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Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice.
Nat Commun. 2020 07 09; 11(1):3523.NC

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.

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Publisher Full Text
ncbi.nlm.nih.gov
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Authors+Show Affiliations

McKay PF
Department of Infectious Diseases, Imperial College London, Norfolk Place, London, W2 1PG, UK.
Hu K
Department of Infectious Diseases, Imperial College London, Norfolk Place, London, W2 1PG, UK.
Blakney AK
Department of Infectious Diseases, Imperial College London, Norfolk Place, London, W2 1PG, UK.
Samnuan K
Department of Infectious Diseases, Imperial College London, Norfolk Place, London, W2 1PG, UK.
Brown JC
Department of Infectious Diseases, Imperial College London, Norfolk Place, London, W2 1PG, UK.
Penn R
Department of Infectious Diseases, Imperial College London, Norfolk Place, London, W2 1PG, UK.
Zhou J
Department of Infectious Diseases, Imperial College London, Norfolk Place, London, W2 1PG, UK.
Bouton CR
Department of Infectious Diseases, Imperial College London, Norfolk Place, London, W2 1PG, UK.
Rogers P
Department of Infectious Diseases, Imperial College London, Norfolk Place, London, W2 1PG, UK.
Polra K
Department of Infectious Diseases, Imperial College London, Norfolk Place, London, W2 1PG, UK.
Lin PJC
Acuitas Therapeutics, Vancouver, BC, V6T 1Z3, Canada.
Barbosa C
Acuitas Therapeutics, Vancouver, BC, V6T 1Z3, Canada.
Tam YK
Acuitas Therapeutics, Vancouver, BC, V6T 1Z3, Canada.
Barclay WS
Department of Infectious Diseases, Imperial College London, Norfolk Place, London, W2 1PG, UK.
Shattock RJ
Department of Infectious Diseases, Imperial College London, Norfolk Place, London, W2 1PG, UK. r.shattock@imperial.ac.uk.

MeSH

AnimalsAntibodies, NeutralizingAntibodies, ViralAntibody-Dependent EnhancementBetacoronavirusCOVID-19COVID-19 VaccinesCoronavirus InfectionsCytokinesDisease Models, AnimalHumansImmunity, CellularImmunoglobulin GMiceMice, Inbred BALB CNanoparticlesPandemicsPneumonia, ViralRNA, ViralSARS-CoV-2Spike Glycoprotein, CoronavirusVaccines, SyntheticViral Vaccines

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32647131

Citation

McKay, Paul F., et al. "Self-amplifying RNA SARS-CoV-2 Lipid Nanoparticle Vaccine Candidate Induces High Neutralizing Antibody Titers in Mice." Nature Communications, vol. 11, no. 1, 2020, p. 3523.
McKay PF, Hu K, Blakney AK, et al. Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice. Nat Commun. 2020;11(1):3523.
McKay, P. F., Hu, K., Blakney, A. K., Samnuan, K., Brown, J. C., Penn, R., Zhou, J., Bouton, C. R., Rogers, P., Polra, K., Lin, P. J. C., Barbosa, C., Tam, Y. K., Barclay, W. S., & Shattock, R. J. (2020). Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice. Nature Communications, 11(1), 3523. https://doi.org/10.1038/s41467-020-17409-9
McKay PF, et al. Self-amplifying RNA SARS-CoV-2 Lipid Nanoparticle Vaccine Candidate Induces High Neutralizing Antibody Titers in Mice. Nat Commun. 2020 07 9;11(1):3523. PubMed PMID: 32647131.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice. AU - McKay,Paul F, AU - Hu,Kai, AU - Blakney,Anna K, AU - Samnuan,Karnyart, AU - Brown,Jonathan C, AU - Penn,Rebecca, AU - Zhou,Jie, AU - Bouton,Clément R, AU - Rogers,Paul, AU - Polra,Krunal, AU - Lin,Paulo J C, AU - Barbosa,Christopher, AU - Tam,Ying K, AU - Barclay,Wendy S, AU - Shattock,Robin J, Y1 - 2020/07/09/ PY - 2020/06/02/received PY - 2020/06/23/accepted PY - 2020/7/11/entrez PY - 2020/7/11/pubmed PY - 2020/7/22/medline SP - 3523 EP - 3523 JF - Nature communications JO - Nat Commun VL - 11 IS - 1 N2 - 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. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/32647131/Self_amplifying_RNA_SARS_CoV_2_lipid_nanoparticle_vaccine_candidate_induces_high_neutralizing_antibody_titers_in_mice_ L2 - https://doi.org/10.1038/s41467-020-17409-9 DB - PRIME DP - Unbound Medicine ER -