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Challenges of Storage and Stability of mRNA-Based COVID-19 Vaccines
Open accessAbstract
In December 2019, a new and highly pathogenic coronavirus emerged—coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), quickly spread throughout the world. In response to this global pandemic, a few vaccines were allowed for emergency use, beginning in November 2020, of which the mRNA-based vaccines by Moderna (Moderna, Cambridge, MA, USA) and BioNTech (BioTech, Mainz, Germany)/Pfizer (Pfizer, New York, NY, USA) have been identified as the most effective ones. The mRNA platform allowed rapid development of vaccines, but their global use is limited by ultracold storage requirements. Most resource-poor countries do not have cold chain storage to execute mass vaccination. Therefore, determining strategies to increase stability of mRNA-based vaccines in relatively higher temperatures can be a game changer to address the current global pandemic and upcoming new waves. In this review, we summarized the current research strategies to enhance stability of the RNA vaccine delivery system.
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In the citing paper
“The degradation of mRNA in the presence of water, attributed to oxidation and hydrolysis43, required mRNA vaccines to be stored and transported at subzero temperatures.”
From An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial (2024) · cites this paper as [43]
Experimental — accuracy not yet measuredIn the citing paper
“For instance, the mRNA-1273 vaccine from Moderna maintains its effectiveness for six months at −20 °C, whereas the effectiveness of the BNT162b2 vaccine from BioNTech is maintained for six months when stored at −60 to −80 °C. Conversely, the CVnCoV vaccine from CureVac can be stored at −60 °C for three months.”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [469]
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“Therefore, existing COVID-19 mRNA vaccines undoubtedly require storage under ultra-low temperatures.469”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [469]
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Cites
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Polack, F. P., Thomas, S. J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Perez, J. L., Pérez Marc, G., Moreira, E. D., Zerbini, C., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2034577 · Cited by 14,592 · cited 4×
“Both Moderna and Pfizer modified the mRNA encoding viral spike protein by replacing natural residues with two consecutive prolines at amino acid positions K986 and V987 for their COVID-19 vaccines [5,6,8].”
BackgroundInfluentialEfficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Baden, L. R., El Sahly, H. M., Essink, B., Kotloff, K., Frey, S., Novak, R., Diemert, D., Spector, S. A., Rouphael, N., Creech, C. B., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2035389 · Cited by 10,119
COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses
Sahin, U., Muik, A., Derhovanessian, E., Vogler, I., Kranz, L. M., Vormehr, M., Baum, A., Pascal, K., Quandt, J., Maurus, D., et al. (2020) · Nature · doi:10.1038/s41586-020-2814-7 · Cited by 1,977
mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability
Schoenmaker, L., Witzigmann, D., Kulkarni, J. A., Verbeke, R., Kersten, G., Jiskoot, W., & Crommelin, D. J. A. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120586 · Cited by 1,566
The Many Pathways of RNA Degradation
Houseley, J. M., & Tollervey, D. W. (2009) · Cell · doi:10.1016/j.cell.2009.01.019 · Cited by 1,220
Lyophilization and development of solid protein pharmaceuticals
Wang, W. (2000) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(00)00423-3 · Cited by 1,178
Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines
Hassett, K. J., Benenato, K. E., Jacquinet, E., Lee, A., Woods, A., Yuzhakov, O., Himansu, S., Deterling, J., Geilich, B. M., Ketova, T., et al. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.01.013 · Cited by 927
A thermostable mRNA vaccine against COVID-19
Zhang, N.-N., Li, X.-F., Deng, Y.-Q., Zhao, H., Huang, Y.-J., Yang, G., Huang, W.-J., Gao, P., Zhou, C., Zhang, R.-R., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.024 · Cited by 671
Gene delivery by lipoplexes and polyplexes
de Ilarduya, C. T., Sun, Y., & Düzgüneş, N. (2010) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2010.03.019 · Cited by 626
Opportunities and Challenges in the Delivery of mRNA-Based Vaccines
Wadhwa, A., Aljabbari, A., Lokras, A., Foged, C., & Thakur, A. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12020102 · Cited by 584
Addressing the Cold Reality of mRNA Vaccine Stability
Crommelin, D. J. A., Anchordoquy, T. J., Volkin, D. B., Jiskoot, W., & Mastrobattista, E. (2021) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2020.12.006 · Cited by 517
Recent advances in siRNA delivery mediated by lipid-based nanoparticles
Yonezawa, S., Koide, H., & Asai, T. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.07.022 · Cited by 394
Three decades of messenger RNA vaccine development
Verbeke, R., Lentacker, I., De Smedt, S. C., & Dewitte, H. (2019) · Nano Today · doi:10.1016/j.nantod.2019.100766 · Cited by 342
Polymer–Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs
Kaczmarek, J. C., Patel, A. K., Kauffman, K. J., Fenton, O. S., Webber, M. J., Heartlein, M. W., DeRosa, F., & Anderson, D. G. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201608450 · Cited by 337
The COVID-19 Vaccine Race: Challenges and Opportunities in Vaccine Formulation
Wang, J., Peng, Y., Xu, H., Cui, Z., & Williams, R. O. (2020) · AAPS PharmSciTech · doi:10.1208/s12249-020-01744-7 · Cited by 335
Ball, R., Bajaj, P., & Whitehead, K. (2016) · International Journal of Nanomedicine · doi:10.2147/ijn.s123062 · Cited by 333 · cited 4×
“The stability of this emerging and fast-growing vaccine platform is poorly understood, and it likely depends on multiple factors, such as excipients, pH, and temperature [12].”
