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Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques

Author

Listed:
  • Hyon-Xhi Tan

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Jennifer A. Juno

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Wen Shi Lee

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Isaac Barber-Axthelm

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Hannah G. Kelly

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity
    University of Melbourne)

  • Kathleen M. Wragg

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Robyn Esterbauer

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity
    WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity)

  • Thakshila Amarasena

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Francesca L. Mordant

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Kanta Subbarao

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity
    WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity)

  • Stephen J. Kent

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity
    University of Melbourne
    Monash University)

  • Adam K. Wheatley

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity
    University of Melbourne)

Abstract

SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD is associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augments neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines are comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.

Suggested Citation

  • Hyon-Xhi Tan & Jennifer A. Juno & Wen Shi Lee & Isaac Barber-Axthelm & Hannah G. Kelly & Kathleen M. Wragg & Robyn Esterbauer & Thakshila Amarasena & Francesca L. Mordant & Kanta Subbarao & Stephen J., 2021. "Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21665-8
    DOI: 10.1038/s41467-021-21665-8
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    Cited by:

    1. Oskar Staufer & Kapil Gupta & Jochen Estebano Hernandez Bücher & Fabian Kohler & Christian Sigl & Gunjita Singh & Kate Vasileiou & Ana Yagüe Relimpio & Meline Macher & Sebastian Fabritz & Hendrik Diet, 2022. "Synthetic virions reveal fatty acid-coupled adaptive immunogenicity of SARS-CoV-2 spike glycoprotein," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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