SARS-CoV-2 mRNA vaccine candidate encoding RBD chimera of Delta and Omicron variants: immunogenic potential and validation
-
Shahla Shahsavandi
,
Sina Soleimani
,
Majid Tebyanian
,
Amir Ali Hariri
,
Ashraf Mohammadi
,
Abbas Zare Mirakabadi
,
Mojtaba Noofeli
,
Zarrin Sharifnia
,
Mohammad Mahdi Ranjbar
Abstract
Background and Objectives: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has presented a challenging issue for global health in the 21st century. Frequent mutations in viral genomes have diminished the effectiveness of current vaccines against new variants. Messenger RNA (mRNA) vaccine is a promising platform for eliciting a robust T cell immune response.
Materials and Methods: We evaluated the uptake of mRNA-LNPs into human monocyte-derived dendritic cells by measuring the intensity of enhanced eGFP expression in the transfected cells. Next, we assessed the effect of mRNA-LNPs on immune response induction in mice following a prime-boost immunization strategy, along with analyzing cytokine release. The safety of the vaccine candidate was examined through pyrogenicity and toxicity assays.
Results: Upon intramuscular injection of mice, potent antibodies specific to viral S protein, robust Th1-biased cell-mediated immunity, and enhanced IFN-γ expression were induced. These observations indicate that mRNA-LNP was taken up and that it migrated to the lymph nodes. Furthermore, the vaccine candidate did not cause inflammation or local reactions after injection, as confirmed by biochemical, hematological, and histopathological examinations.
Conclusion: Because of its ability to target immune cells, the mRNA vaccine candidate can potentially improve immune responses against circulating or emerging variants.
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29. Zhang L, Cui Z, Li Q, Wang B, Yu Y, Wu J, et al. Ten emerging SARS-CoV-2 spike variants exhibit variable infectivity, animal tropism, and antibody neutralization. Commun Biol 2021; 4: 1196.
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31. Liu L, Wang P, Nair MS, Yu J, Rapp M, Wang Q, et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature 2020; 584: 450-456.
32. Prabakaran P, Gan J, Feng Y, Zhu Z, Choudhry V, Xiao X, et al. Structure of severe acute respiratory syndrome coronavirus receptor-binding domain complexed with neutralizing antibody. J Biol Chem 2006; 281: 15829-15836.
33. Scheaffer SM, Lee D, Whitener B, Ying B, Wu K, Liang CY, et al. Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA. 5 Omicron variant in mice. Nat Med 2023; 29: 247-257.
34. Zhang Y, Kang X, Liu S, Han P, Lei W, Xu K, et al. Broad protective RBD heterotrimer vaccines neutralize SARS-CoV-2 including Omicron sub-variants XBB/BQ. 1.1/BF. 7. PLoS Pathog 2023; 19(9): e1011659.
35. Eygeris Y, Gupta M, Kim J, Sahay G. Chemistry of lipid nanoparticles for RNA delivery. Acc Chem Res 2022; 55: 2-12.
36. Ramachandran S, Satapathy SR, Dutta T. Delivery strategies for mRNA vaccines. Pharmaceut Med 2022; 36: 11-20.
2. Dong Y, Dai T, Wei Y, Zhang L, Zheng M, Zhou F. A systematic review of SARS-CoV-2 vaccine candidates. Signal Transduct Target Ther 2020; 5: 237.
3. Krammer F. SARS-CoV-2 vaccines in development. Nature 2020; 586: 516-527.
4. Corbett KS, Edwards DK, Leist SR, Abiona OM, Boyoglu-Barnum S, Gillespie RA, et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature 2020; 586: 567-571.
5. Jia L, Qian SB. Therapeutic mRNA engineering from head to tail. Acc Chem Res 2021; 54: 4272-4282.
6. Presnyak V, Alhusaini N, Chen YH, Martin S, Morris N, Kline N, et al. Codon optimality is a major determinant of mRNA stability. Cell 2015; 160: 1111-1124.
7. Hanson G, Coller J. Codon optimality, bias and usage in translation and mRNA decay. Nat Rev Mol Cell Biol 2018; 19: 20-30.
8. Loughrey D, Dahlman JE. Non-liver mRNA delivery. Acc Chem Res 2022; 55: 13-23.
9. Wadhwa A, Aljabbari A, Lokras A, Foged C, Thakur A. Opportunities and challenges in the delivery of mRNA-based vaccines. Pharmaceutics 2020; 12: 102.
10. Lee Y, Jeong M, Park J, Jung H, Lee H. Immunogenicity of lipid nanoparticles and its impact on the efficacy of mRNA vaccines and therapeutics. Exp Mol Med 2023; 55: 2085-2096.
11. Shi J, Huang M-W, Lu Z-D, Du X-J, Shen S, Xu C-F, et al. Delivery of mRNA for regulating functions of immune cells. J Control Release 2022; 345: 494-511.
12. Tenchov R, Bird R, Curtze AE, Zhou Q. Lipid nanoparticles─ from liposomes to mRNA vaccine delivery, a landscape of research diversity and advancement. ACS Nano 2021; 15: 16982-17015.
13. Shahsavandi S, Hariri AA. SARS-CoV-2 Variant-Specific mRNA vaccine: Pros and cons. Viral Immunol 2023; 36: 186-202.
14. Shahsavandi S, Nasr Isfahani H, Hariri AA, Sharifnia Z, Soleimani S, Moradi A. Safflower-derived cationic lipid nanoparticles: potential impact on the delivery of SARS-CoV-2 mRNA transcripts. Arch Razi Inst 2024; 79: 1217-1226.
