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, 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:9

Enthalten in:

Emerging microbes & infections - 9(2020), 1 vom: 15. Dez., Seite 1080-1091

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

Antibodies, Neutralizing
Antibodies, Viral
I301
Journal Article
Lumazine synthase
MERS-coronavirus
Rabbit
SARS-CoV-2
Spike
Spike Glycoprotein, Coronavirus
Spytag-spycatcher
Vaccine
Viral Vaccines

Anmerkungen:

Date Completed 02.06.2020

Date Revised 05.03.2024

published: Print

Citation Status MEDLINE

doi:

10.1080/22221751.2020.1760735

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM310518261