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

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

doi:10.1038/s41467-020-20251-8

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

Cyrielle Fougeroux, Louise Goksøyr, Manja Idorn, Vladislav Soroka, Sebenzile K. Myeni, Robert Dagil, Christoph M. Janitzek, Max Søgaard, Kara Lee Aves, Emma W. Horsted, Sayit Mahmut Erdoğan, Tobias Gustavsson, Jerzy Dorosz, Stine Clemmensen, Laurits Fredsgaard, Susan Thrane, Elena E. Vidal-Calvo, Paul Khalifé, Thomas M. Hulen, Swati ChoudharyMichael Theisen, Susheel K. Singh, Asier Garcia-Senosiain, Linda Van Oosten, Gorben Pijlman, Bettina Hierzberger, Tanja Domeyer, Blanka W. Nalewajek, Anette Strøbæk, Magdalena Skrzypczak, Laura F. Andersson, Søren Buus, Anette Stryhn Buus, Jan Pravsgaard Christensen, Tim J. Dalebout, Kasper Iversen, Lene H. Harritshøj, Benjamin Mordmüller, Henrik Ullum, Line S. Reinert, Willem Adriaan de Jongh, Marjolein Kikkert, Søren R. Paludan, Thor G. Theander, Morten A. Nielsen^*, Ali Salanti, Adam F. Sander^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

54 Citations (Scopus)

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.

Original language	English
Article number	324
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-20251-8
Publication status	Published - 12 Jan 2021

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Prevent-nCoV: Prevention of SARS-CoV-2 infection through development and clinical testing of a novel Virus Like Particle (VLP) vaccine
1/04/20 → 30/06/22
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Fougeroux, C., Goksøyr, L., Idorn, M., Soroka, V., Myeni, S. K., Dagil, R., Janitzek, C. M., Søgaard, M., Aves, K. L., Horsted, E. W., Erdoğan, S. M., Gustavsson, T., Dorosz, J., Clemmensen, S., Fredsgaard, L., Thrane, S., Vidal-Calvo, E. E., Khalifé, P., Hulen, T. M., ... Sander, A. F. (2021). Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity. Nature Communications, 12(1), [324]. https://doi.org/10.1038/s41467-020-20251-8

@article{56c674fd6d434d84a385a1a958866f69,

title = "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.",

author = "Cyrielle Fougeroux and Louise Goks{\o}yr and Manja Idorn and Vladislav Soroka and Myeni, {Sebenzile K.} and Robert Dagil and Janitzek, {Christoph M.} and Max S{\o}gaard and Aves, {Kara Lee} and Horsted, {Emma W.} and Erdoğan, {Sayit Mahmut} and Tobias Gustavsson and Jerzy Dorosz and Stine Clemmensen and Laurits Fredsgaard and Susan Thrane and Vidal-Calvo, {Elena E.} and Paul Khalif{\'e} and Hulen, {Thomas M.} and Swati Choudhary and Michael Theisen and Singh, {Susheel K.} and Asier Garcia-Senosiain and {Van Oosten}, Linda and Gorben Pijlman and Bettina Hierzberger and Tanja Domeyer and Nalewajek, {Blanka W.} and Anette Str{\o}b{\ae}k and Magdalena Skrzypczak and Andersson, {Laura F.} and S{\o}ren Buus and Buus, {Anette Stryhn} and Christensen, {Jan Pravsgaard} and Dalebout, {Tim J.} and Kasper Iversen and Harritsh{\o}j, {Lene H.} and Benjamin Mordm{\"u}ller and Henrik Ullum and Reinert, {Line S.} and {de Jongh}, {Willem Adriaan} and Marjolein Kikkert and Paludan, {S{\o}ren R.} and Theander, {Thor G.} and Nielsen, {Morten A.} and Ali Salanti and Sander, {Adam F.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = jan,

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doi = "10.1038/s41467-020-20251-8",

language = "English",

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Fougeroux, C, Goksøyr, L, Idorn, M, Soroka, V, Myeni, SK, Dagil, R, Janitzek, CM, Søgaard, M, Aves, KL, Horsted, EW, Erdoğan, SM, Gustavsson, T, Dorosz, J, Clemmensen, S, Fredsgaard, L, Thrane, S, Vidal-Calvo, EE, Khalifé, P, Hulen, TM, Choudhary, S, Theisen, M, Singh, SK, Garcia-Senosiain, A, Van Oosten, L , Pijlman, G, Hierzberger, B, Domeyer, T, Nalewajek, BW, Strøbæk, A, Skrzypczak, M, Andersson, LF, Buus, S, Buus, AS, Christensen, JP, Dalebout, TJ, Iversen, K, Harritshøj, LH, Mordmüller, B, Ullum, H, Reinert, LS, de Jongh, WA, Kikkert, M, Paludan, SR, Theander, TG, Nielsen, MA, Salanti, A & Sander, AF 2021, 'Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity', Nature Communications, vol. 12, no. 1, 324. https://doi.org/10.1038/s41467-020-20251-8

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 - Erdoğan, 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 - 2021/1/12

Y1 - 2021/1/12

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 - Article

C2 - 33436573

AN - SCOPUS:85099203595

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 324

ER -

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

Abstract

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Prevent-nCoV: Prevention of SARS-CoV-2 infection through development and clinical testing of a novel Virus Like Particle (VLP) vaccine

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