Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design
Abstract
:1. Introduction
2. Results
2.1. Computational Analysis of Immunological Characteristics
2.2. Ex Vivo Validation of the Immune Response
2.2.1. Optimization of Neoantigen Selection for Vaccine Design
- Peptide 1: DWLEWLRQLSLELLKFRDQSLSYHHTMVVQIGRFANYFRNLLPSN
- Peptide 2: MRHSFFSEVNWQDVYRLFMHHVFLEPITCVCSRRFYQFTKLLDSV
2.2.2. Optimization of Neoantigen Selection for Vaccine Design
3. Discussion
4. Materials and Methods
4.1. Computational Testing
4.1.1. Sample Acquisition for in Silico Assays
4.1.2. Detection of Genome Mutations
4.1.3. Determination of Potential Neoantigens and the Main Characteristics
4.1.4. Statistics
4.2. Experimental Testing
4.2.1. Sample Acquisition for Ex Vivo Assays
4.2.2. Estimation of Neoantigens’ Characteristics with Bioinformatic Tools
4.2.3. Optimization and Selection of Neoantigens
4.2.4. Peptide Synthesis
- DWLEWLRQLSLELLKFRDQSLSYHHTMVVQIGRFANYFRNLLPSN
- MRHSFFSEVNWQDVYRLFMHHVFLEPITCVCSRRFYQFTKLLDSV
- PSLQVITFKQRPRKLSHIRPYMNEIVTLMRFLPQVMPMFLNVIRV
- LKCVQFLSQVMPTFLIHCFENVISIMFLVAAGATLERAKTLSPGK
4.2.5. Preparation of PEI-Coated PLGA Nanoparticles (NPs)
4.2.6. Characterization of PEI-Coated PLGA NPs
4.2.7. Generation of Monocyte-Derived Dendritic Cells (DCs)
4.2.8. Dendritic Cell Maturation
4.2.9. DC/T Cell Co-Cultures
4.2.10. Flow Cytometry Analysis
4.2.11. ELISA from Supernatants
4.2.12. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ACN | Acetonitrile |
Ag | Antigen |
APC | Antigen-Presenting Cell |
CI | Confidence interval |
DC | Dendritic cell |
DCM | Dichloromethane |
EE | Encapsulation efficacy |
GRAVY | Grand average of hydropathicity index |
HAS | Human serum |
HLA | Human Leucocytic Antigen |
IEDB | Immune epitope database |
IFN | Interferon |
IL | Interleukin |
MHC | Major Histocompatibility Complex |
NP | Nanoparticle |
PBL | Peripheral blood lymphocyte |
PBMC | Peripheral blood mononuclear cells |
PdI | Polydispersity index |
PEI | Polyethylenimine |
PLGA | Polyethylenimine-coated L-lactic-co-glycolic acid |
SAP | Surface Absorbed Protein |
SD | Standard deviation |
TAP | Transporter associated with antigen processing |
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HLA-I | 1st Patient | 2nd Patient | 3rd Patient | 4th Patient | 5th Patient | 6th Patient | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
1st | 2nd | 1st | 2nd | 1st | 2nd | 1st | 2nd | 1st | 2nd | 1st | 2nd | |
A | 01:01:01 | 02:01:01 | 02:01:01 | 32:01:01 | 24:02:01 | 32:01:01 | 02:01:01 | 11:01:01 | 24:02:01 | 24:02:01 | 03:01:01 | 26:01:01 |
B | 08:01:01 | 44:27:01 | 35:11:01 | 51:01:01 | 07:02:01 | 51:01:01 | 27:05:02 | 40:01:02 | 35:01:01 | 40:01:03 | 07:02:01 | 18:01:01 |
C | 07:01:01 | 07:04:01 | 02:02:02 | 04:01:01 | 07:02:01 | 15:02:01 | 01:02:01 | 03:04:01 | 03:04:01 | 04:01:01 | 02:02:02 | 07:02:01 |
