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

Cyrielle FougerouxLouise GoksøyrManja IdornVladislav SorokaSebenzile K MyeniRobert DagilChristoph M JanitzekMax SøgaardKara-Lee AvesEmma W HorstedSayit Mahmut ErdoğanTobias GustavssonJerzy DoroszStine ClemmensenLaurits FredsgaardSusan ThraneElena Ethel Vidal-CalvoPaul KhaliféThomas M HulenSwati ChoudharyMichael TheisenSusheel K SinghAsier Garcia-SenosiainLinda Van OostenGorben P PijlmanBettina HierzbergerTanja DomeyerBlanka W NalewajekAnette StrøbækMagdalena SkrzypczakLaura F AnderssonSoren BuusAnette Stryhn BuusJan Pravsgaard ChristensenTim J DaleboutKasper IversenLene H HarritshøjBenjamin MordmüllerHenrik UllumLine S ReinertWillem Adriaan de JonghMarjolein KikkertSoren Riis PaludanThor G TheanderMorten Agertoug NielsenAli SalantiAdam Frederik Sander
Published in: Nature communications (2021)
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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