BackgroundInfluentialLipid Nanoparticle Formulations for Enhanced Co-delivery of siRNA and mRNA
Ball, R. L., Hajj, K. A., Vizelman, J., Bajaj, P., & Whitehead, K. A. (2018) · Nano Letters · doi:10.1021/acs.nanolett.8b01101 · Cited by 315
An Update on Self-Amplifying mRNA Vaccine Development
Blakney, A. K., Ip, S., & Geall, A. J. (2021) · Vaccines · doi:10.3390/vaccines9020097 · Cited by 288
Lipid Nanoparticles as Delivery Systems for RNA-Based Vaccines
Aldosari, B. N., Alfagih, I. M., & Almurshedi, A. S. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13020206 · Cited by 248
Long-term storage of lipid-like nanoparticles for mRNA delivery
Zhao, P., Hou, X., Yan, J., Du, S., Xue, Y., Li, W., Xiang, G., & Dong, Y. (2020) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.03.001 · Cited by 233
Tregoning, J. S., Brown, E. S., Cheeseman, H. M., Flight, K. E., Higham, S. L., Lemm, N.-M., Pierce, B. F., Stirling, D. C., Wang, Z., & Pollock, K. M. (2020) · Clinical & Experimental Immunology · doi:10.1111/cei.13517 · Cited by 226
Next-Generation Lipids in RNA Interference Therapeutics
Rietwyk, S., & Peer, D. (2017) · ACS Nano · doi:10.1021/acsnano.7b04734 · Cited by 199
Theoretical basis for stabilizing messenger RNA through secondary structure design
Wayment-Steele, H. K., Kim, D. S., Choe, C. A., Nicol, J. J., Wellington-Oguri, R., Watkins, A. M., Sperberg, R. A. P., Huang, P.-S., Participants, E., & Das, R. (2020) · doi:10.1101/2020.08.22.262931 · Cited by 199
Theoretical basis for stabilizing messenger RNA through secondary structure design
Wayment-Steele, H. K., Kim, D. S., Choe, C. A., Nicol, J. J., Wellington-Oguri, R., Watkins, A. M., Parra Sperberg, R. A., Huang, P.-S., Participants, E., & Das, R. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab764 · Cited by 197
Development of Stable Influenza Vaccine Powder Formulations: Challenges and Possibilities
Amorij, J.-P., Huckriede, A. L. W., Wilschut, J., Frijlink, H. W., & Hinrichs, W. L. J. (2008) · Pharmaceutical Research · doi:10.1007/s11095-008-9559-6 · Cited by 186
Basha, G., Novobrantseva, T. I., Rosin, N. L., Tam, Y. Y. C., Hafez, I. M., Wong, M., Sugo, T., Ruda, V. M., Qin, J., Klebanov, B., et al. (2011) · Molecular Therapy · doi:10.1038/mt.2011.190 · Cited by 182
Degradation of mRNAs that lack a stop codon: a decade of nonstop progress
Klauer, A. A., & van Hoof, A. (2012) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1124 · Cited by 171
Rauch, S., Roth, N., Schwendt, K., Fotin-Mleczek, M., Mueller, S. O., & Petsch, B. (2021) · npj Vaccines · doi:10.1038/s41541-021-00311-w · Cited by 165
Pascolo, S. (2004) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.4.8.1285 · Cited by 152
A thermostable messenger RNA based vaccine against rabies
Stitz, L., Vogel, A., Schnee, M., Voss, D., Rauch, S., Mutzke, T., Ketterer, T., Kramps, T., & Petsch, B. (2017) · PLOS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0006108 · Cited by 117
Long-term storage of DNA-free RNA for use in vaccine studies
Jones, K. L., Drane, D., & Gowans, E. J. (2007) · BioTechniques · doi:10.2144/000112593 · Cited by 115
