tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Ivy Widjaja[SUP] 2 [/SUP], Brenda van Dieren[SUP] 2 [/SUP], Andrea Aebischer[SUP] 3 [/SUP], Geert van Amerongen[SUP] 4 [/SUP], Leon de Waal[SUP] 4 [/SUP], Koert J Stittelaar[SUP] 4 [/SUP], Debby Schipper[SUP] 1 [/SUP], Byron Martina[SUP] 1 [/SUP], Judith M A van den Brand[SUP] 1 [/SUP], Martin Beer[SUP] 3 [/SUP], Berend-Jan Bosch[SUP] 2 [/SUP], Bart L Haagmans[SUP] 1 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], Ivy Widjaja[SUP] 2 [/SUP], Brenda van Dieren[SUP] 2 [/SUP], Andrea Aebischer[SUP] 3 [/SUP], Geert van Amerongen[SUP] 4 [/SUP], Leon de Waal[SUP] 4 [/SUP], Koert J Stittelaar[SUP] 4 [/SUP], Debby Schipper[SUP] 1 [/SUP], Byron Martina[SUP] 1 [/SUP], Judith M A van den Brand[SUP] 1 [/SUP], Martin Beer[SUP] 3 [/SUP], Berend-Jan Bosch[SUP] 2 [/SUP], Bart L Haagmans[SUP] 1 [/SUP]
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.