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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 & Yin, 2020. "Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice," Nature Communications, Nature, vol. 11(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17409-9
    DOI: 10.1038/s41467-020-17409-9
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    Cited by:

    1. Neeltje van Doremalen & Jonathan E. Schulz & Danielle R. Adney & Taylor A. Saturday & Robert J. Fischer & Claude Kwe Yinda & Nazia Thakur & Joseph Newman & Marta Ulaszewska & Sandra Belij-Rammerstorfe, 2022. "ChAdOx1 nCoV-19 (AZD1222) or nCoV-19-Beta (AZD2816) protect Syrian hamsters against Beta Delta and Omicron variants," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Ravindra B. Malabadi & Kiran P. Kolkar & Neelambika T. Meti & Raju K. Chalannavar, 2021. "Vaccine Development for Coronavirus (SARS-CoV-2) Disease (Covid-19); Lipid Nanoparticles," International Journal of Research and Scientific Innovation, International Journal of Research and Scientific Innovation (IJRSI), vol. 8(3), pages 189-195, March.
    3. Roy Pattipeiluhu & Ye Zeng & Marco M.R.M. Hendrix & Ilja K. Voets & Alexander Kros & Thomas H. Sharp, 2024. "Liquid crystalline inverted lipid phases encapsulating siRNA enhance lipid nanoparticle mediated transfection," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Mai Komori & Takuto Nogimori & Amber L. Morey & Takashi Sekida & Keiko Ishimoto & Matthew R. Hassett & Yuji Masuta & Hirotaka Ode & Tomokazu Tamura & Rigel Suzuki & Jeff Alexander & Yasutoshi Kido & K, 2023. "saRNA vaccine expressing membrane-anchored RBD elicits broad and durable immunity against SARS-CoV-2 variants of concern," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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