Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV
Publication date
2020-12
Authors
Okba, Nisreen M A
Widjaja, Ivy
van Dieren, Brenda
Aebischer, Andrea
van Amerongen, Geert
de Waal, Leon
Stittelaar, Koert J
Schipper, Debby
Martina, Byron
van den Brand, Judith
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Article
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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
Animals, Antibodies, Neutralizing/immunology, Antibodies, Viral/immunology, Antibody Affinity, Antibody Formation, Antigen Presentation, Binding Sites, Coronavirus Infections/immunology, Enzyme-Linked Immunosorbent Assay, Female, Genetic Vectors, HEK293 Cells, Humans, Immunogenicity, Vaccine, Middle East Respiratory Syndrome Coronavirus/immunology, Neutralization Tests, Protein Binding, Protein Domains, Rabbits, Spike Glycoprotein, Coronavirus/biosynthesis, Viral Vaccines/immunology, Virus Replication, Vaccine, MERS-coronavirus, spike, i301, lumazine synthase, spytag-spycatcher, SARS-CoV-2, SDG 3 - Good Health and Well-being
Citation
Okba, N M A, Widjaja, I, van Dieren, B, Aebischer, A, van Amerongen, G, de Waal, L, Stittelaar, K J, Schipper, D, Martina, B, van den Brand, J M A, Beer, M, Bosch, B-J & Haagmans, B L 2020, 'Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV', Emerging Microbes and Infections, vol. 9, no. 1, pp. 1080-1091. https://doi.org/10.1080/22221751.2020.1760735