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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antibodies, Neutralizing / immunology*
-
Antibodies, Viral / blood
-
Antibodies, Viral / metabolism
-
Antibody-Dependent Enhancement / immunology
-
Betacoronavirus / genetics
-
Betacoronavirus / immunology*
-
COVID-19
-
COVID-19 Vaccines
-
Coronavirus Infections / immunology
-
Coronavirus Infections / prevention & control*
-
Coronavirus Infections / virology
-
Cytokines / immunology
-
Disease Models, Animal
-
Humans
-
Immunity, Cellular
-
Immunoglobulin G / blood
-
Mice
-
Mice, Inbred BALB C
-
Nanoparticles / chemistry*
-
Pandemics / prevention & control*
-
Pneumonia, Viral / immunology
-
Pneumonia, Viral / prevention & control*
-
Pneumonia, Viral / virology
-
RNA, Viral / immunology
-
SARS-CoV-2
-
Spike Glycoprotein, Coronavirus / genetics
-
Spike Glycoprotein, Coronavirus / immunology
-
Vaccines, Synthetic / chemistry
-
Vaccines, Synthetic / immunology
-
Viral Vaccines / chemistry
-
Viral Vaccines / immunology*
Substances
-
Antibodies, Neutralizing
-
Antibodies, Viral
-
COVID-19 Vaccines
-
Cytokines
-
Immunoglobulin G
-
RNA, Viral
-
Spike Glycoprotein, Coronavirus
-
Vaccines, Synthetic
-
Viral Vaccines
-
spike protein, SARS-CoV-2