | 100.00% (1/1) | ||
SEAKREYEER | 27 | Positive | Non-allergen | 1.0618 | Non-toxic | 100.00% (1/1) | Selected | |
TcP2beta | RPNAATASA | 54 | Positive | Non-allergen | 1.1933 | Non-toxic | 100.00% (1/1) | Selected |
TASAPTAAA | 27 | Positive | Non-allergen | 0.9171 | Non-toxic | 100.00% (1/1) | ||
AEEEEDDDMG | 27 | Positive | Non-allergen | 1.1749 | Non-toxic | 100.00% (1/1) | Selected | |
EEEDDDMGFG | 27 | Positive | Non-allergen | 0.8471 | Non-toxic | 100.00% (1/1) | ||
Ribosomal Protein P1 | VIFARFLEK | 27 | Positive | Non-allergen | 1.3362 | Non-toxic | 100.00% (1/1) | Selected |
LPVIFARFL | 27 | Positive | Non-allergen | 1.2247 | Non-toxic | 100.00% (1/1) | ||
VIFARFLEKK | 54 | Positive | Non-allergen | 1.3986 | Non-toxic | 100.00% (1/1) | Selected | |
TKEEEEDDDM | 27 | Positive | Non-allergen | 1.1196 | Non-toxic | 100.00% (1/1) |
Protein Name | Epitopes | No. of Interacting HLAs | IL10 | IL4 | Antigenicity | IFN-γ | Conservancy (Identity ≤ 100) | Remarks |
---|---|---|---|---|---|---|---|---|
Thiol transferase Tc52 | NVDYFMDAMYSFIKD | 81 | Inducer | Inducer | 0.8484 | Positive | 100.00% (1/1) | Selected |
SNVDYFMDAMYSFIK | 27 | Inducer | Inducer | 0.5137 | Positive | 100.00% (1/1) | ||
KCMIESDLISRYIDR | 27 | Inducer | Inducer | 0.7380 | Positive | 100.00% (1/1) | Selected | |
SYHVRFVESNVDYFM | 54 | Inducer | Inducer | 0.5797 | Positive | 100.00% (1/1) | ||
Ribosomal protein P0 | KHRVQAPARVGAIAP | 54 | Inducer | Inducer | 1.1816 | Positive | 100.00% (1/1) | Selected |
HRVQAPARVGAIAPC | 27 | Inducer | Inducer | 1.0619 | Positive | 100.00% (1/1) | Selected | |
PCDVIVPAGNTGMEP | 54 | Inducer | Inducer | 0.6644 | Positive | 100.00% (1/1) | ||
FKTLLGASVATEYEF | 27 | Inducer | Inducer | 0.4773 | Positive | 100.00% (1/1) | ||
TcP2beta | EGKSKLVGGVTRPNA | 54 | Inducer | Inducer | 0.8056 | Positive | 98.54% (38/39) | |
VGLSGGTPSKSAVEA | 27 | Inducer | Inducer | 1.2365 | Positive | 98.54% (38/39) | ||
GGTPSKSAVEAVLKA | 54 | Inducer | Inducer | 0.8458 | Positive | 100.00% (1/1) | Selected | |
VCTEGKSKLVGGVTR | 27 | Inducer | Inducer | 0.8138 | Positive | 100.00% (1/1) | Selected | |
Ribosomal Protein P1 | EGAAAAPAAGSAAPA | 27 | Inducer | Inducer | 0.8360 | Positive | 100.00% (1/1) | |
ARFLEKKPLETLFAA | 54 | Inducer | Inducer | 1.1755 | Positive | 100.00% (1/1) | Selected | |
GSAAPAAAAAGAAPA | 27 | Inducer | Inducer | 0.9713 | Positive | 100.00% (1/1) | Selected | |
TLPVIFARFLEKKPL | 27 | Inducer | Inducer | 0.7751 | Positive | 100.00% (1/1) |
