CoChat
Sign Up
Cited by 464SARS-CoV-2 and COVID-19 ResearchRNA Interference and Gene DeliverySARS-CoV-2 detection and testing

The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.

Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice

Open access
McKay, Paul F., Hu, Kai, Blakney, Anna K., Samnuan, Karnyart, Brown, Jonathan C., Penn, Rebecca, Zhou, Jie, Bouton, Clément R., Rogers, Paul, Polra, Krunal, Lin, Paulo J. C., Barbosa, Christopher, Tam, Ying K., Barclay, Wendy S., Shattock, Robin J.·2020·Nature Communications
DOI 10.1038/s41467-020-17409-9PMC PMC7347890
Open this paper in CoChat — free accountOpen PDF

Abstract

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.

Overview

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-020-17409-9

Cites

21 of 21 references verified0 citation errors · 0 not checkable

Statistics

Figures

Fig. 1 Antibody quantification and neutralization of a SARS-CoV-2 saRNA vaccinated mice compared to COVID-19 recovered patients. a Schematic of vaccination of BALB/c mice with saRNA encoding pre-fusion stabilized spike protein in LNP, b SARS-CoV-2 specific IgG responses in mice vaccinated with doses of LNP-formulated saRNA ranging from 0.01–10 μg of saRNA with n = 7 biologically independent animals and COVID-19 recovered patients with n = 9 biologically independent samples, c SARS-CoV-2 pseudotyped virus neutralization of sera from BALB/c mice vaccinated with doses of LNP-formulated saRNA ranging from 0.01–10 μg of saRNA with n = 7 biologically independent animals and COVID-19 recovered patients with n = 9 biologically independent samples, d Correlation between SARS-CoV-2-specific IgG and SARS-CoV-2 neutralization IC50 for vaccinated mice (n = 7 biologically independent animals) and recovered COVID-19 patients (n = 9 biologically independent samples), e SARS-CoV-2 viral neutralization of sera from BALB/c mice vaccinated with doses of LNP-formulated saRNA ranging from 0.01 to 10 µg of saRNA with n = 7 biologically independent animals, f Correlation between SARS-CoV-2-specific IgG and SARS-CoV-2 wild type viral neutralization titers for vaccinated mice (n = 7 biologically independent animals). Electroporated pDNA (DNA + EP) was used as a positive control while saRNA encoding the rabies glycoprotein (RABV) in pABOL was used as a negative control (RABV control). * indicates significance of p < 0.05 using a two-way ANOVA adjusted for multiple comparisons. Line and error bars indicated mean ± SD. Components of this figure were created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://creativecommons.org/licenses/by/3.0/.
Fig. 1 Antibody quantification and neutralization of a SARS-CoV-2 saRNA vaccinated mice compared to COVID-19 recovered patients. a Schematic of vaccination of BALB/c mice with saRNA encoding pre-fusion stabilized spike protein in LNP, b SARS-CoV-2 specific IgG responses in mice vaccinated with doses of LNP-formulated saRNA ranging from 0.01–10 μg of saRNA with n = 7 biologically independent animals and COVID-19 recovered patients with n = 9 biologically independent samples, c SARS-CoV-2 pseudotyped virus neutralization of sera from BALB/c mice vaccinated with doses of LNP-formulated saRNA ranging from 0.01–10 μg of saRNA with n = 7 biologically independent animals and COVID-19 recovered patients with n = 9 biologically independent samples, d Correlation between SARS-CoV-2-specific IgG and SARS-CoV-2 neutralization IC50 for vaccinated mice (n = 7 biologically independent animals) and recovered COVID-19 patients (n = 9 biologically independent samples), e SARS-CoV-2 viral neutralization of sera from BALB/c mice vaccinated with doses of LNP-formulated saRNA ranging from 0.01 to 10 µg of saRNA with n = 7 biologically independent animals, f Correlation between SARS-CoV-2-specific IgG and SARS-CoV-2 wild type viral neutralization titers for vaccinated mice (n = 7 biologically independent animals). Electroporated pDNA (DNA + EP) was used as a positive control while saRNA encoding the rabies glycoprotein (RABV) in pABOL was used as a negative control (RABV control). * indicates significance of p < 0.05 using a two-way ANOVA adjusted for multiple comparisons. Line and error bars indicated mean ± SD. Components of this figure were created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://creativecommons.org/licenses/by/3.0/.CC BY · PubMed Central
Fig. 2 Th1/Th2 skew in response to SARS-CoV-2 saRNA LNP vaccine. a IgG1 and IgG2a responses in mice vaccinated with doses of LNP-formulated saRNA ranging from 0.01–10 μg of saRNA with n = 7 biologically independent animals, b Th1/Th2 skewing responses in mice vaccinated with doses of LNP-formulated saRNA ranging from 0.01–10 μg of saRNA with n = 7 biologically independent animals, and 10 μg of electroporated pDNA (EP pDNA) with n = 8 biologically independent animals. The asterisk (*) indicates significance of p < 0.05 as determined by a Kruskal–Wallis test. Line and error bars indicated mean ± SD.
Fig. 2 Th1/Th2 skew in response to SARS-CoV-2 saRNA LNP vaccine. a IgG1 and IgG2a responses in mice vaccinated with doses of LNP-formulated saRNA ranging from 0.01–10 μg of saRNA with n = 7 biologically independent animals, b Th1/Th2 skewing responses in mice vaccinated with doses of LNP-formulated saRNA ranging from 0.01–10 μg of saRNA with n = 7 biologically independent animals, and 10 μg of electroporated pDNA (EP pDNA) with n = 8 biologically independent animals. The asterisk (*) indicates significance of p < 0.05 as determined by a Kruskal–Wallis test. Line and error bars indicated mean ± SD.CC BY · PubMed Central
Fig. 3 Cellular and secreted cytokine responses to a SARS-CoV-2 saRNA LNP vaccine. a Quantification of IFN-γ splenocytes upon restimulation with SARS-CoV-2 peptides, expressed as spot forming units (SFU) per 106 cells with n = 7 biologically independent animals. Electroporated pDNA (EP pDNA) was used as a positive control while saRNA encoding the rabies glycoprotein (RABV) in pABOL was used as a negative control (RABV control). b–g Cytokine profile in sera of mice 4 h after vaccination with SARS-CoV-2 LNP vaccine with n = 7 biologically independent animals. Remaining cytokines can be found in Supplementary Fig. 5. The asterisk (*) indicates significance of p < 0.05 as determined by a Kruskal–Wallis test. Line and error bars indicated mean ± SD.
Fig. 3 Cellular and secreted cytokine responses to a SARS-CoV-2 saRNA LNP vaccine. a Quantification of IFN-γ splenocytes upon restimulation with SARS-CoV-2 peptides, expressed as spot forming units (SFU) per 106 cells with n = 7 biologically independent animals. Electroporated pDNA (EP pDNA) was used as a positive control while saRNA encoding the rabies glycoprotein (RABV) in pABOL was used as a negative control (RABV control). b–g Cytokine profile in sera of mice 4 h after vaccination with SARS-CoV-2 LNP vaccine with n = 7 biologically independent animals. Remaining cytokines can be found in Supplementary Fig. 5. The asterisk (*) indicates significance of p < 0.05 as determined by a Kruskal–Wallis test. Line and error bars indicated mean ± SD.CC BY · PubMed Central

Verification

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.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 21 references

Cited by

Sorted by citations

Related

See all

Metadata

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
Publisher
Springer Science and Business Media LLC
Published
2020-07-09
Volume
11
Issue
1
Pages
3523-3523
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-020-17409-9
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
Licence
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

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