B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2
Abstract
:1. Introduction
2. Materials and Methods
2.1. Design of Chimeric CoV2-TMEP Polyvalent Multiepitopic Immunogen Targeting T Cells
2.2. In Silico Characterization of CoV2-TMEP Synthetic Protein
2.3. Design and In Silico Characterization of the Bi-Cistronic CoV2-BMEP-P2A-TMEP Synthetic Protein
2.4. Cells
2.5. Viruses
2.6. DNA Vectors
2.7. Construction and In Vitro Characterization of MVA-CoV2-B2AT Recombinant Virus
2.8. Expression Analysis of CoV2-TMEP and CoV2-BMEP-P2A-TMEP Multiepitopic Proteins by Western Blotting
2.9. Subcellular Localization of CoV2-TMEP and CoV2-BMEP-P2A-TMEP Multiepitopic Proteins by Immunofluorescence Microscopy
2.10. Peptides
2.11. Ethics Statement
2.12. Preclinical Evaluation of CoV2-TMEP and CoV2-BMEP-P2A-TMEP Proteins in Mice
2.12.1. Analysis of the Impact of CoV2-TMEP or CoV2-BMEP-P2A-TMEP Expression on Immune Cell Recruitment by Flow Cytometry
2.12.2. SARS-CoV-2-Specific Immunogenicity Elicited by CoV2-TMEP or CoV2-BMEP-P2A-TMEP Proteins
2.12.3. Efficacy of MVA-CoV2-B2AT against SARS-CoV-2 Infection in Susceptible K18-hACE2 Tg Mice
SARS-CoV-2 Neutralization Assay
Analysis of SARS-CoV-2 RNA by Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR)
Analysis of SARS-CoV-2 Virus Yields by Plaque Assay
2.13. Data Analysis and Statistics
3. Results
3.1. In Vitro Characterization of the Multiepitopic CoV2-TMEP Protein Expressed from a DNA Vector
3.2. CoV2-TMEP Expression from a DNA Vector Enhances Immune Cell Recruitment in Muscle and DLNs
3.3. Homologous DNA-CoV2-TMEP Prime/Boost Vaccination Regimen Elicits Robust and Polyfunctional SARS-CoV-2-Specific T Cell Responses in C57BL/6 Mice
3.4. In Vitro Characterization of an MVA-Based Vector Expressing the Bi-Cistronic CoV2-BMEP-P2A-TMEP Multiepitopic Protein
3.5. Effect of CoV2-BMEP-P2A-TMEP Expression from an MVA Vector on Immune Cell Recruitment in Muscle and DLNs
3.6. Homologous MVA-CoV2-B2AT Prime/Boost Vaccination Regimen Effectively Induces Neutralizing Antibodies and Reduces SARS-CoV-2 Beta Variant Replication in K18-hACE2 Tg Mice
3.6.1. Analysis of the SARS-CoV-2-Specific Humoral Response at Pre-Challenge
3.6.2. Restricted SARS-CoV-2 Virus Replication Induced by Vaccination
3.7. MVA-CoV2-B2AT Combined with ISG15 Adjuvant Enhanced Magnitude, Breadth and Polyfunctional Profile of the SARS-CoV-2-Specific T Cell Response in C57BL/6 Mice
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Peptide Sequence | Viral Protein | Start | End |
---|---|---|---|
EAEVQIDRLITGRLQSLQTYV | S | 988 | 1008 |
SFPQSAPHGVVFLHVTYVPAQEKN | S | 1051 | 1074 |
WFVTQRNFYEPQIIT | S | 1102 | 1116 |
IVNSVLLFLAFVVFLLV | E | 13 | 29 |
RLCAYCCNIVNVSLVKPSFYVY | E | 38 | 59 |
LQFAYANRNRFLYIIK | M | 35 | 50 |
GTILTRPLLESELVIGAVILRGHLRIAGHHLG | M | 126 | 157 |
SGFAAYSRYRIGNYKL | M | 191 | 206 |
KDLSPRWYFYYLGTGPEAGLPYG | N | 102 | 124 |
ALALLLLDRLNQLESK | N | 218 | 233 |
TKAYNVTQAFGRRGP | N | 265 | 279 |
LTYTGAIKLDDKDPNFKDQVILLNKHIDAYKTFPPTEPKK | N | 331 | 370 |
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Perdiguero, B.; Álvarez, E.; Marcos-Villar, L.; Sin, L.; López-Bravo, M.; Valverde, J.R.; Sorzano, C.Ó.S.; Falqui, M.; Coloma, R.; Esteban, M.; et al. B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2. Vaccines 2024, 12, 1213. https://doi.org/10.3390/vaccines12111213
Perdiguero B, Álvarez E, Marcos-Villar L, Sin L, López-Bravo M, Valverde JR, Sorzano CÓS, Falqui M, Coloma R, Esteban M, et al. B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2. Vaccines. 2024; 12(11):1213. https://doi.org/10.3390/vaccines12111213
Chicago/Turabian StylePerdiguero, Beatriz, Enrique Álvarez, Laura Marcos-Villar, Laura Sin, María López-Bravo, José Ramón Valverde, Carlos Óscar S. Sorzano, Michela Falqui, Rocío Coloma, Mariano Esteban, and et al. 2024. "B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2" Vaccines 12, no. 11: 1213. https://doi.org/10.3390/vaccines12111213