Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV

Nisreen M A Okba; Ivy Widjaja; Brenda van Dieren; Andrea Aebischer; Geert van Amerongen; Leon de Waal; Koert J Stittelaar; Debby Schipper; Byron Martina; Judith M A van den Brand; Martin Beer; Berend-Jan Bosch; Bart L Haagmans

doi:10.1080/22221751.2020.1760735

Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV

Nisreen M A Okba, Ivy Widjaja, Brenda van Dieren, Andrea Aebischer, Geert van Amerongen, Leon de Waal, Koert J Stittelaar, Debby Schipper, Byron Martina, Judith M A van den Brand, Martin Beer, Berend-Jan Bosch, Bart L Haagmans

Virologie

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

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a WHO priority pathogen for which vaccines are urgently needed. Using an immune-focusing approach, we created self-assembling particles multivalently displaying critical regions of the MERS-CoV spike protein ─fusion peptide, heptad repeat 2, and receptor binding domain (RBD) ─ and tested their immunogenicity and protective capacity in rabbits. Using a "plug-and-display" SpyTag/SpyCatcher system, we coupled RBD to lumazine synthase (LS) particles producing multimeric RBD-presenting particles (RBD-LS). RBD-LS vaccination induced antibody responses of high magnitude and quality (avidity, MERS-CoV neutralizing capacity, and mucosal immunity) with cross-clade neutralization. The antibody responses were associated with blocking viral replication and upper and lower respiratory tract protection against MERS-CoV infection in rabbits. This arrayed multivalent presentation of the viral RBD using the antigen-SpyTag/LS-SpyCatcher is a promising MERS-CoV vaccine candidate and this platform may be applied for the rapid development of vaccines against other emerging viruses such as SARS-CoV-2.

Original language	English
Pages (from-to)	1080-1091
Number of pages	12
Journal	Emerging Microbes and Infections
Volume	9
Issue number	1
DOIs	https://doi.org/10.1080/22221751.2020.1760735
Publication status	Published - Dec 2020

Keywords

Animals
Antibodies, Neutralizing/immunology
Antibodies, Viral/immunology
Antibody Affinity
Antibody Formation
Antigen Presentation
Binding Sites
Coronavirus Infections/immunology
Enzyme-Linked Immunosorbent Assay
Female
Genetic Vectors
HEK293 Cells
Humans
Immunogenicity, Vaccine
Middle East Respiratory Syndrome Coronavirus/immunology
Neutralization Tests
Protein Binding
Protein Domains
Rabbits
Spike Glycoprotein, Coronavirus/biosynthesis
Viral Vaccines/immunology
Virus Replication
Vaccine
MERS-coronavirus
spike
i301
lumazine synthase
spytag-spycatcher
SARS-CoV-2

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Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS CoVFinal published version, 2.51 MB

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Okba, N. M. A., Widjaja, I., van Dieren, B., Aebischer, A., van Amerongen, G., de Waal, L., Stittelaar, K. J., Schipper, D., Martina, B., van den Brand, J. M. A., Beer, M., Bosch, B.-J., & Haagmans, B. L. (2020). Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV. Emerging Microbes and Infections, 9(1), 1080-1091. https://doi.org/10.1080/22221751.2020.1760735

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author = "Okba, {Nisreen M A} and Ivy Widjaja and {van Dieren}, Brenda and Andrea Aebischer and {van Amerongen}, Geert and {de Waal}, Leon and Stittelaar, {Koert J} and Debby Schipper and Byron Martina and {van den Brand}, {Judith M A} and Martin Beer and Berend-Jan Bosch and Haagmans, {Bart L}",

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Okba, NMA, Widjaja, I, van Dieren, B, Aebischer, A, van Amerongen, G, de Waal, L, Stittelaar, KJ, Schipper, D, Martina, B, van den Brand, JMA, Beer, M, Bosch, B-J & Haagmans, BL 2020, 'Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV', Emerging Microbes and Infections, vol. 9, no. 1, pp. 1080-1091. https://doi.org/10.1080/22221751.2020.1760735

