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


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.

SUBMITTER: Fougeroux C 

PROVIDER: S-EPMC7804149 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Fougeroux Cyrielle C   Goksøyr Louise L   Idorn Manja M   Soroka Vladislav V   Myeni Sebenzile K SK   Dagil Robert R   Janitzek Christoph M CM   Søgaard Max M   Aves Kara-Lee KL   Horsted Emma W EW   Erdoğan Sayit Mahmut SM   Gustavsson Tobias T   Dorosz Jerzy J   Clemmensen Stine S   Fredsgaard Laurits L   Thrane Susan S   Vidal-Calvo Elena E EE   Khalifé Paul P   Hulen Thomas M TM   Choudhary Swati S   Theisen Michael M   Singh Susheel K SK   Singh Susheel K SK   Garcia-Senosiain Asier A   Van Oosten Linda L   Pijlman Gorben G   Hierzberger Bettina B   Domeyer Tanja T   Nalewajek Blanka W BW   Strøbæk Anette A   Skrzypczak Magdalena M   Andersson Laura F LF   Buus Søren S   Buus Anette Stryhn AS   Christensen Jan Pravsgaard JP   Dalebout Tim J TJ   Iversen Kasper K   Harritshøj Lene H LH   Mordmüller Benjamin B   Ullum Henrik H   Reinert Line S LS   de Jongh Willem Adriaan WA   Kikkert Marjolein M   Paludan Søren R SR   Theander Thor G TG   Nielsen Morten A MA   Salanti Ali A   Sander Adam F AF  

Nature communications 20210112 1


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  ...[more]

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