Beta Spike-Presenting SARS-CoV-2 Virus-like Particle Vaccine Confers Broad Protection against Other VOCs in Mice
Abstract
1. Introduction
2. Materials and Methods
2.1. Ethics Statement
2.2. Cell and Viruses
2.3. Mouse Experiments
2.4. Generation of SMEN VLPs
2.5. Western Blot
2.6. SMEN VLPs Vaccination Regimen and SARS-CoV-2 Challenge
2.7. Passive Transfer of Sera
2.8. Immunodepletion of CD4+ and CD8+ T Cells
2.9. Bioluminescence Imaging (BLI) of SARS-CoV-2 Infection
2.10. SARS-CoV-2 Neutralization Assay and Calculation of Cross-Reactive Neutralization Index
2.11. Fc-Signaling Assay and Calculation of Cross-Reactive Fc-Signaling Index
2.12. Plaque Forming Assay
2.13. Measurement of Viral Burden
2.14. mRNA Expression Analyses of Signature Inflammatory Cytokines and Lung Injury/Repair Genes
2.15. Disease Burden and Bliss Index Scores
2.16. Cryo-Electron Tomography of SARS-CoV-2 VLPs
2.17. Quantification and Statistical Analysis
3. Results
3.1. Systemic and Mucosal Vaccination of the SARS-CoV-2 VLPs (SMEN) Vaccine Provides Enhanced Protection in K18-hACE2 Mice against a Lethal Virus Challenge
3.2. Antibodies Play a Major Role in SMEN Vaccine-Mediated Protection
3.3. CD8+ and CD4+ T Cells Elicited by SMEN Vaccine Play a Minor but Distinct Role in Immunity by Contributing to Diminishing Virus Spread and Reducing Inflammation
3.4. Cross-Protective Efficacy of SMENWA1 Vaccine Is Reduced against Delta and Ineffective against Beta VOC
3.5. SMENOmicron Vaccine Provides Diminished Cross-Protection against Previous Variants of SARS-CoV-2
3.6. SMENBeta Vaccine Provides Broad Cross-Protection against Heterologous Variants of SARS-CoV-2
SMEN Vaccine | Homologous/Cross-Neutralization (Mean IC50; µL of Serum) | Mortality | Disease Burden | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
WA1 | Delta | Beta | Omicron | WA1 | Delta | Beta | WA1 | Delta | Beta | Omicron * | |
Vehicle | - | - | - | - | 100% Death 6 dpi | 100% Death 6–7 dpi | 100% Death 6 dpi | 100 | 100 | 100 | 100 * |
SMENWA1 (i.m.) | 0.16 | - | - | - | 0% | - | - | 4.59 | - | - | - |
SMENWA1 (i.n.) | 1.30 | - | - | - | 0% | - | - | 1.24 | - | - | - |
SMENWA1 (i.m. + i.n.) | 0.05 | 0.79 | 3.91 | 3.51 | 0% | 25% Delayed Death 8 dpi | 100% Delayed Death 7–8 dpi | 0.41 | 9.50 | 48.8 | - |
SMENOmicron (i.m. + i.n.) | 2.20 | 6.09 | 3.14 | 0.40 | 50% Delayed Death 9–11 dpi | 100% Delayed Death 8–9 dpi | 75% Delayed Death 6–10 dpi | 15.61 | 44.16 | 39.20 | 9.37 * |
SMENBeta (i.m. + i.n.) | 0.42 | 1.83 | 0.22 | 0.32 | 0% | 0% | 0% | 1.08 | 3.79 | 0.91 | 20.54 * |
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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Ullah, I.; Symmes, K.; Keita, K.; Zhu, L.; Grunst, M.W.; Li, W.; Mothes, W.; Kumar, P.; Uchil, P.D. Beta Spike-Presenting SARS-CoV-2 Virus-like Particle Vaccine Confers Broad Protection against Other VOCs in Mice. Vaccines 2024, 12, 1007. https://doi.org/10.3390/vaccines12091007
Ullah I, Symmes K, Keita K, Zhu L, Grunst MW, Li W, Mothes W, Kumar P, Uchil PD. Beta Spike-Presenting SARS-CoV-2 Virus-like Particle Vaccine Confers Broad Protection against Other VOCs in Mice. Vaccines. 2024; 12(9):1007. https://doi.org/10.3390/vaccines12091007
Chicago/Turabian StyleUllah, Irfan, Kelly Symmes, Kadiatou Keita, Li Zhu, Michael W. Grunst, Wenwei Li, Walther Mothes, Priti Kumar, and Pradeep D. Uchil. 2024. "Beta Spike-Presenting SARS-CoV-2 Virus-like Particle Vaccine Confers Broad Protection against Other VOCs in Mice" Vaccines 12, no. 9: 1007. https://doi.org/10.3390/vaccines12091007
APA StyleUllah, I., Symmes, K., Keita, K., Zhu, L., Grunst, M. W., Li, W., Mothes, W., Kumar, P., & Uchil, P. D. (2024). Beta Spike-Presenting SARS-CoV-2 Virus-like Particle Vaccine Confers Broad Protection against Other VOCs in Mice. Vaccines, 12(9), 1007. https://doi.org/10.3390/vaccines12091007