Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice
Open accessAbstract
The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-γ production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.
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Two different saRNA vaccines developed independently by Arcturus Therapeutics and Imperial College London have shown favorable immune responses against SARS-CoV-2, and have entered clinical trials.
“Recently, two different saRNA vaccines developed independently by Arcturus Therapeutics and Imperial College London have shown favorable immune responses against SARS-CoV-2, and have entered clinical trials.211–213”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [211]
In mice, 10 ng primer and booster doses of LNP-nCoVsaRNA injected 28 days apart into muscle yielded a robust T cell response and IgG titres similar to those in plasma from patients who had recovered from COVID-19.
“In mice, 10 ng primer and booster doses injected 28 days apart into muscle yielded a robust T cell response and IgG titres similar to those in plasma from patients who had recovered from COVID-19 (ref.136).”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [136]
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- Authors
- McKay, P. F., Hu, K., Blakney, A. K., Samnuan, K., Brown, J. C., Penn, R., Zhou, J., Bouton, C. R., Rogers, P., Polra, K., Lin, P. J. C., Barbosa, C., Tam, Y. K., Barclay, W. S., & Shattock, R. J.
- Affiliations
- Imperial College London (GB)
- Acuitas Therapeutics (Canada) (CA)
- Corresponding author
- Shattock, Robin J.
- ORCID
- Venue
- Nature Communications
- Published
- 2020-07-09
- Volume
- 11
- Issue
- 1
- Pages
- 3523-3523
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7347890
- OpenAlex
- W3041318796
- Cited by
- 462
- References
- 21
- Citations by year
- 2026: 36 · 2025: 48 · 2024: 48 · 2023: 59 · 2022: 102 · 2021: 132 · 2020: 37
- FWCI
- 10.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- European Commission (794059)
- RCUK | Engineering and Physical Sciences Research Council (EP/R013764/1)
- 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
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- SARS-CoV-2, COVID-19 vaccines, self-amplifying RNA, lipid nanoparticle vaccine, spike protein, neutralizing antibodies, Th1 response, antibody-dependent enhancement, interferon-gamma, cell-mediated immunity, vaccine immunogenicity
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Animals, Antibodies, Viral, Disease Models, Animal, Humans, Immunoglobulin G, Immunity, Cellular, Mice, Inbred BALB C, Pneumonia, Viral, RNA, Viral, Vaccines, Synthetic, Viral Vaccines, Cytokines, Coronavirus Infections, Antibody-Dependent Enhancement, Mice, Nanoparticles, Antibodies, Neutralizing, Pandemics, Spike Glycoprotein, Coronavirus
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