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Fougeroux, C.; Goksoyr, L.; Idorn, M.; Soroka, V.; Myeni, S.K.; Dagil, R.; ... ; Sander, A.F. (2021)

Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity

Article / Letter to editor
The rapid development of a SARS-CoV-2 vaccine is a global priority. Here, we develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. RBD antigens are displayed on AP205 CLPs through a split-protein Tag/Catcher, ensuring unidirectional and high-density display of RBD. Both soluble recombinant RBD and RBD displayed on CLPs bind the ACE2 receptor with nanomolar affinity. Mice are vaccinated with soluble RBD or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. The RBD-CLP vaccines induce higher levels of serum anti-spike antibodies than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice elicits virus neutralization antibody titers comparable to those found in patients that had recovered from COVID-19. Following booster vaccinations, the virus neutralization titers exceed those measured after natural infection, at serum dilutions above 1:10,000. Thus, the RBD-CLP...Show moreThe rapid development of a SARS-CoV-2 vaccine is a global priority. Here, we develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. RBD antigens are displayed on AP205 CLPs through a split-protein Tag/Catcher, ensuring unidirectional and high-density display of RBD. Both soluble recombinant RBD and RBD displayed on CLPs bind the ACE2 receptor with nanomolar affinity. Mice are vaccinated with soluble RBD or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. The RBD-CLP vaccines induce higher levels of serum anti-spike antibodies than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice elicits virus neutralization antibody titers comparable to those found in patients that had recovered from COVID-19. Following booster vaccinations, the virus neutralization titers exceed those measured after natural infection, at serum dilutions above 1:10,000. Thus, the RBD-CLP vaccine is a highly promising candidate for preventing COVID-19.Show less
All authors
Fougeroux, C.; Goksoyr, L.; Idorn, M.; Soroka, V.; Myeni, S.K.; Dagil, R.; Janitzek, C.M.; Sogaard, M.; Aves, K.L.; Horsted, E.W.; Erdogan, S.M.; Gustavsson, T.; Dorosz, J.; Clemmensen, S.; Fredsgaard, L.; Thrane, S.; Vidal-Calvo, E.E.; Khalife, P.; Hulen, T.M.; Choudhary, S.; Theisen, M.; Singh, S.K.; Garcia-Senosiain, A.; Oosten, L. van; Pijlman, G.; Hierzberger, B.; Domeyer, T.; Nalewajek, B.W.; Strobaek, A.; Skrzypczak, M.; Andersson, L.F.; Buus, S.; Buus, A.S.; Christensen, J.P.; Dalebout, T.J.; Iversen, K.; Harritshoj, L.H.; Mordmuller, B.; Ullum, H.; Reinert, L.S.; Jongh, W.A. de; Kikkert, M.; Paludan, S.R.; Theander, T.G.; Nielsen, M.A.; Salanti, A.; Sander, A.F.
Date
2021-01-12
Journal
Nature Communications
Volume
12
Issue
1
DOI
doi:10.1038/s41467-020-20251-8
Link
https://www.nature.com/articles/s41467-020-20251-8.pdf