Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV

Emerg Microbes Infect. 2020 Dec;9(1):1080-1091. 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.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Antibody Affinity
  • Antibody Formation*
  • Antigen Presentation*
  • Binding Sites
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / prevention & control
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Vectors
  • HEK293 Cells
  • Humans
  • Immunogenicity, Vaccine
  • Middle East Respiratory Syndrome Coronavirus / immunology
  • Middle East Respiratory Syndrome Coronavirus / physiology
  • Neutralization Tests
  • Protein Binding
  • Protein Domains
  • Rabbits
  • Spike Glycoprotein, Coronavirus / biosynthesis
  • Spike Glycoprotein, Coronavirus / immunology*
  • Viral Vaccines / immunology*
  • Virus Replication

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • Viral Vaccines

Grants and funding

This study was financed by a grant from the IMI-ZAPI (Zoonotic Anticipation and Preparedness Initiative (ZAPI) project; Innovative Medicines Initiative (IMI)) [grant agreement no. 115760], with the assistance and financial support of IMI and the European Commission, and in-kind contributions from European Federation of Pharmaceutical Industries and Associations partners.