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

Author:

Fougeroux CyrielleORCID,Goksøyr LouiseORCID,Idorn ManjaORCID,Soroka Vladislav,Myeni Sebenzile K.,Dagil RobertORCID,Janitzek Christoph M.,Søgaard Max,Aves Kara-LeeORCID,Horsted Emma W.,Erdoğan Sayit MahmutORCID,Gustavsson Tobias,Dorosz Jerzy,Clemmensen Stine,Fredsgaard LauritsORCID,Thrane Susan,Vidal-Calvo Elena E.ORCID,Khalifé PaulORCID,Hulen Thomas M.ORCID,Choudhary Swati,Theisen Michael,Singh Susheel K.,Garcia-Senosiain Asier,Van Oosten Linda,Pijlman GorbenORCID,Hierzberger BettinaORCID,Domeyer TanjaORCID,Nalewajek Blanka W.,Strøbæk AnetteORCID,Skrzypczak MagdalenaORCID,Andersson Laura F.,Buus SørenORCID,Buus Anette Stryhn,Christensen Jan PravsgaardORCID,Dalebout Tim J.,Iversen Kasper,Harritshøj Lene H.,Mordmüller BenjaminORCID,Ullum Henrik,Reinert Line S.ORCID,de Jongh Willem Adriaan,Kikkert MarjoleinORCID,Paludan Søren R.ORCID,Theander Thor G.,Nielsen Morten A.ORCID,Salanti Ali,Sander Adam F.ORCID

Abstract

AbstractThe 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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