Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice
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Published version
Author(s)
Type
Journal Article
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.
Date Issued
2020-07-09
Date Acceptance
2020-06-23
Citation
Nature Communications, 2020, 11 (1), pp.1-7
ISSN
2041-1723
Publisher
Nature Research
Start Page
1
End Page
7
Journal / Book Title
Nature Communications
Volume
11
Issue
1
Copyright Statement
© The Author(s) 2020. This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/32647131
PII: 10.1038/s41467-020-17409-9
Grant Number
EP/R013764/1
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CORONAVIRUS
DELIVERY
Animals
Antibodies, Neutralizing
Antibodies, Viral
Antibody-Dependent Enhancement
Betacoronavirus
COVID-19
COVID-19 Vaccines
Coronavirus Infections
Cytokines
Disease Models, Animal
Humans
Immunity, Cellular
Immunoglobulin G
Mice
Mice, Inbred BALB C
Nanoparticles
Pandemics
Pneumonia, Viral
RNA, Viral
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Vaccines, Synthetic
Viral Vaccines
Animals
Mice, Inbred BALB C
Humans
Mice
Pneumonia, Viral
Coronavirus Infections
Disease Models, Animal
Immunoglobulin G
Vaccines, Synthetic
RNA, Viral
Viral Vaccines
Antibodies, Viral
Cytokines
Antibody-Dependent Enhancement
Immunity, Cellular
Nanoparticles
Antibodies, Neutralizing
Pandemics
Spike Glycoprotein, Coronavirus
Betacoronavirus
COVID-19
SARS-CoV-2
COVID-19 Vaccines
Publication Status
Published
Coverage Spatial
England
Article Number
ARTN 3523
Date Publish Online
2020-07-09