Molecular Design of Encapsulin Protein Nanoparticles to Display Rotavirus Antigens for Enhancing Immunogenicity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plasmid DNA (pDNA)
2.2. Production and Purification of Recombinant Protein pDNAs
2.3. Production of ENC-Based Nanoparticles (NPs)
2.3.1. Cell Lysis and Initial Preparation
2.3.2. Purification of ENC-Based NPs
2.3.3. Final Purification and Quality Control
2.4. Characterization of ENC-Based NPs with TEM
2.5. DLS Analysis of ENC-Based NPs
2.6. Mouse Immunizations with ENC-Based NPs
2.7. Detection of Binding Antibodies by Enzyme-Linked Immunosorbent Assay
2.8. Measurement of Neutralization Activity in Serum against Rotavirus
2.9. Statistical Analyses
3. Results
3.1. Construction of Expression Vectors for the Soluble Expression of ENC Rotavirus VP8* Fusion Protein in E. coli
3.2. Enhanced Efficiency of TEV Cleavage and Assembly of ENC-VP8* via the Introduction of (GS)3 Linker
3.3. Role of L2 in Enhancing Solubility and High-Yield Expression of ENC-VP8* NPs
3.4. Simple Two-Step Purification Process Enables the Production of ENC-VP8* NPs in a Stable and Efficient Manner
3.5. Preparation of ENC-P2-VP8* and P2-VP8* for the Comparison Study
3.6. NP-Based ENC-P2-VP8* Enhances Binding and Neutralizing Antibody Responses Compared to the Subunit P2-VP8* in Mice
4. Discussion
5. Conclusions
6. Patents
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Antigen | Dose | ENC-P2-VP8* Mid | ENC-P2-VP8* Low | P2-VP8* High | P2-VP8* Mid | P2-VP8* Low |
---|---|---|---|---|---|---|
ENC-P2-VP8* high | 1st | ns (p = 0.6905) | ** (p = 0.0079) | ** (p = 0.0079) | ** (p = 0.0079) | ** (p = 0.0079) |
2nd | ns (p = 0.4206) | * (p = 0.0317) | ** (p = 0.0079) | ** (p = 0.0079) | ** (p = 0.0079) | |
3rd | ns (p = 0.4206) | ns (p = 0.2222) | * (p = 0.0159) | * (p = 0.0159) | ** (p = 0.0079) | |
ENC-P2-VP8* mid | 1st | - | * (p = 0.0476) | ns (p = 0.1032) | * (p = 0.0476) | * (p = 0.0476) |
2nd | - | * (p = 0.0159) | ** (p = 0.0079) | ** (p = 0.0079) | ** (p = 0.0079) | |
3rd | - | ns (p = 0.0952) | ** (p = 0.0079) | ** (p = 0.0079) | ** (p = 0.0079) | |
ENC-P2-VP8* low | 1st | - | - | ns (p = 0.4444) | ns (p > 0.9999) | ns (p > 0.9999) |
2nd | - | - | * (p = 0.0159) | * (p = 0.0159) | ** (p = 0.0079) | |
3rd | - | - | ns (p = 0.0556) | ns (p = 0.0556) | ** (p = 0.0079) | |
P2-VP8* high | 1st | - | - | - | ns (p = 0.4444) | ns (p = 0.4444) |
2nd | - | - | - | ns (p = 0.1508) | ** (p = 0.0079) | |
3rd | - | - | - | ns (p = 0.2222) | ** (p = 0.0079) | |
P2-VP8* mid | 1st | - | - | - | - | ns (p > 0.9999) |
2nd | - | - | - | - | ** (p = 0.0079) | |
3rd | - | - | - | - | ** (p = 0.0079) |
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Jung, H.-G.; Jeong, S.; Kang, M.-J.; Hong, I.; Park, Y.-S.; Ko, E.; Kim, J.-O.; Choi, D.-Y. Molecular Design of Encapsulin Protein Nanoparticles to Display Rotavirus Antigens for Enhancing Immunogenicity. Vaccines 2024, 12, 1020. https://doi.org/10.3390/vaccines12091020
Jung H-G, Jeong S, Kang M-J, Hong I, Park Y-S, Ko E, Kim J-O, Choi D-Y. Molecular Design of Encapsulin Protein Nanoparticles to Display Rotavirus Antigens for Enhancing Immunogenicity. Vaccines. 2024; 12(9):1020. https://doi.org/10.3390/vaccines12091020
Chicago/Turabian StyleJung, Hyun-Gyo, Seonghun Jeong, Min-Ji Kang, Ingi Hong, Young-Shin Park, Eunbyeol Ko, Jae-Ouk Kim, and Deog-Young Choi. 2024. "Molecular Design of Encapsulin Protein Nanoparticles to Display Rotavirus Antigens for Enhancing Immunogenicity" Vaccines 12, no. 9: 1020. https://doi.org/10.3390/vaccines12091020
APA StyleJung, H.-G., Jeong, S., Kang, M.-J., Hong, I., Park, Y.-S., Ko, E., Kim, J.-O., & Choi, D.-Y. (2024). Molecular Design of Encapsulin Protein Nanoparticles to Display Rotavirus Antigens for Enhancing Immunogenicity. Vaccines, 12(9), 1020. https://doi.org/10.3390/vaccines12091020