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

Tan Hyon-Xhi; 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; Adam K Wheatley

Journal article

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

Tan Hyon-Xhi, 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, Adam K Wheatley

NATURE COMMUNICATIONS | NATURE PORTFOLIO | Published : 2021

DOI: 10.1038/s41467-021-21665-8

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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-focussi..

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University of Melbourne Researchers

Jennifer Juno Author Microbiology and Immunology

Robyn Esterbauer Author Microbiology and Immunology

Adam Wheatley Author Microbiology and Immunology

Stephen Kent Author Microbiology and Immunology

Francesca Mordant Author Microbiology and Immunology

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Awarded by Victorian Government

Awarded by Medical Research Future Fund (MRFF)

Awarded by NHMRC

Awarded by NHMRC-EU collaborative award

Awarded by European Union Horizon 2020 Research and Innovation Programme

Funding Acknowledgements

We thank the generous participation of the trial subjects for providing samples. The SARS-CoV-2 RBD expression plasmids were kindly provided by Florian Krammer, Mt. Sinai School of Medicine, NY, USA. The human and mouse ACE2 expression plasmids were kindly provided by Merlin Thomas, Monash University, Australia. We acknowledge the Melbourne Cytometry Platform (Melbourne Brain Centre node) for provision of flow cytometry services. We thank Robin Shattock (Imperial College London) and Dietmar Katinger and Philipp Mundsperger from Polymun for provision of the MPLA liposome adjuvant. This study was supported by the Victorian Government and Medical Research Future Fund (MRFF) GNT2002073 (SJK and AKW), the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology (SJK), an NHMRC programme grant APP1149990 (SJK), an NHMRC project grant GNT1162760 (AKW), an NHMRC-EU collaborative award APP1115828 (SJK), the European Union Horizon 2020 Research and Innovation Programme under grant agreement 681137 (SJK), the Jack Ma Foundation (KS) and the A2 Milk Company (KS). J.A.J. and S.J.K. are supported by NHMRC fellowships. A.K.W. and K.S. are supported by NHMRC Investigator grants. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health.