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

DOI: 10.1038/s41467-020-20654-7 DOI Help

Authors: 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 Institut) , 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; University of Surrey) , 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 (University of Oxford) , Tomas Malinauskas (University of Oxford) , Jiandong Huo (University of Oxford; Research Complex at Harwell; Rosalind Franklin Institute) , Julia A. Tree (Public Health England) , Karen R. Buttigieg (Public Health England) , Raymond J. Owens (University of Oxford; Research Complex at Harwell; Rosalind Franklin Institute) , Miles W. Carroll (Public Health England; University of Oxford) , Rodney S. Daniels (The Francis Crick Institute) , John W. Mccauley (The Francis Crick Institute) , David I. Stuart (University of Oxford; Diamond Light Source) , Kuan-Ying A. Huang (Chang Gung University) , Mark Howarth (University of Oxford) , Alain R. Townsend (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 12

State: Published (Approved)
Published: January 2021

Open Access Open Access

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.

Journal Keywords: Preclinical research; Protein vaccines; SARS-CoV-2; Viral infection

Diamond Keywords: COVID-19; Viruses

Subject Areas: Biology and Bio-materials, Medicine

Technical Areas:


Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Drug Discovery Infectious Diseases Pathogens Vaccines Structural biology Chemistry Biochemistry

Technical Tags: