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

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,...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2020.1760735
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849731563562991616
author 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
author_facet 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
author_sort Nisreen M. A. Okba
collection DOAJ
description 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.
format Article
id doaj-art-eda04ba2d36a4ed8b9a203977286ddba
institution DOAJ
issn 2222-1751
language English
publishDate 2020-01-01
publisher Taylor & Francis Group
record_format Article
series Emerging Microbes and Infections
spelling doaj-art-eda04ba2d36a4ed8b9a203977286ddba2025-08-20T03:08:31ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-01911080109110.1080/22221751.2020.1760735Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoVNisreen M. A. Okba0Ivy Widjaja1Brenda van Dieren2Andrea Aebischer3Geert van Amerongen4Leon de Waal5Koert J. Stittelaar6Debby Schipper7Byron Martina8Judith M. A. van den Brand9Martin Beer10Berend-Jan Bosch11Bart L. Haagmans12Department of Viroscience, Erasmus Medical Center, Rotterdam, The NetherlandsVirology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The NetherlandsVirology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The NetherlandsInstitute of Diagnostic Virology, Friedrich-Loeffler-Institut, Insel Riems, GermanyViroclinics Biosciences BV, Rotterdam, The NetherlandsViroclinics Biosciences BV, Rotterdam, The NetherlandsViroclinics Biosciences BV, Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Center, Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Center, Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Center, Rotterdam, The NetherlandsInstitute of Diagnostic Virology, Friedrich-Loeffler-Institut, Insel Riems, GermanyVirology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The NetherlandsDepartment of Viroscience, Erasmus Medical Center, Rotterdam, The NetherlandsMiddle 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.https://www.tandfonline.com/doi/10.1080/22221751.2020.1760735VaccineMERS-coronavirusspikei301lumazine synthasespytag-spycatcher
spellingShingle 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
Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV
Emerging Microbes and Infections
Vaccine
MERS-coronavirus
spike
i301
lumazine synthase
spytag-spycatcher
title Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV
title_full Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV
title_fullStr Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV
title_full_unstemmed Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV
title_short Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV
title_sort particulate multivalent presentation of the receptor binding domain induces protective immune responses against mers cov
topic Vaccine
MERS-coronavirus
spike
i301
lumazine synthase
spytag-spycatcher
url https://www.tandfonline.com/doi/10.1080/22221751.2020.1760735
work_keys_str_mv AT nisreenmaokba particulatemultivalentpresentationofthereceptorbindingdomaininducesprotectiveimmuneresponsesagainstmerscov
AT ivywidjaja particulatemultivalentpresentationofthereceptorbindingdomaininducesprotectiveimmuneresponsesagainstmerscov
AT brendavandieren particulatemultivalentpresentationofthereceptorbindingdomaininducesprotectiveimmuneresponsesagainstmerscov
AT andreaaebischer particulatemultivalentpresentationofthereceptorbindingdomaininducesprotectiveimmuneresponsesagainstmerscov
AT geertvanamerongen particulatemultivalentpresentationofthereceptorbindingdomaininducesprotectiveimmuneresponsesagainstmerscov
AT leondewaal particulatemultivalentpresentationofthereceptorbindingdomaininducesprotectiveimmuneresponsesagainstmerscov
AT koertjstittelaar particulatemultivalentpresentationofthereceptorbindingdomaininducesprotectiveimmuneresponsesagainstmerscov
AT debbyschipper particulatemultivalentpresentationofthereceptorbindingdomaininducesprotectiveimmuneresponsesagainstmerscov
AT byronmartina particulatemultivalentpresentationofthereceptorbindingdomaininducesprotectiveimmuneresponsesagainstmerscov
AT judithmavandenbrand particulatemultivalentpresentationofthereceptorbindingdomaininducesprotectiveimmuneresponsesagainstmerscov
AT martinbeer particulatemultivalentpresentationofthereceptorbindingdomaininducesprotectiveimmuneresponsesagainstmerscov
AT berendjanbosch particulatemultivalentpresentationofthereceptorbindingdomaininducesprotectiveimmuneresponsesagainstmerscov
AT bartlhaagmans particulatemultivalentpresentationofthereceptorbindingdomaininducesprotectiveimmuneresponsesagainstmerscov