TY - JOUR
T1 - Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity
AU - Fougeroux, Cyrielle
AU - Goksøyr, Louise
AU - Idorn, Manja
AU - Soroka, Vladislav
AU - Myeni, Sebenzile K
AU - Dagil, Robert
AU - Janitzek, Christoph M
AU - Søgaard, Max
AU - Aves, Kara-Lee
AU - Horsted, Emma W
AU - Erdogan, Sayit Mahmut
AU - Gustavsson, Tobias
AU - Dorosz, Jerzy
AU - Clemmensen, Stine
AU - Fredsgaard, Laurits
AU - Thrane, Susan
AU - Vidal-Calvo, Elena E
AU - Khalifé, Paul
AU - Hulen, Thomas M
AU - Choudhary, Swati
AU - Theisen, Michael
AU - Singh, Susheel K
AU - Garcia-Senosiain, Asier
AU - Van Oosten, Linda
AU - Pijlman, Gorben
AU - Hierzberger, Bettina
AU - Domeyer, Tanja
AU - Nalewajek, Blanka W
AU - Strøbæk, Anette
AU - Skrzypczak, Magdalena
AU - Andersson, Laura F
AU - Buus, Søren
AU - Buus, Anette Stryhn
AU - Christensen, Jan Pravsgaard
AU - Dalebout, Tim J
AU - Iversen, Kasper
AU - Harritshøj, Lene H
AU - Mordmüller, Benjamin
AU - Ullum, Henrik
AU - Reinert, Line S
AU - de Jongh, Willem Adriaan
AU - Kikkert, Marjolein
AU - Paludan, Søren R
AU - Theander, Thor G
AU - Nielsen, Morten A
AU - Salanti, Ali
AU - Sander, Adam F
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-020-20251-8
DO - 10.1038/s41467-020-20251-8
M3 - Journal article
C2 - 33436573
VL - 12
SP - 324
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
ER -