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

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. Kent () and Adam K. Wheatley ()
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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
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
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
Stephen J. Kent: University of Melbourne, at The Peter Doherty Institute for Infection and Immunity
Adam K. Wheatley: University of Melbourne, at The Peter Doherty Institute for Infection and Immunity

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21665-8

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