15. Clemente-Suárez VJ, Hormeño-Holgado A, Jiménez M, Benitez-Agudelo JC, Navarro-Jiménez E, Perez-Palencia N, et al. Dynamics of population immunity due to the herd effect in the COVID-19 pandemic. Vaccines (Basel) 2020; 8: 236.
16. Frederiksen LSF, Zhang Y, Foged C, Thakur A. The long road toward COVID-19 herd immunity: vaccine platform technologies and mass immunization strategies. Front Immunol 2020; 11: 1817.
17. Li J, Liu Q, Liu J, Fang Z, Luo L, Li S, et al. Development of bivalent mRNA vaccines against SARS-CoV-2 variants. Vaccines (Basel) 2022; 10: 1807.
18. Singh PK, Kulsum U, Rufai SB, Mudliar SR, Singh S. Mutations in SARS-CoV-2 leading to antigenic variations in spike protein: a challenge in vaccine development. J Lab Physicians 2020; 12: 154-160.
19. Antonelli M, Pujol JC, Spector TD, Ourselin S, Steves CJ. Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2. Lancet 2022; 399: 2263-2264.
20. Kumar S, Thambiraja TS, Karuppanan K, Subramaniam G. Omicron and Delta variant of SARS‐CoV‐2: a comparative computational study of spike protein. J Med Virol 2022; 94: 1641-1649.
21. Brandolini M, Gatti G, Grumiro L, Zannoli S, Arfilli V, Cricca M, et al. Omicron sub-lineage BA. 5 and recombinant XBB evasion from antibody neutralisation in BNT162b2 vaccine recipients. Microorganisms 2023; 11: 191.
22. Chakraborty C, Bhattacharya M, Chopra H, Islam MA, Saikumar G, Dhama K. The SARS-CoV-2 Omicron recombinant subvariants XBB, XBB. 1, and XBB. 1.5 are expanding rapidly with unique mutations, antibody evasion, and immune escape properties–an alarming global threat of a surge in COVID-19 cases again? Int J Surg 2023; 109: 1041-1043.
23. Zhang QE, Lindenberger J, Parsons RJ, Thakur B, Parks R, Park CS, et al. SARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition. Mol Cell 2024; 84: 2747-2764. e7.
24. Chavda VP, Bezbaruah R, Deka K, Nongrang L, Kalita T. The Delta and Omicron variants of SARS-CoV-2: what we know so far. Vaccines (Basel) 2022; 10: 1926.
25. Lee IJ, Sun CP, Wu PY, Lan YH, Wang IH, Liu WC, et al. A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants. J Biomed Sci 2022; 29: 49.
26. Li Q, Wu J, Nie J, Zhang L, Hao H, Liu S, et al. The impact of mutations in SARS-CoV-2 spike on viral
infectivity and antigenicity. Cell 2020; 182:1284-1294. e9.
27. Pérez-Then E, Lucas C, Monteiro VS, Miric M, Brache V, Cochon L, et al. Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination. Nat Med 2022; 28: 481-485.
28. Xu W, Wang M, Yu D, Zhang XJ. Variations in SARS-CoV-2 spike protein cell epitopes and glycosylation profiles during global transmission course of COVID-19. Front Immunol 2020; 11: 565278.
29. Zhang L, Cui Z, Li Q, Wang B, Yu Y, Wu J, et al. Ten emerging SARS-CoV-2 spike variants exhibit variable infectivity, animal tropism, and antibody neutralization. Commun Biol 2021; 4: 1196.
30. Amanat F, Thapa M, Lei T, Ahmed SMS, Adelsberg DC, Carreño JM, et al. SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2. Cell 2021; 184: 3936-3948.e10.
31. Liu L, Wang P, Nair MS, Yu J, Rapp M, Wang Q, et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature 2020; 584: 450-456.
32. Prabakaran P, Gan J, Feng Y, Zhu Z, Choudhry V, Xiao X, et al. Structure of severe acute respiratory syndrome coronavirus receptor-binding domain complexed with neutralizing antibody. J Biol Chem 2006; 281: 15829-15836.
33. Scheaffer SM, Lee D, Whitener B, Ying B, Wu K, Liang CY, et al. Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA. 5 Omicron variant in mice. Nat Med 2023; 29: 247-257.
34. Zhang Y, Kang X, Liu S, Han P, Lei W, Xu K, et al. Broad protective RBD heterotrimer vaccines neutralize SARS-CoV-2 including Omicron sub-variants XBB/BQ. 1.1/BF. 7. PLoS Pathog 2023; 19(9): e1011659.
35. Eygeris Y, Gupta M, Kim J, Sahay G. Chemistry of lipid nanoparticles for RNA delivery. Acc Chem Res 2022; 55: 2-12.
36. Ramachandran S, Satapathy SR, Dutta T. Delivery strategies for mRNA vaccines. Pharmaceut Med 2022; 36: 11-20.
| Files | ||
| Issue | Vol 17 No 5 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v17i5.19891 | |
| Keywords | ||
| SARS-CoV-2 mRNA vaccine Receptor binding domain Immunity | ||
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How to Cite
1.
Shahsavandi S, Soleimani S, Tebyanian M, Hariri AA, Mohammadi A, Zare Mirakabadi A, Noofeli M, Sharifnia Z, Ranjbar MM. SARS-CoV-2 mRNA vaccine candidate encoding RBD chimera of Delta and Omicron variants: immunogenic potential and validation. Iran J Microbiol. 2025;17(5):826-834.