TY - JOUR

T1 - Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV

AU - Okba, Nisreen M A

AU - Widjaja, Ivy

AU - van Dieren, Brenda

AU - Aebischer, Andrea

AU - van Amerongen, Geert

AU - de Waal, Leon

AU - Stittelaar, Koert J

AU - Schipper, Debby

AU - Martina, Byron

AU - van den Brand, Judith M A

AU - Beer, Martin

AU - Bosch, Berend-Jan

AU - Haagmans, Bart L

PY - 2020/12

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N2 - Middle East respiratory syndrome coronavirus (MERS-CoV) is a WHO priority pathogen for which vaccines are urgently needed. Using an immune-focusing approach, we created self-assembling particles multivalently displaying critical regions of the MERS-CoV spike protein ─fusion peptide, heptad repeat 2, and receptor binding domain (RBD) ─ and tested their immunogenicity and protective capacity in rabbits. Using a "plug-and-display" SpyTag/SpyCatcher system, we coupled RBD to lumazine synthase (LS) particles producing multimeric RBD-presenting particles (RBD-LS). RBD-LS vaccination induced antibody responses of high magnitude and quality (avidity, MERS-CoV neutralizing capacity, and mucosal immunity) with cross-clade neutralization. The antibody responses were associated with blocking viral replication and upper and lower respiratory tract protection against MERS-CoV infection in rabbits. This arrayed multivalent presentation of the viral RBD using the antigen-SpyTag/LS-SpyCatcher is a promising MERS-CoV vaccine candidate and this platform may be applied for the rapid development of vaccines against other emerging viruses such as SARS-CoV-2.

AB - Middle East respiratory syndrome coronavirus (MERS-CoV) is a WHO priority pathogen for which vaccines are urgently needed. Using an immune-focusing approach, we created self-assembling particles multivalently displaying critical regions of the MERS-CoV spike protein ─fusion peptide, heptad repeat 2, and receptor binding domain (RBD) ─ and tested their immunogenicity and protective capacity in rabbits. Using a "plug-and-display" SpyTag/SpyCatcher system, we coupled RBD to lumazine synthase (LS) particles producing multimeric RBD-presenting particles (RBD-LS). RBD-LS vaccination induced antibody responses of high magnitude and quality (avidity, MERS-CoV neutralizing capacity, and mucosal immunity) with cross-clade neutralization. The antibody responses were associated with blocking viral replication and upper and lower respiratory tract protection against MERS-CoV infection in rabbits. This arrayed multivalent presentation of the viral RBD using the antigen-SpyTag/LS-SpyCatcher is a promising MERS-CoV vaccine candidate and this platform may be applied for the rapid development of vaccines against other emerging viruses such as SARS-CoV-2.

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KW - Antibodies, Neutralizing/immunology

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KW - Antibody Affinity

KW - Antibody Formation

KW - Antigen Presentation

KW - Binding Sites

KW - Coronavirus Infections/immunology

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Genetic Vectors

KW - HEK293 Cells

KW - Humans

KW - Immunogenicity, Vaccine

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KW - Neutralization Tests

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KW - Spike Glycoprotein, Coronavirus/biosynthesis

KW - Viral Vaccines/immunology

KW - Virus Replication

KW - Vaccine

KW - MERS-coronavirus

KW - spike

KW - i301

KW - lumazine synthase

KW - spytag-spycatcher

KW - SARS-CoV-2

U2 - 10.1080/22221751.2020.1760735

DO - 10.1080/22221751.2020.1760735

M3 - Article

C2 - 32471334

SN - 2222-1751

VL - 9

SP - 1080

EP - 1091

JO - Emerging Microbes and Infections

JF - Emerging Microbes and Infections

IS - 1

ER -

Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV

Abstract

Keywords

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