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.
【저자키워드】 SARS-CoV-2, Vaccine, spike, rabbit, SpyTag-SpyCatcher, MERS-coronavirus, i301, lumazine synthase, 【초록키워드】 vaccination, Immunity, neutralization, Antibody Response, peptide, virus, MERS-CoV, Spike protein, Particle, Receptor binding domain, Region, pathogen, RBD, viral replication, vaccine candidate, WHO, neutralizing capacity, Critical, platform, Protective, mucosal, Lower respiratory tract, Middle East, viral RBD, respiratory syndrome coronavirus, MERS-CoV infection, heptad repeat, approach, tested, magnitude, producing, displaying, 【제목키워드】 MERS-CoV, Receptor binding domain, protective immune response, Particulate, induce,