Effect of mRNA-LNP components of two globally-marketed COVID-19 vaccines on efficacy and stability
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Abstract
During the COVID-19 pandemic, Pfizer-BioNTech and Moderna successfully developed nucleoside-modified mRNA lipid nanoparticle (LNP) vaccines. SARS-CoV-2 spike protein expressed by those vaccines are identical in amino acid sequence, but several key components are distinct. Here, we compared the effect of ionizable lipids, untranslated regions (UTRs), and nucleotide composition of the two vaccines, focusing on mRNA delivery, antibody generation, and long-term stability. We found that the ionizable lipid, SM-102, in Moderna’s vaccine performs better than ALC-0315 in Pfizer-BioNTech’s vaccine for intramuscular delivery of mRNA and antibody production in mice and long-term stability at 4 °C. Moreover, Pfizer-BioNTech’s 5′ UTR and Moderna’s 3′ UTR outperform their counterparts in their contribution to transgene expression in mice. We further found that varying N1-methylpseudouridine content at the wobble position of mRNA has little effect on vaccine efficacy. These findings may contribute to the further improvement of nucleoside-modified mRNA-LNP vaccines and therapeutics.
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- Authors
- Zhang, L., More, K. R., Ojha, A., Jackson, C. B., Quinlan, B. D., Li, H., He, W., Farzan, M., Pardi, N., & Choe, H.
- Affiliations
- Boston Children's Hospital (US)
- The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology (US)
- Scripps Research Institute (US)
- Broad Institute (US)
- University of Pennsylvania (US)
- Corresponding author
- Zhang, Lizhou
- Choe, Hyeryun
- ORCID
- Venue
- npj Vaccines
- Published
- 2023-10-11
- Volume
- 8
- Issue
- 1
- Pages
- 156-156
- ISSN
- 2059-0105 (ISSN-L)
- PMC
- PMC10567765
- OpenAlex
- W4387526062
- Cited by
- 244
- References
- 22
- Citations by year
- 2026: 86 · 2025: 110 · 2024: 45 · 2023: 3
- FWCI
- 21.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Vaccines (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Foundation for the National Institutes of Health (R01 AI129868)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- COVID-19 vaccines, mRNA-LNP vaccine, ionizable lipids, SM-102, ALC-0315, 5' untranslated region, 3' untranslated region, N1-methylpseudouridine, wobble position, nucleoside-modified mRNA, mRNA delivery, antibody response, vaccine stability, SARS-CoV-2 spike protein, BNT162b2, Moderna vaccine
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