Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity
Cyrielle Fougeroux, Louise Goksøyr, Manja Idorn, Vladislav Soroka, Sebenzile K. Myeni, Robert Dagil, Christoph M. Janitzek, Max Søgaard, Kara-Lee Aves, Emma Wenzel Horsted, Sayit Mahmut Erdoğan, Tobias Gustavsson, Jerzy Dorosz, Stine B. Clemmensen, Laurits Fredsgaard, Susan Thrane, Elena Ethel Vidal-Calvo, Paul Khalifé, Thomas Morgan Hulen, Swati Choudhary, Michael Theisen, Susheel Kumar Singh, Asier Garcia-Senosiain, Linda van Oosten, Gorben P. Pijlman, Bettina Hierzberger, Tanja Domeyer, Blanka W. Nalewajek, Anette Strøbæk, Magdalena Skrzypczak, Laura F. Andersson, Søren Buus, Anette Stryhn Buus, Jan Pravsgaard Christensen, Tim J. Dalebout, Kasper Iversen, Lene Holm Harritshøj, Benjamin Mordmüller, Henrik Ullum, Line S. Reinert, Willem A. de Jongh, Marjolein Kikkert, Søren R. Paludan, Thor G. Theander, Morten A. Nielsen, Ali Salanti, Adam F. Sander
Abstract
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.