Melting and Re-Freezing Leads to Irreversible Changes in the Morphology and Molecular-Level Dynamics of Pfizer-BioNTech COVID-19 Vaccine
Open accessAbstract
Background and Objectives: As an mRNA-based vaccine, the Pfizer-BioNTech COVID-19 vaccine has stringent cold storage requirements to preserve functionality of the mRNA active ingredient. To this end, lipid components of the vaccine formulation play an important role in stabilizing and protecting the mRNA molecule for long-term storage. The purpose of the current study was to measure molecular-level dynamics as a function of temperature in the Pfizer-BioNTech COVID-19 vaccine to gain microscopic insight into its thermal stability. Materials and Methods: We used quasielastic and inelastic neutron scattering to probe (1) the vaccine extracted from the manufacturer-supplied vials and (2) unperturbed vaccine in the original manufacturer-supplied vials. The latter measurement was possible due to the high penetrative power of neutrons. Results: Upon warming from the low-temperature frozen state, the vaccine in its original form exhibits two-step melting, indicative of a two-phase morphology. Once the melting is completed (above 0 °C), vaccine re-freezing cannot restore its original two-phase state. This observation is corroborated by the changes in the molecular vibrational spectra. The molecular-level mobility measured in the resulting single-phase state of the re-frozen vaccine greatly exceeds the mobility measured in the original vaccine. Conclusions: Even a brief melting (above 0 °C) leads to an irreversible alteration of the two-phase morphology of the original vaccine formulation. Re-freezing of the vaccine results in a one-phase morphology with much increased molecular-level mobility compared to that in the original vaccine, suggesting irreversible deterioration of the vaccine’s in-storage stability. Neutron scattering can be used to distinguish between the vibrational spectra characteristic of the original and deteriorated vaccines contained in the unperturbed original manufacturer-supplied vials.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Ultra-low temperature preservation is more conducive to maintaining the original conformation of mRNA-LNP complexes.
“In addition, ultra-low temperature preservation is more conducive to maintaining the original conformation of mRNA-LNP complexes.468”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [468]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Lipid nanoparticles for mRNA delivery
Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00358-0 · Cited by 4,076 · see citing works
Mantid—Data analysis and visualization package for neutron scattering and μ SR experiments
Arnold, O., Bilheux, J.-C., Borreguero, J. M., Buts, A., Campbell, S. I., Chapon, L. C., Doucet, M., Draper, N., Leal, R. F., Gigg, M., et al. (2014) · Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment · doi:10.1016/j.nima.2014.07.029 · Cited by 1,812 · see citing works
Azuah, R. T., Kneller, L. R., Qiu, Y., Tregenna‐Piggott, P. L. W., Brown, C. M., Copley, J. R. D., & Dimeo, R. M. (2009) · Journal of Research of the National Institute of Standards and Technology · doi:10.6028/jres.114.025 · Cited by 948 · see citing works
Advances in mRNA Vaccines for Infectious Diseases
Zhang, C., Maruggi, G., Shan, H., & Li, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00594 · Cited by 680 · see citing works
Nanomaterial Delivery Systems for mRNA Vaccines
Buschmann, M. D., Carrasco, M. J., Alishetty, S., Paige, M., Alameh, M. G., & Weissman, D. (2021) · Vaccines · doi:10.3390/vaccines9010065 · Cited by 582 · see citing works
A time-of-flight backscattering spectrometer at the Spallation Neutron Source, BASIS
Mamontov, E., & Herwig, K. W. (2011) · Review of Scientific Instruments · doi:10.1063/1.3626214 · Cited by 355 · see citing works
Self-citationResolution of VISION, a crystal-analyzer spectrometer
Seeger, P. A., Daemen, L. L., & Larese, J. Z. (2009) · Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment · doi:10.1016/j.nima.2009.03.204 · Cited by 103 · see citing works
Self-citationMamontov, E., Luo, H., & Dai, S. (2008) · The Journal of Physical Chemistry B · doi:10.1021/jp808102k · Cited by 76 · see citing works
Self-citationWang, B., Cicerone, M. T., Aso, Y., & Pikal, M. J. (2009) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21960 · Cited by 49 · see citing works
Quasi-elastic neutron scattering in the multi-GPa range and its application to liquid water
Klotz, S., Strässle, T., & Bove, L. E. (2013) · Applied Physics Letters · doi:10.1063/1.4828661 · Cited by 25 · see citing works
Multiple-scattering effects on smooth neutron-scattering spectra
Wuttke, J. (2000) · Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics · doi:10.1103/physreve.62.6531 · Cited by 23 · see citing works
Kalyanram, P., Puri, A., & Gupta, A. R. (2021) · Journal of Thermal Analysis and Calorimetry · doi:10.1007/s10973-021-10929-6 · Cited by 22 · see citing works
Mamontov, E., Cheng, Y. Q., Daemen, L. L., Kolesnikov, A. I., Ramirez-Cuesta, A. J., Ryder, M. R., & Stone, M. B. (2021) · Chemical Physics Letters · doi:10.1016/j.cplett.2021.138727 · Cited by 13 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
A preparation method for mRNA-LNPs with improved properties
Geng, C., Zhou, K., Yan, Y., Li, C., Ni, B., Liu, J., Wang, Y., Zhang, X., Wang, D., Lv, L., et al. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.11.017 · Cited by 71 · see citing works
Backscattering silicon spectrometer (BASIS): sixteen years in advanced materials characterization
Osti, N. C., Jalarvo, N., & Mamontov, E. (2024) · Materials Horizons · doi:10.1039/d4mh00690a · Cited by 23 · see citing works
Self-citationCOVID-19 mRNA Vaccines Preserve Immunogenicity after Re-Freezing
Grau, S., Martín‐García, E., Ferrández, O., Martín, R., Vaquero, S. T., Gimeno, R., Magri, G., & Maldonado, R. J. (2022) · Vaccines · doi:10.3390/vaccines10040594 · Cited by 7 · see citing works
Teko-Agbo, C. A., Josse, E., Konate, K., Deshayes, S., Barbara, P. D. S., Faure, S., Boisguérin, P., & Vivès, É. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102650 · Cited by 4 · see citing works
- Authors
- Mamontov, E., Daemen, L. L., Novak, E., & Stone, M. B.
- Affiliations
- Oak Ridge National Laboratory (US)
- Corresponding author
- Mamontov, Eugene
- Venue
- Medicina
- Publisher
- MDPI AG
- Published
- 2021-12-09
- Volume
- 57
- Issue
- 12
- Pages
- 1343
- ISSN
- 1010-660X (ISSN-L)
- 1648-9144
- PMC
- PMC8706477
- OpenAlex
- W4200339302
- Cited by
- 5
- References
- 13
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2
- FWCI
- 0.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Medicina (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Energy
- Office of Science
- Basic Energy Sciences
- Oak Ridge National Laboratory
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Physical Sciences › Materials Science › Materials Chemistry › Material Dynamics and Properties
- Physical Sciences › Earth and Planetary Sciences › Atmospheric Science › nanoparticles nucleation surface interactions
- Keywords
- BNT162b2, mRNA vaccines, thermal stability, lipid nanoparticles, two-phase morphology, irreversible structural changes, molecular mobility, vibrational spectra, cold storage, vaccine storage stability
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, BNT162 Vaccine, Freezing, Humans
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