Binzel, D. W., Li, X., Burns, N., Khan, E., Lee, W.-J., Chen, L.-C., Ellipilli, S., Miles, W. O., Ho, Y. S., & Guo, P. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00009 · Cited by 97
Huang, Q., Zeng, J., & Yan, J. (2021) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2021.02.006 · Cited by 91
Synthetic Messenger RNA-Based Vaccines: From Scorn to Hype
Pascolo, S. (2021) · Viruses · doi:10.3390/v13020270 · Cited by 87
Lipid Polymer Hybrid Nanomaterials for mRNA Delivery
Zhao, W., Zhang, C., Li, B., Zhang, X., Luo, X. L., Zeng, C., Li, W., Gao, M., & Dong, Y. (2018) · Cellular and Molecular Bioengineering · doi:10.1007/s12195-018-0536-9 · Cited by 86
Batty, C. J., Heise, M. T., Bachelder, E. M., & Ainslie, K. M. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.12.006 · Cited by 86
A flexible, thermostable nanostructured lipid carrier platform for RNA vaccine delivery
Gerhardt, A., Voigt, E. A., Archer, M. C., Reed, S., Larson, E., Hoeven, N. V., Kramer, R. M., Fox, C. B., & Casper, C. (2022) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.03.009 · Cited by 86
Viral and Synthetic RNA Vector Technologies and Applications
Schott, J. W., Morgan, M., Galla, M., & Schambach, A. (2016) · Molecular Therapy · doi:10.1038/mt.2016.143 · Cited by 76
RNA Viruses as Tools in Gene Therapy and Vaccine Development
Lundstrom, K. H. (2019) · Genes · doi:10.3390/genes10030189 · Cited by 75
Recent advances in polymeric materials for the delivery of RNA therapeutics
Ulkoski, D., Bak, A., Wilson, J. T., & Krishnamurthy, V. R. (2019) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2019.1663822 · Cited by 74
siRNA-lipid nanoparticles with long-term storage stability facilitate potent gene-silencing in vivo
Suzuki, Y., Hyodo, K., Tanaka, Y., & Ishihara, H. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.10.024 · Cited by 71
Alphavirus vectors for vaccine production and gene therapy
Lundstrom, K. H. (2003) · Expert Review of Vaccines · doi:10.1586/14760584.2.3.445 · Cited by 67
Picornavirus Modification of a Host mRNA Decay Protein
Rozovics, J. M., Chase, A. J., Cathcart, A. L., Chou, W., Gershon, P. D., Palusa, S. G., Wilusz, J., & Semler, B. L. (2012) · mBio · doi:10.1128/mbio.00431-12 · Cited by 61
Polymer–Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs
Kaczmarek, J. C., Patel, A. K., Kauffman, K. J., Fenton, O. S., Webber, M. J., Heartlein, M. W., DeRosa, F., & Anderson, D. G. (2016) · Angewandte Chemie · doi:10.1002/ange.201608450 · Cited by 60
The Science is There: Key Considerations for Stabilizing Viral Vector-Based Covid-19 Vaccines
Crommelin, D. J. A., Volkin, D. B., Hoogendoorn, K. H., Lubiniecki, A. S., & Jiskoot, W. (2020) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2020.11.015 · Cited by 59
Polylactide-Based Reactive Micelles as a Robust Platform for mRNA Delivery
Lacroix, C., Humanes, A., Coiffier, C., Gigmès, D., Verrier, B., & Trimaille, T. (2020) · Pharmaceutical Research · doi:10.1007/s11095-019-2749-6 · Cited by 41
Alphaviruses: Semliki Forest Virus and Sindbis Virus Vectors for Gene Transfer into Neurons
Ehrengruber, M. U., Schlesinger, S., & Lundstrom, K. H. (2011) · Current Protocols in Neuroscience · doi:10.1002/0471142301.ns0422s57 · Cited by 40
What went wrong with CureVac's mRNA vaccine?
