Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-020-20654-7
Keywords
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Categories
Funding
- Townsend-Jeantet Charitable Trust [1011770]
- EPA Cephalosporin Early Career Researcher Fund
- Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China [2018-I2M-2-002]
- Francis Crick Institute
- Medical Research Council [FC001030]
- Wellcome Trust [FC001030]
- CAMS Innovation Fund [AJR00750]
- CAMS-CIFMS, China [2018-I2M-2-002]
- UK Medical Research Council [MR/N00065X/1]
- Cancer Research UK [FC001030, C20724/A14414, C20724/A26752]
- UKRI Biotechnology and Biological Sciences Research Council (BBSRC) [BBS/E/I/00007031, BBS/E/I/00007034, BBS/E/I/00007037, BBS/E/I/00007039]
- Bill and Melinda Gates Foundation [OPP1215550]
- EPSRC [EP/S025243/1]
- UK Department for Environment Food and Rural Affairs [SE26081]
- BBSRC [BBS/E/I/00007034, BBS/E/I/00007038, BBS/E/I/00007031, BB/S007911/1, BBS/E/I/00007037, BBS/E/I/00007039, BBS/E/I/COV07000] Funding Source: UKRI
- MRC [MR/N00065X/1] Funding Source: UKRI
- Bill and Melinda Gates Foundation [OPP1215550] Funding Source: Bill and Melinda Gates Foundation
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This study introduces a potential vaccine candidate against SARS-CoV-2, utilizing a synthetic virus-like particle platform to present the receptor-binding domain of the virus spike protein. The vaccine induces strong neutralizing antibody responses in mice and pigs, demonstrating thermostability and the potential for global distribution.
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.
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