HLA-II | 1st Patient | 2nd Patient | 3rd Patient | 4th Patient | 5th Patient | 6th Patient | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
1st | 2nd | 1st | 2nd | 1st | 2nd | 1st | 2nd | 1st | 2nd | 1st | 2nd | |
DPA1 | 01:03:01 | 02:01:01 | 01:03:01 | 01:03:01 | 01:03:01 | 01:03:01 | 01:03:01 | 01:03:01 | 01:03:01 | 01:03:01 | 01:03:01 | 02:01:01 |
DPB1 | 02:01:02 | 14:01:01 | 02:01:02 | 04:01:01 | --:01:-- | --:01:-- | 04:01:01 | 06:01:-- | 04:01:01 | 04:01:01 | 02:01:02 | 11:01:01 |
DQA1 | 01:02:02 | 01:04:01 | 01:02:01 | 05:05:01 | 01:02:01 | 01:03:01 | 03:01:01 | 04:01:01 | 01:01:01 | 04:01:01 | 01:03:01 | 05:05:01 |
DQB1 | 05:02:01 | 05:03:01 | 03:01:01 | 06:02:01 | 06:02:01 | 06:03:01 | 03:02:01 | 04:02:01 | 04:02:01 | 05:01:01 | 03:01:01 | 06:03:01 |
DRB1 | 16:01:01 | 14:54:01 | 15:01:01 | 11:04:01 | 15:01:01 | 13:01:01 | 08:01:-- | 04:04:01 | 01:01:01 | 08:02:01 | --:--:-- | --:--:-- |
DRB3 | 02:02:01 | --:--:-- | 02:02:01 | --:--:-- | 01:01:02 | --:--:-- | --:--:-- | --:--:-- | --:--:-- | --:--:-- | 01:01:02 | 01:01:02 |
DRB4 | --:--:-- | --:--:-- | --:--:-- | --:--:-- | --:--:-- | --:--:-- | 01:03:01 | 01:03:01 | --:--:-- | --:--:-- | --:--:-- | --:--:-- |
DRB5 | 02:02:-- | --:--:-- | 01:01:01 | --:--:-- | 01:01:01 | --:--:-- | --:--:-- | --:--:-- | --:--:-- | --:--:- | --:--:-- | --:--:-- |
Neoantigen | Immunogenicity | HLA-I | HLA-II | Hydrophilicity | TAP, Proteosome | VaxiJen | Variant Frequency |
---|---|---|---|---|---|---|---|
DWLEWLRQLSLELLK | 0.556 | 0.875 | 1 | 0.366 | 0.722 | 0.516 | 0.199 |
FRDQSLSYHHTMVVQ | 0.335 | 1 | 0 | 0.501 | 0.558 | 0.453 | 0.304 |
IGRFANYFRNLLPSN | 0.851 | 0.665 | 0.529 | 0.41 | 0.567 | 0.555 | 0.333 |
MRHSFFSEVNWQDVY | 0.878 | 0 | 0.452 | 0.535 | 0.72 | 0.427 | 0.339 |
RLFMHHVFLEPITCV | 1 | 0.366 | 0.432 | 0 | 0.603 | 0 | 0.762 |
CSRRFYQFTKLLDSV | 0.518 | 0.562 | 0.788 | 0.398 | 0.608 | 0.379 | 0.466 |
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Malaina, I.; Gonzalez-Melero, L.; Martínez, L.; Salvador, A.; Sanchez-Diez, A.; Asumendi, A.; Margareto, J.; Carrasco-Pujante, J.; Legarreta, L.; García, M.A.; et al. Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design. Int. J. Mol. Sci. 2023, 24, 9024. https://doi.org/10.3390/ijms24109024
Malaina I, Gonzalez-Melero L, Martínez L, Salvador A, Sanchez-Diez A, Asumendi A, Margareto J, Carrasco-Pujante J, Legarreta L, García MA, et al. Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design. International Journal of Molecular Sciences. 2023; 24(10):9024. https://doi.org/10.3390/ijms24109024
Chicago/Turabian StyleMalaina, Iker, Lorena Gonzalez-Melero, Luis Martínez, Aiala Salvador, Ana Sanchez-Diez, Aintzane Asumendi, Javier Margareto, Jose Carrasco-Pujante, Leire Legarreta, María Asunción García, and et al. 2023. "Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design" International Journal of Molecular Sciences 24, no. 10: 9024. https://doi.org/10.3390/ijms24109024