Identifying Key Drivers of Efficient B Cell Responses: On the Role of T Help, Antigen-Organization, and Toll-like Receptor Stimulation for Generating a Neutralizing Anti-Dengue Virus Response
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cloning of “Immune-Tag” nCMV-eGFP, nCMV-PADRE-eGFP, nCMV-PADRE-DV1 Variants
2.2. Protein Production, Purification, and Analysis
2.3. Expression and Purification of CuMV and CuMVTT VLPs
2.4. Isolation and Quantification of RNA from CuMV Samples
2.5. CMV CP mRNA Transcription
2.6. nCMV Binding to Nucleic Acid
2.7. Electrophoretic Nucleic Acid Mobility Shift Assay (Gel Shift)
2.8. Development of CuMV-eGFP and CuMVTT-DV1 Vaccines
2.9. Dynamic Light Scattering Measurement (DLS)
2.10. Sample Analysis by Mass Spectrometry (MS)
2.11. Transmission Electron Microscopy (TEM)
2.12. Mice
2.13. Immunization Regimen
2.14. The Enzyme-Linked Immunosorbent Assay (ELISA)
2.15. DENV-1 Focus Reduction Virus Neutralization Test (FRNT)
2.16. Data Analysis
3. Results
3.1. Development of “IMMUNE-TAG” as a Vaccine Platform
3.2. Chemically Modified VLP-Based Platform
3.3. Characterization of the Immunogenic Potential of nCMV–eGFP Using “Immune-Tag” Technology
3.4. Total Levels of Anti-eGFP IgG
3.5. Subclass-Specific Anti-eGFP IgG Antibodies
3.6. nCMV-PADRE “Immune-Tag” as a Dengue Vaccine Candidate
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
2,5-DHAP | 2,5-dihydroxyacetophenone |
Ab/Abs | antibody/antibodies |
AEC | addition of 3-amino-9-ethylcarbazole |
APCs | antigen-presenting cells |
AI | avidity index |
CMV | cucumber mosaic virus |
CP | capsid or coat protein |
CuMV | cucumber mosaic virus-derived virus-like particles |
CuMVTT | immunologically optimized cucumber mosaic virus-derived VLPs with incorporated universal Th-cell epitope from tetanus toxin |
DENV | dengue virus |
DLS | dynamic light scattering |
DV1 EDIII | third domain of dengue virus 1 envelope protein |
eGFP | enhanced green fluorescent protein |
ELISA | enzyme-linked immunosorbent assay |
FRNT | focus reduction virus neutralization test |
IB | inclusion bodies |
MS | mass spectrometry |
NAGE | native agarose gel electrophoresis |
nCMV | N-terminal fragment of the cucumber mosaic virus capsid protein containing the functional R domain |
ON | overnight |
PADRE | universal synthetic non-natural Pan DR Epitope |
PAMPs | pathogen-associated molecular patterns |
PASPs | Pathogen-associated structural patterns |
PMSF | phenylmethylsulfonyl fluoride |
RT | room temperature |
SATA | N-succinimidyl S-acetylthioacetate |
s.c. | subcutaneous |
SDS-PAGE | sodium dodecyl sulfate-polyacrylamide gel electrophoresis |
SMPH | succinimidyl 6-((β-maleimidopropionamido) hexanoate |
TEM | transmission electron microscopy |
Th | T-cell help |
Th cell | T-helper cell |
TLR | toll-like receptor |
TMB | tetramethylbenzidine |
TT | tetanus toxin |
VLPs | virus-like particles |
WT | wild type |
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Oligonucleotide Name | Sequence |
---|---|
CmN-NcoF | 5′ ATACCATGGACAAATCTGAATCAACCAGT 3′ |
CmN-BamR | 5′ TCTGGATCCCCGGTTGGGTGGTTAATAGTTGGACGA 3′ |
His-tag-C-eGFP-Bsp1407I-F | 5′ AGCTGTACAAGGGTGGCGGATCCCATCATCATCATCATCACCATT 3′ |
His-tag-C-eGFP-SacI-R | 5′ AGCGAGCTCTAGGGCCGCTTTAATGGTGATGATGATGATGATGGG 3′ |
pET-dir | 5′ GGGGAATTGTGAGCGGATAACA 3′ |
pET-rev | 5′ TATTGCTCAGCGGTGGCAGC 3’ |
M13seq-F | 5’ GCCAGGGTTTTCCCAGTCACGA 3’ |
M13seq-R | 5’ GAGCGGATAACAATTTCACACAGG 3’ |
PADRE-eGFP-BamHI-F | 5′ ACCACCCAACCGGGGATCCCGCGAAATTTGTGGCCGCGTGGACCCTC 3’ |
PADRE-eGFP-AgeI-R | 5′ TCACCATGGTGGCCACCGGTGGCGCGGCCGCCTTGAGGGTCCACGCGGCCAC 3’ |
nCMV-Vect_R | 5′ TGCTCGAGAATTCAAGCTTGCTTTACAATAGCGGTGGCGCGGCCGCCT 3′ |
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Sobczak, J.M.; Barkovska, I.; Balke, I.; Rothen, D.A.; Mohsen, M.O.; Skrastina, D.; Ogrina, A.; Martina, B.; Jansons, J.; Bogans, J.; et al. Identifying Key Drivers of Efficient B Cell Responses: On the Role of T Help, Antigen-Organization, and Toll-like Receptor Stimulation for Generating a Neutralizing Anti-Dengue Virus Response. Vaccines 2024, 12, 661. https://doi.org/10.3390/vaccines12060661
Sobczak JM, Barkovska I, Balke I, Rothen DA, Mohsen MO, Skrastina D, Ogrina A, Martina B, Jansons J, Bogans J, et al. Identifying Key Drivers of Efficient B Cell Responses: On the Role of T Help, Antigen-Organization, and Toll-like Receptor Stimulation for Generating a Neutralizing Anti-Dengue Virus Response. Vaccines. 2024; 12(6):661. https://doi.org/10.3390/vaccines12060661
Chicago/Turabian StyleSobczak, Jan M., Irena Barkovska, Ina Balke, Dominik A. Rothen, Mona O. Mohsen, Dace Skrastina, Anete Ogrina, Byron Martina, Juris Jansons, Janis Bogans, and et al. 2024. "Identifying Key Drivers of Efficient B Cell Responses: On the Role of T Help, Antigen-Organization, and Toll-like Receptor Stimulation for Generating a Neutralizing Anti-Dengue Virus Response" Vaccines 12, no. 6: 661. https://doi.org/10.3390/vaccines12060661
APA StyleSobczak, J. M., Barkovska, I., Balke, I., Rothen, D. A., Mohsen, M. O., Skrastina, D., Ogrina, A., Martina, B., Jansons, J., Bogans, J., Vogel, M., Bachmann, M. F., & Zeltins, A. (2024). Identifying Key Drivers of Efficient B Cell Responses: On the Role of T Help, Antigen-Organization, and Toll-like Receptor Stimulation for Generating a Neutralizing Anti-Dengue Virus Response. Vaccines, 12(6), 661. https://doi.org/10.3390/vaccines12060661