Protein Name | Sequence | Score | Antigenicity | Allergenicity | Toxicity | Remarks |
---|---|---|---|---|---|---|
Thiol transferase Tc52 | PRETVPTLQVDG | 0.7874 | 1.1616 | Non-allergen | Non-toxic | Selected |
LNPRETVPTLQV | 0.7025 | 0.4951 | Non-allergen | Non-toxic | ||
SRYIDRISSPAN | 0.7828 | 0.5385 | Non-allergen | Non-toxic | ||
LMGSSPYQRHRV | 0.7522 | 1.0283 | Non-allergen | Non-toxic | Selected | |
Ribosomal protein P0 | EAKREYEERFNG | 0.8234 | 1.2682 | Non-allergen | Non-toxic | Selected |
SEAKREYEERFN | 0.8269 | 0.7628 | Non-allergen | Non-toxic | ||
ERFNGCLTKYGR | 0.8194 | 0.7035 | Non-allergen | Non-toxic | ||
KREYEERFNGCL | 0.7704 | 1.5208 | Non-allergen | Non-toxic | Selected | |
TcP2beta | GLSGGTPSKSAV | 0.6102 | 1.4848 | Non-allergen | Non-toxic | Selected |
LSGGTPSKSAVE | 0.6932 | 1.2704 | Non-allergen | Non-toxic | Selected | |
SGGTPSKSAVEA | 0.6109 | 1.1716 | Non-allergen | Non-toxic |
Selected T-Cell Epitopes | PDB IDs of HLAs/Receptors | Epitope Affinity (kcal/mol) | Control Affinity (kcal/mol) | Number of Hydrogens Bonds (CHB) | Residues Involved in CHB Networks |
---|---|---|---|---|---|
NPRETVPTL | 1a6a (HLA-DR3) | −7.3 | −6.9 | 8 (7) | Ala49, Trp7, Ile87, Gly19, Ile11, Ala29, Trp17, Tyr74 |
FLGEIGDLV | 1h15 (HLA-DRA1*0101) | −7.1 | −7.0 | 8 (7) | Thr80, Lys91, Val156, Tyr7, Lys84, Leu66, Thr77, Asn143 |
EAKREYEER | 2q6w (HLA- DRB3*0101) | −7.3 | −7.0 | 9 (7) | Lys26, Asn17, Asn77,Lys89, Tyr84,Tyr99,Thr343, Lys146, Trp34 |
SEAKREYEER | 2seb (HLA-DR4) | −6.9 | −7.1 | 7 (5) | Arg171, Ala12, Asn82, Val1, Glu6, Ser4, Thr77 |
RPNAATASA | 3c5 (HLA- (DRA*0101) | −7.3 | −7.5 | 9 (7) | Tyr17,Asp92,Asp99,Ser241, Lys66, Tyr99, Glu152, Glu152, Gln155 |
AEEEEDDDMG | 2fse (HLA-DRB1*0101) | −6.7 | −6.3 | 7 (6) | Glu80, Trp72, Asn326, Glu7, His145, Phe37, Ile17 |
VIFARFLEK | 1YDP (HLA-G) | −6.9 | −6.6 | 8 (5) | Lys80, Tyr84, Thr146, Val7, Lys9, Val66, Tyr77, Asn143 |
VIFARFLEKK | 2D31 (HLA-G) | −7.7 | −7.3 | 10 (8) | Lys80, Tyr84, Thr146, Val7, Lys9, Val66, Tyr77, Asn143, Val13, Thr14 |
NVDYFMDAMYSFIKD | 3C5J (HLA DR52c) | −7.1 | −6.3 | 9 (5) | Met69, Ile149, Thr7, Asn8, Ala19, Ile1, Gla2, Tyr7, Trp74 |
KCMIESDLISRYIDR | 1EU3 (HLA-E) | −7.0 | −6.8 | 8 (7) | Lys87, Tyr84, Tyr99, Lys149, Thr146, Ile147, Glu152, Glu154 |
KHRVQAPARVGAIAP | 3LQZ (HLA-DP2) | −6.8 | −6.0 | 7 (4) | Ser53, Glu89, Asn72, Ile17, His7, Glu45, Phe17 |
HRVQAPARVGAIAPC | 4GKZ (HA1.7) | −7.0 | −6.9 | 8 (7) | Arg71, Asn12, Ala82, Val17, Ser6, Glu4, Thr77, Thr13 |
