• Paul F McKay, Kai Hu, Anna K Blakney, Karnyart Samnuan, Jonathan C Brown, Rebecca Penn, Jie Zhou, Clément R Bouton, Paul Rogers, Krunal Polra, Paulo J C Lin, Christopher Barbosa, Ying K Tam, Wendy S Barclay, and Robin J Shattock.
• Department of Infectious Diseases, Imperial College London, Norfolk Place, London, W2 1PG, UK.
• Nat Commun. 2020 Jul 9; 11 (1): 3523.

AbstractThe 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.

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