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 Citationer (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.

Originalsprog	Engelsk
Artikelnummer	324
Tidsskrift	Nature Communications
Vol/bind	12
Udgave nummer	1
Sider (fra-til)	324
DOI	https://doi.org/10.1038/s41467-020-20251-8
Status	Udgivet - dec. 2021

Adgang til dokumentet

10.1038/s41467-020-20251-8

Andre filer og links

Link to publication in Scopus

Citationsformater

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. Artikel 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, bind 12, nr. 1, 324, s. 324. https://doi.org/10.1038/s41467-020-20251-8

@article{1f13f08604b6400698eb41f156da134d,

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.",

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",

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 Kara-Lee Aves 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}",

year = "2021",

month = dec,

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

language = "English",

volume = "12",

pages = "324",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

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 - 2021/12

Y1 - 2021/12

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.

KW - Angiotensin-Converting Enzyme 2

KW - Animals

KW - Antibodies, Neutralizing/immunology

KW - Antibodies, Viral/immunology

KW - COVID-19/prevention & control

KW - COVID-19 Vaccines/immunology

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

KW - Serologic Tests

KW - Spike Glycoprotein, Coronavirus/immunology

UR - http://www.scopus.com/inward/record.url?scp=85099203595&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-20251-8

DO - 10.1038/s41467-020-20251-8

M3 - Journal article

C2 - 33436573

SN - 2041-1723

VL - 12

SP - 324

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

Adgang til dokumentet

Andre filer og links

Fingeraftryk

Citationsformater