Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice

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 ()
Additional contact information
Paul F. McKay: Imperial College London
Kai Hu: Imperial College London
Anna K. Blakney: Imperial College London
Karnyart Samnuan: Imperial College London
Jonathan C. Brown: Imperial College London
Rebecca Penn: Imperial College London
Jie Zhou: Imperial College London
Clément R. Bouton: Imperial College London
Paul Rogers: Imperial College London
Krunal Polra: Imperial College London
Paulo J. C. Lin: Acuitas Therapeutics
Christopher Barbosa: Acuitas Therapeutics
Ying K. Tam: Acuitas Therapeutics
Wendy S. Barclay: Imperial College London
Robin J. Shattock: Imperial College London

Nature Communications, 2020, vol. 11, issue 1, 1-7

Abstract: 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: 2020
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DOI: 10.1038/s41467-020-17409-9

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