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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
Nature communications, 01/2021, Volume: 12, Issue: 1Journal Article
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.
