Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses

Defending against future pandemics requires vaccine platforms that protect across a range of related pathogens. Nanoscale patterning can be used to address this issue. Here, we produce quartets of linked receptor-binding domains (RBDs) from a panel of SARS-like betacoronaviruses, coupled to a comput...

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Published in:	Nature nanotechnology Vol. 19; no. 8; pp. 1216 - 1223
Main Authors:	Hills, Rory A., Tan, Tiong Kit, Cohen, Alexander A., Keeffe, Jennifer R., Keeble, Anthony H., Gnanapragasam, Priyanthi N. P., Storm, Kaya N., Rorick, Annie V., West, Anthony P., Hill, Michelle L., Liu, Sai, Gilbert-Jaramillo, Javier, Afzal, Madeeha, Napier, Amy, Admans, Gabrielle, James, William S., Bjorkman, Pamela J., Townsend, Alain R., Howarth, Mark R.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01-08-2024 Nature Publishing Group
Subjects:	631/326/596/4130 631/61/350/354 Animals Antibodies Antibodies, Neutralizing - immunology Antibodies, Viral - immunology Binding Chemistry and Materials Science Coronaviruses COVID-19 COVID-19 - immunology COVID-19 - prevention & control COVID-19 - virology COVID-19 Vaccines - chemistry COVID-19 Vaccines - immunology Female Humans Immune response Immune system Materials Science Mice Nanoparticles Nanoparticles - chemistry Nanotechnology Nanotechnology and Microengineering Neutralizing Pandemics Pathogens Receptors SARS-CoV-2 - immunology Severe acute respiratory syndrome coronavirus 2 Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - immunology Vaccination - methods Vaccines Viral diseases
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Summary:	Defending against future pandemics requires vaccine platforms that protect across a range of related pathogens. Nanoscale patterning can be used to address this issue. Here, we produce quartets of linked receptor-binding domains (RBDs) from a panel of SARS-like betacoronaviruses, coupled to a computationally designed nanocage through SpyTag/SpyCatcher links. These Quartet Nanocages, possessing a branched morphology, induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented in the vaccine. Equivalent antibody responses are raised to RBDs close to the nanocage or at the tips of the nanoparticle’s branches. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increase the strength and breadth of an otherwise narrow immune response. A Quartet Nanocage including the Omicron XBB.1.5 ‘Kraken’ RBD induced antibodies with binding to a broad range of sarbecoviruses, as well as neutralizing activity against this variant of concern. Quartet nanocages are a nanomedicine approach with potential to confer heterotypic protection against emergent zoonotic pathogens and facilitate proactive pandemic protection. The ability to vaccinate against multiple related pathogens is a significant advantage. Here, the authors report on quartets of linked receptor-binding domains attached to designed nanocages using SpyTag/SpyCatcher links, demonstrating effective vaccination against similar viruses as well as the variant of concern.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1748-3387 1748-3395 1748-3395
DOI:	10.1038/s41565-024-01655-9