GGTPSKSAVEAVLKA | 6J1V (HLA-A*3003/RT313) | −6.7 | −6.1 | 8 (5) | Tyr80, Lys84, Val146, Thr7, Lys9, Val66, Thr77, Asn143 |
VCTEGKSKLVGGVTR | 6J1V (HLA-A*3003/RT313) | −6.5 | −6.8 | 7 (5) | Asn82, Glu1, Glu6, Ser4, Thr79, Ile13, Val114 |
ARFLEKKPLETLFAA | 1KPR (HLA-E) | −7.1 | −7.0 | 7 (4) | Glu85, Trp326, Thr78, Glu45, Phe8, Ile17 |
GSAAPAAAAAGAAPA | 6Z9V(A02 allele) | −6.9 | −6.0 | 7 (5) | Lys146, Trp147, Glu15, Glu152, Tyr84, Tyr99, Thr143, |
Characteristics | Finding | Remark |
---|---|---|
Number of amino acids | 475 | Suitable |
Molecular weight | 49,607.54 | Suitable |
Theoretical pI | 8.53 | Base |
Chemical formula | C2201H3525N609O671S11 | - |
Instability index of vaccine | 27.83 | Stable |
Aliphatic index of vaccine | 71.89 | Thermostable |
Grand average of hydropathicity (GRAVY) | −0.352 | Hydrophilic |
Antigenicity | 0.6635 | Antigenic |
Immunogenicity | 1.08175 | Immunogenic |
Allergenicity | No | Non-allergen |
Solubility | 0.658 | Soluble |
Characters | SOPMA | PSIPRED Server | ||
---|---|---|---|---|
AA | % | AA | % | |
α helix | 241 | 50.74 | 232 | 48.84 |
β strand | 34 | 7.16 | 34 | 7.157 |
Random coil | 145 | 30.53 | 209 | 44 |
No. | Residues | Number of Residues | Score |
---|---|---|---|
1 | A: A182, A:A183, A:Y184 | 3 | 0.994 |
2 | A:M1, A:A2, A:K3, A:E164, A:Y165, A:E166, A:E167, A:R168, A:A169, A:A170, A:Y171, A:S172, A:E173, A:A174, A:K175, A:R176, A:E177, A:Y178, A:E179, A:E180, A:R181, A:R185, A:P186, A:N187, A:A188, A:A189, A:T190, A:A191, A:S192, A:A193, A:A194, A:A195, A:Y196, A:A197, A:E198, A:E199, A:E200, A:E201, A:D203, A:D204 | 40 | 0.833 |
3 | A:K393, A:P394, A:R395, A:E422, A:A423, A:K424, A:R425, A:E426, A:Y427, A:E428, A:E429, A:R430, A:F431, A:N432, A:G433, A:K434, A:K435, A:K436, A:R437, A:E438, A:Y439, A:E440, A:E441, A:R442, A:F443, A:N444, A:G445, A:C446, A:L447, A:K448, A:K449, A:G450, A:L451, A:S452, A:G453, A:G454, A:T455, A:P456, A:S457, A:K458, A:S459, A:A460, A:V461, A:K462, A:K463, A:L464, A:S465, A:G466, A:G467, A:T468, A:P469, A:S470, A:K471, A:S472, A:A473, A:V474, A:E475 | 57 | 0.775 |
4 | A:V25, A:K26, A:F28, A:E29, A:E30, A:T31, A:F32, 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:A50, A:G51, A:A52, A:A53, A:V54, A:E55, A:A56, A:A57, A:E58, A:E59, A:Q60, A:S61, A:E62, A:F63 | 37 | 0.701 |
5 | A:D64, A:V65, A:I66, A:L67, A:E68, A:A69, A:A70, A:G71, A:D72, A:K73, A:K74, A:I75, 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:K119, A:L120, A:E121, A:A122, A:A123, A:G124, A:A125, A:T126, A:V127, A:T128, A:V129, A:K130, A:E131, A:A132, A:A133, A:A134, A:K135, A:N136, A:P137, A:R138, A:E139, A:T140, A:G232, A:P233, A:G234, A:P235, A:G236, A:R271, A:G272, A:P273, A:G274, A:P275, A:G276, A:K277, A:H278, A:R279, A:P295, A:G296 | 67 | 0.691 |
