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.
Highlights
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
All of the self-amplifying RNA (saRNA) lipid nanoparticle (LNP)-vaccinated mice, even the 0.01 μg group, had higher quantities of SARS-CoV-2 specific IgG compared to patients that had recovered from COVID-19, which had a mean titer of 103 ng mL−1 and a range of 101–105 ng mL−1
Here we characterized the immunogenicity of a SARS-CoV-2 saRNA LNP vaccine compared to the immune response of a natural infection in COVID-19 recovered patients
Summary
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. 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. We compare the immunogenicity of saRNA encoding a pre-fusion stabilized SARS-CoV-2 spike protein encapsulated in LNP in a preclinical murine model to the immune response generated by a natural infection in recovered COVID-19 patients. We characterize both the humoral and cellular response as well as the neutralization capacity of a pseudotyped and wild-type SARSCoV-2 virus
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