Multiviral Quartet Nanocages Elicit Broad Anti-Coronavirus Responses for Proactive Vaccinology.

Hills RA., Tan TK., Cohen AA., Keeffe JR., Keeble AH., Gnanapragasam PNP., Storm KN., Hill ML., Liu S., Gilbert-Jaramillo J., Afzal M., Napier A., James WS., Bjorkman PJ., Townsend AR., Howarth M.

UNLABELLED: Defending against future pandemics may require vaccine platforms that protect across a range of related pathogens. The presentation of multiple receptor-binding domains (RBDs) from evolutionarily-related viruses on a nanoparticle scaffold elicits a strong antibody response to conserved regions. Here we produce quartets of tandemly-linked RBDs from SARS-like betacoronaviruses coupled to the mi3 nanocage through a SpyTag/SpyCatcher spontaneous reaction. These Quartet Nanocages induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented on the vaccine. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increased the strength and breadth of an otherwise narrow immune response. Quartet Nanocages are a strategy with potential to confer heterotypic protection against emergent zoonotic coronavirus pathogens and facilitate proactive pandemic protection. ONE SENTENCE SUMMARY: A vaccine candidate with polyprotein antigens displayed on nanocages induces neutralizing antibodies to multiple SARS-like coronaviruses.

DOI

10.1101/2023.02.24.529520

Type

Journal article

Journal

bioRxiv

Publication Date

24/02/2023

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