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

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

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 vaccine is a highly promising candidate for preventing COVID-19.

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Bibliographic Details
Main Authors: Fougeroux, Cyrielle, Goksøyr, Louise, Idorn, Manja, Soroka, Vladislav, Myeni, Sebenzile K., Dagil, Robert, Janitzek, Christoph M., Søgaard, Max, Aves, Kara Lee, Horsted, Emma W., Erdoğan, Sayit Mahmut, Gustavsson, Tobias, Dorosz, Jerzy, Clemmensen, Stine, Fredsgaard, Laurits, Thrane, Susan, Vidal-Calvo, Elena E., Khalifé, Paul, Hulen, Thomas M., Choudhary, Swati, Theisen, Michael, Singh, Susheel K., Garcia-Senosiain, Asier, Van Oosten, Linda, Pijlman, Gorben, Hierzberger, Bettina, Domeyer, Tanja, Nalewajek, Blanka W., Strøbæk, Anette, Skrzypczak, Magdalena, Andersson, Laura F., Buus, Søren, Buus, Anette Stryhn, Christensen, Jan Pravsgaard, Dalebout, Tim J., Iversen, Kasper, Harritshøj, Lene H., Mordmüller, Benjamin, Ullum, Henrik, Reinert, Line S., de Jongh, Willem Adriaan, Kikkert, Marjolein, Paludan, Søren R., Theander, Thor G., Nielsen, Morten A., Salanti, Ali, Sander, Adam F.
Format: Article/Letter to editor biblioteca
Language:English
Subjects:Life Science,
Online Access:https://research.wur.nl/en/publications/capsid-like-particles-decorated-with-the-sars-cov-2-receptor-bind
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Summary: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 vaccine is a highly promising candidate for preventing COVID-19.

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