Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity
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Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity. / Fougeroux, Cyrielle; Goksøyr, Louise; Idorn, Manja; Soroka, Vladislav; Myeni, Sebenzile K; Dagil, Robert; Janitzek, Christoph M; Søgaard, Max; Aves, Kara-Lee; Horsted, Emma W; Erdogan, 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.
I: Nature Communications, Bind 12, Nr. 1, 2021, s. 324.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 255401135