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.
|Keywords||i301, lumazine synthase, MERS-coronavirus, rabbit, SARS-CoV-2, spike, spytag-spycatcher, Vaccine|
|Persistent URL||dx.doi.org/10.1080/22221751.2020.1760735, hdl.handle.net/1765/127580|
|Journal||Emerging Microbes and Infections|
Okba, N.M.A, Widjaja, I. (Ivy), van Dieren, B. (Brenda), Aebischer, A. (Andrea), van Amerongen, G, de Waal, L, … 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. doi:10.1080/22221751.2020.1760735