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

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20654-7

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