Emerg Microbes Infect Particulate Multivalent Presentation of the Receptor Binding Domain Induces Protective Immune Responses Against MERS-CoV

[tetano]

Emerg Microbes Infect


. 2020 Dec;9(1):1080-1091.
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 ¹ , Ivy Widjaja ² , Brenda van Dieren ² , Andrea Aebischer ³ , Geert van Amerongen ⁴ , Leon de Waal ⁴ , Koert J Stittelaar ⁴ , Debby Schipper ¹ , Byron Martina ¹ , Judith M A van den Brand ¹ , Martin Beer ³ , Berend-Jan Bosch ² , Bart L Haagmans ¹



Affiliations

• PMID: 32471334
• DOI: 10.1080/22221751.2020.1760735

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.

Keywords: MERS-coronavirus; SARS-CoV-2; Vaccine; i301; lumazine synthase; rabbit; spike; spytag-spycatcher.