A Structural View at Vaccine Development against M. tuberculosis
Abstract
1. Introduction
2. Immune Response to TB Infection
2.1. Innate Immunity against Mtb
2.2. Adaptive Immunity against Mtb
3. Vaccine Approaches against TB
3.1. Live-Attenuated Whole-Cell Vaccines
3.2. Inactivated Whole- and Fragmented-Cell Vaccines
3.3. Viral-Vectored Vaccines
3.4. Protein Subunit Vaccines
3.5. The Contribution of Adjuvants
4. Structural Vaccinology as a Tool to Enhance Antigenicity of TB Subunit Vaccines
Tool | Function | Method | Reference |
---|---|---|---|
VaxiJen v2.0 | Prediction of protective antigens and subunit vaccines | Sequence-based | [100] |
BepiPred 3.0 | Prediction of potential B-cell epitopes | Sequence-based | [101] |
DiscoTope 2.0 IEDB | Prediction of potential B-cell epitopes | Structure-based | [102] |
ElliPro IEDB | B cell epitope prediction, based on solvent-accessibility and flexibility | Structure-based | [103] |
SVMTriP | Prediction of protein regions preferentially recognised by antibodies | Sequence-based | [104] |
Peptide binding to MHC class I molecules IEDB | MHC Class I epitope prediction | Sequence-based | [105] |
Peptide binding to MHC class II molecules IEDB | MHC Class II epitope prediction | Sequence-based | [106] |
NetMHCpan4.1 NetMHCIIpan4.0 | Prediction of CD8 and CD4 T cell epitopes | Sequence-based | [107] |
AllergenFP v.1.0 AllerTop v.2.0 | Allergenicity prediction | Sequence-based | [108,109] |
ToxinPred | Toxicity prediction | Sequence-based | [110] |
Clustal Omega | Multiple sequence alignment using seeded guide trees and HMM profile-profile analysis | Sequence-based | [111] |
5. Novel Promising Subunit Vaccines against TB
5.1. Peptidoglycan Processing Enzymes as Dendritic Cell Stimulators
5.2. Rv2882c and Rv2005c: Combining Dendritic and Macrophage Stimulation
5.3. Rv2299c and ESAT6: Combining Dendritic and T Cell Stimulation
6. Conclusions and Perspectives
Author Contributions
Funding
Conflicts of Interest
Abbreviations
WHO | World Health Organization |
PDB | Protein Data Bank |
TB | Tuberculosis |
Mtb | Mycobacterium tuberculosis |
PAMP | Pathogen Associated Molecular Pattern |
SV | Structural vaccinology |
IFN | Interferon |
AEC | Airway epithelial cell |
NK | Natural killer |
DC | dendritic cell |
TNF | tumor necrosis factor |
TLR | Toll like receptor |
IL | Interleukin |
PMN | polymorphonuclear leukocytes |
MHC | major histocompatibility complex |
ESAT6 | Early Secretory Antigenic Target-6 |
CFP-10 | Culture Filtrate Protein antigen 10-kDa |
CpG | Cytosine phosphate guanosine |
AI | Artificial Intelligence |
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Mtb Protein | Putative Function | Immunogenic Function | Localisation | Structural Information (pdb Code) | Reference |
---|---|---|---|---|---|
Rv2450c (RpfE) | Cell Wall Hydrolase | -DC maturation | periplasm | 4CGE | [119,120] |
Rv1009 (RpfB) | Cell Wall Hydrolase | -DC maturation | periplasm | 4KL7, 4KPM, 4EMN, 3EO5, 5E27 | [121,122,123,124] |
Rv2882c | Ribosome recycling factor | -Macrophage- activator -Boosting BCG | cytoplasm | 4KAW, 4KB2, 4KB4, 4KC6, 4KDD | [125] |
Rv2005c | USP | -DC maturation when fused to Rv2882c | cytoplasm | No structure available | [126] |
Rv3463 | Oxidoreductase | -Macrophage- activator | cytoplasm | No structure available | [127] |
Rv1876 | Bacterioferritin | -DC maturation -Boosting BCG | cytoplasm | 3UOF, 3QB9, 3UOI | [128] |
Rv2299c | Mycobacterial Chaperone | -DC maturation -Boosting BCG fused with ESAT6 | cytoplasm | No structure available | [129,130,131] |
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Romano, M.; Squeglia, F.; Kramarska, E.; Barra, G.; Choi, H.-G.; Kim, H.-J.; Ruggiero, A.; Berisio, R. A Structural View at Vaccine Development against M. tuberculosis. Cells 2023, 12, 317. https://doi.org/10.3390/cells12020317
Romano M, Squeglia F, Kramarska E, Barra G, Choi H-G, Kim H-J, Ruggiero A, Berisio R. A Structural View at Vaccine Development against M. tuberculosis. Cells. 2023; 12(2):317. https://doi.org/10.3390/cells12020317
Chicago/Turabian StyleRomano, Maria, Flavia Squeglia, Eliza Kramarska, Giovanni Barra, Han-Gyu Choi, Hwa-Jung Kim, Alessia Ruggiero, and Rita Berisio. 2023. "A Structural View at Vaccine Development against M. tuberculosis" Cells 12, no. 2: 317. https://doi.org/10.3390/cells12020317
APA StyleRomano, M., Squeglia, F., Kramarska, E., Barra, G., Choi, H.-G., Kim, H.-J., Ruggiero, A., & Berisio, R. (2023). A Structural View at Vaccine Development against M. tuberculosis. Cells, 12(2), 317. https://doi.org/10.3390/cells12020317