6 | A:K344, A:V398, A:T400, A:L401, A:Q402, A:V403, A:D404, A:G405, A:K406, A:K407, A:L408, A:M409, A:G410, A:S411, A:S412, A:P413, A:Y414, A:Q415, A:R416, A:H417, A:R418 | 21 | 0.624 |
7 | A:L4, A:S5, A:T6, A:D7, A:E8, A:L10 | 6 | 0.622 |
8 | A:A371, A:G372, A:P373, A:G374, A:P375, A:G376, A:G377, A:S378, A:A379, A:A380, A:P381, A:A382, A:A383, A:K392 | 14 | 0.53 |
Features | MERV-MHCI | MERV-MHCII | MERV-TLR4 |
---|---|---|---|
HADDOCK Score | 217.3 ± 14.2 | 179.4 ±27.3 | 213.6 ± 14.6 |
Cluster Size | 5 | 3 | 7 |
Van der Waals energy | −40.8 ± 3.9 | −71.1 ± 2.25 | −41.7 ± 1.3 |
Desolvation energy | −1.41 ± 0.7 | −10.7 ± 4.81 | −0.57 ± 3.35 |
Electrostatic energy | −61.8 ± 9.5 | −267.1 ± 24.8 | −65.1 ± 23.8 |
RMSD from the overall lowest energy structure | 35.6 ± 0.3 | 10.3 ± 0.5 | 50.4 ± 0.1 |
Buried surface area | 2211.9 ± 100.2 | 2871.6 ± 60.1 | 2171.9 ± 121.9 |
Z-Score | −1.2 | −0.9 | −1.7 |
Restraint violation energy | 2246.2 ± 162.9 | 3724.6 ± 152.4 | 2920.9 ± 179.4 |
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Islam, S.I.; Sanjida, S.; Ahmed, S.S.; Almehmadi, M.; Allahyani, M.; Aljuaid, A.; Alsaiari, A.A.; Halawi, M. Core Proteomics and Immunoinformatic Approaches to Design a Multiepitope Reverse Vaccine Candidate against Chagas Disease. Vaccines 2022, 10, 1669. https://doi.org/10.3390/vaccines10101669
Islam SI, Sanjida S, Ahmed SS, Almehmadi M, Allahyani M, Aljuaid A, Alsaiari AA, Halawi M. Core Proteomics and Immunoinformatic Approaches to Design a Multiepitope Reverse Vaccine Candidate against Chagas Disease. Vaccines. 2022; 10(10):1669. https://doi.org/10.3390/vaccines10101669
Chicago/Turabian StyleIslam, Sk Injamamul, Saloa Sanjida, Sheikh Sunzid Ahmed, Mazen Almehmadi, Mamdouh Allahyani, Abdulelah Aljuaid, Ahad Amer Alsaiari, and Mustafa Halawi. 2022. "Core Proteomics and Immunoinformatic Approaches to Design a Multiepitope Reverse Vaccine Candidate against Chagas Disease" Vaccines 10, no. 10: 1669. https://doi.org/10.3390/vaccines10101669
APA StyleIslam, S. I., Sanjida, S., Ahmed, S. S., Almehmadi, M., Allahyani, M., Aljuaid, A., Alsaiari, A. A., & Halawi, M. (2022). Core Proteomics and Immunoinformatic Approaches to Design a Multiepitope Reverse Vaccine Candidate against Chagas Disease. Vaccines, 10(10), 1669. https://doi.org/10.3390/vaccines10101669