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