Cohen, J. (2021) · Science · doi:10.1126/science.372.6549.1381 · Cited by 25
Wang, C., Siriwardane, D. A., Jiang, W., & Mudalige, T. (2019) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2019.118576 · Cited by 24
COVID-19 vaccines poised for launch, but impact on pandemic unclear
Dolgin, E. (2020) · Nature Biotechnology · doi:10.1038/d41587-020-00022-y · Cited by 24
Hong, H., Kim, K. S., Park, S. A., Chun, M. J., Hong, E. Y., Chung, S. W., Kim, H. J., Shin, B. G., Braka, A., Thanappan, J., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.22.436375 · Cited by 20
Roth, N., Schön, J., Hoffmann, D., Thran, M., Thess, A., Mueller, S. O., Petsch, B., & Rauch, S. (2021) · doi:10.1101/2021.05.13.443734 · Cited by 18
Nanotechnology-Enabled COVID-19 mRNA Vaccines
Gao, Y., Yang, K., Shelling, A. N., & Wu, Z. (2021) · Encyclopedia · doi:10.3390/encyclopedia1030059 · Cited by 18
Gebre, M. S., Rauch, S., Roth, N., Yu, J., Chandrashekar, A., Mercado, N. B., He, X., Liu, J., McMahan, K., Martinot, A., et al. (2021) · doi:10.1101/2021.08.13.456316 · Cited by 8
Research works printed but not linked: 1
- Roth, N., Schoen, J., Hoffmann, D., Thran, M., Thess, A., Mueller, S.O., Petsch, B., and Rauch, S. (2021). CV2CoV, an enhanced mRNA-based SARS-CoV-2 vaccine candidate, supports higher protein expression and improved immunogenicity in rats. bioRxiv.
Cited by
Sorted by citations
Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants
Qu, L., Yi, Z., Shen, Y., Lin, L., Chen, F., Xu, Y., Wu, Z., Tang, H., Zhang, X., Tian, F., et al. (2021) · doi:10.1101/2021.03.16.435594 · Cited by 636
Advances in COVID-19 mRNA vaccine development
Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601
The Storage and In-Use Stability of mRNA Vaccines and Therapeutics: Not A Cold Case
Blenke, E. O., Örnskov, E., Schöneich, C., Nilsson, G. Å., Volkin, D. B., Mastrobattista, E., Almarsson, Ö., & Crommelin, D. J. A. (2022) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2022.11.001 · Cited by 221
Lipid nanoparticles for siRNA delivery in cancer treatment
Moukhtari, S. H. E., Garbayo, E., Amundarain, A., Pascual‐Gil, S., Carrasco‐Leon, A., Prósper, F., Agirre, X., & Blanco‐Prieto, M. J. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.07.054 · Cited by 221
Delivery Strategies for mRNA Vaccines
Ramachandran, S., Satapathy, S. R., & Dutta, T. (2022) · Pharmaceutical Medicine · doi:10.1007/s40290-021-00417-5 · Cited by 191
Metadata
- Authors
- Uddin, M. N., & Roni, M. A.
- Affiliations
- Mercer University (US)
- Peoria campus of the University of Illinois System (US)
- Corresponding author
- Roni, Monzurul A.
- Venue
- Vaccines
- Publisher
- MDPI AG
- Published
- 2021-09-17
- Volume
- 9
- Issue
- 9
- Pages
- 1033
- ISSN
- 2076-393X (ISSN-L)
- PMC
- PMC8473088
- OpenAlex
- W3200035370
- Cited by
- 371
- References
- 54
- Citations by year
- 2026: 50 · 2025: 92 · 2024: 81 · 2023: 80 · 2022: 65 · 2021: 1
- FWCI
- 6.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Vaccines (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- mRNA vaccines, COVID-19 vaccines, SARS-CoV-2, vaccine stability, cold chain storage, storage temperature, vaccine delivery systems, mRNA degradation, resource-poor countries, mass vaccination
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