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

101 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
Pages (from-to)	324
DOIs	https://doi.org/10.1038/s41467-020-20251-8
Publication status	Published - Dec 2021

Keywords

Angiotensin-Converting Enzyme 2
Animals
Antibodies, Neutralizing/immunology
Antibodies, Viral/immunology
COVID-19/prevention & control
COVID-19 Vaccines/immunology
Capsid/immunology
Female
Humans
Immunogenicity, Vaccine
Kinetics
Mice
Mice, Inbred BALB C
Protein Binding/genetics
Recombinant Proteins/genetics
SARS-CoV-2/immunology
Serologic Tests
Spike Glycoprotein, Coronavirus/immunology

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10.1038/s41467-020-20251-8

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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. Article 324. https://doi.org/10.1038/s41467-020-20251-8

Fougeroux, C, Goksøyr, L, Idorn, M, Soroka, V, Myeni, SK, Dagil, R, Janitzek, CM, Søgaard, M, Aves, K-L, 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, pp. 324. https://doi.org/10.1038/s41467-020-20251-8

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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.",

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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

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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.

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KW - Capsid/immunology

KW - Female

KW - Humans

KW - Immunogenicity, Vaccine

KW - Kinetics

KW - Mice

KW - Mice, Inbred BALB C

KW - Protein Binding/genetics

KW - Recombinant Proteins/genetics

KW - SARS-CoV-2/immunology

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JO - Nature Communications

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ER -

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

Abstract

Keywords

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