A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

Tiong Kit Tan*, Pramila Rijal, Rolle Rahikainen, Anthony H. Keeble, Lisa Schimanski, Saira Hussain, Ruth Harvey, Jack W.P. Hayes, Jane C. Edwards, Rebecca K. McLean, Veronica Martini, Miriam Pedrera, Nazia Thakur, Carina Conceicao, Isabelle Dietrich, Holly Shelton, Anna Ludi, Ginette Wilsden, Clare Browning, Adrian K. ZagrajekDagmara Bialy, Sushant Bhat, Phoebe Stevenson-Leggett, Philippa Hollinghurst, Matthew Tully, Katy Moffat, Chris Chiu, Ryan Waters, Ashley Gray, Mehreen Azhar, Valerie Mioulet, Joseph Newman, Amin S. Asfor, Alison Burman, Sylvia Crossley, John A. Hammond, Elma Tchilian, Bryan Charleston, Dalan Bailey, Tobias J. Tuthill, Simon P. Graham, Helen M.E. Duyvesteyn, Tomas Malinauskas, Jiandong Huo, Julia A. Tree, Karen R. Buttigieg, Raymond J. Owens, Miles Carroll, Rodney S. Daniels, John W. McCauley, David I. Stuart, Kuan Ying A. Huang, Mark Howarth, Alain R. Townsend

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine against SARS-CoV-2. The vaccine is based on the display of coronavirus spike glycoprotein receptor-binding domain (RBD) on a synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses of RBD-SpyVLP in a prime-boost regimen induce a strong neutralising antibody response in mice and pigs that is superior to convalescent human sera. We evaluate antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we show that RBD-SpyVLP induces a polyclonal antibody response that recognises key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. Moreover, RBD-SpyVLP is thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence. The data suggests that RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic. Vaccines for SARS-COV-2 are needed in the ongoing pandemic. Here the authors characterize a vaccine candidate that presents the receptor-binding domain (RBD) of SARS-CoV-2 spike protein on a synthetic VLP platform using SpyTag/SpyCatcher technology and show immunogenicity of a prime-boost regimen in mice and pigs.

Original languageEnglish
Article number542
Number of pages16
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 22 Jan 2021

Bibliographical note

Funding Information:
T.K.T. is funded by the Townsend-Jeantet Charitable Trust (charity number 1011770) and the EPA Cephalosporin Early Career Researcher Fund. P.R., L.S. and A.R.T. are funded by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant no. 2018-I2M-2-002). The work done at the Crick Worldwide Influenza Centre was supported by the Francis Crick Institute, receiving core funding from Cancer Research UK (FC001030), the Medical Research Council (FC001030) and the Wellcome Trust (FC001030). Cryo-Electron microscopy analysis was supported by the CAMS Innovation Fund (AJR00750). H.M.E.D. and D.I.S. were funded by the CAMS-CIFMS, China (grant no. 2018-I2M-2-002). D.I.S. was also supported by the UK Medical Research Council (MR/N00065X/1). T.M. is supported by Cancer Research UK grants C20724/A14414 and C20724/A26752 to Christian Siebold. The pig study was supported by UKRI Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme and Core Capability Grants to The Pirbright Institute (BBS/E/I/00007031, BBS/E/I/00007034, BBS/E/I/00007037 and BBS/E/ I/00007039), and the Bill and Melinda Gates Foundation supported ‘Pirbright Livestock Antibody Hub’ (Grant No. OPP1215550). Development of SARS-CoV-2 reagents was partially supported by EPSRC Grant No. EP/S025243/1 to the Rosalind Franklin Institute. A.L., G.W., C.B., A.B., and V.M. are supported by the UK Department for Environment Food and Rural Affairs (Grant No. SE26081). We thank The Pirbright Institute Animal Services Team for animal care and provision of samples.

Publisher Copyright:
© 2021, The Author(s).

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • MODEL
  • VISUALIZATION
  • PIG

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