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

Hills RA., Kit Tan T., 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.

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.

DOI

10.1101/2023.02.24.529520

Type

Journal article

Publication Date

2023-02-24T00:00:00+00:00

Keywords

Covid-19, bioconjugation, nanobiotechnology, outbreak pathogens, synthetic biology, zoonotic

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