A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity
Open accessAbstract
Although inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core–shell structured lipopolyplex (LPP) nanoparticles. SW0123 is easy to produce using a large-scale microfluidics-based apparatus. The unique core–shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability, and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration. Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123, represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2, but also a panel of variants including D614G and N501Y variants. In addition, SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge. Taken together, SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.
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The benchmark sequence H has been used in a COVID-19 mRNA vaccine that elicited high immunogenicity in two animal models and entered a phase I clinical trial in China.
“This benchmark sequence has been used in a COVID-19 mRNA vaccine that elicited high immunogenicity in two animal models26 and entered a phase I clinical trial in China”
From Algorithm for optimized mRNA design improves stability and immunogenicity (2023) · cites this paper as [26]
The Introduction reports that SW0123 was highly immunogenic in mice and nonhuman primates and was being evaluated in a Phase I clinical trial in China. The Results describe its sequence-optimized spike mRNA, but our copy does not identify that mRNA as the citing document’s benchmark sequence H, so the claimed link to H is not established. (LLM, conf=0.85)
Experimental — accuracy not yet measuredLPP is a lipid-based mRNA delivery system and has been demonstrated to provide high efficacy and good safety profile.
“LPP is a lipid-based mRNA delivery system and has been demonstrated to provide high efficacy and good safety profile26.”
From Algorithm for optimized mRNA design improves stability and immunogenicity (2023) · cites this paper as [26]
The Introduction identifies LPP as a lipid-shell mRNA delivery platform, and the Discussion describes an LPP-based COVID-19 vaccine as highly efficacious. The Results report protection in animal challenge models and mild reactogenicity in safety testing. These findings support efficacy and a favorable safety profile for the tested vaccine, SW0123, but do not establish them for LPP-based mRNA delivery generally. (LLM, conf=0.84)
Experimental — accuracy not yet measuredYang and colleagues applied similar LPP technology to encapsulate mRNA in two steps using ionizable lipid, DOPE and PEG-lipid to generate COVID-19 mRNA vaccine with a core-shell structure, which showed significant protection in mice and non-human primates.
“Yang and colleagues330 applied similar LPP technology to encapsulate mRNA in two steps using ionizable lipid, DOPE and PEG-lipid to generate COVID-19 mRNA vaccine with a core-shell structure, which showed significant protection in mice and non-human primates.”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [330]
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- Authors
- Yang, R., Deng, Y., Huang, B., Huang, L., Lin, A., Li, Y., Wang, W., Liu, J., Lu, S., Zhan, Z., Wang, Y., A, R., Wang, W., Niu, P., Zhao, L., Li, S., Ma, X., Zhang, L., Zhang, Y., Yao, W., Liang, X., Zhao, J., Liu, Z., Peng, X., Li, H., & Tan, W.
- Affiliations
- Chinese Center For Disease Control and Prevention (CN)
- National Institutes for Food and Drug Control (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Tongji University (CN)
- Chinese Academy of Sciences (CN)
- First Affiliated Hospital of Guangzhou Medical University (CN)
- Corresponding author
- Peng, Xiaozhong
- Li, Hangwen
- Tan, Wenjie
- ORCID
- Venue
- Signal Transduction and Targeted Therapy
- Published
- 2021-05-31
- Volume
- 6
- Issue
- 1
- Pages
- 213-213
- ISSN
- 2059-3635 (ISSN-L)
- PMC
- PMC8165147
- OpenAlex
- W3164764657
- Cited by
- 130
- References
- 49
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 30 · 2023: 38 · 2022: 25 · 2021: 10
- FWCI
- 8.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Greater South Information System
- Funders
- National Natural Science Foundation of China (82061138008, 82041041, 82061138008, COVID-19, 82041041)
- National Key Research and Development Program of China (2016YFD0500301, 2020YFC0842200, 2020YFC0840900)
- 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
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- COVID-19 mRNA vaccine, SARS-CoV-2 spike protein, core-shell nanoparticles, tissue distribution, liver targeting, neutralizing antibodies, SARS-CoV-2 variants, D614G mutation, vaccine protection
- MeSH terms
- Immunogenicity, Vaccine, COVID-19, SARS-CoV-2, COVID-19 Vaccines, mRNA Vaccines, Animals, Antibodies, Viral, Female, Humans, Lymphocyte Activation, Vaccines, Synthetic, Viral Vaccines, Th1 Cells, Mice, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
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