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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

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, Alain R. Townsend

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AbstractThere 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.