1. Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses.
- Author
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Hills RA, Tan TK, Cohen AA, Keeffe JR, Keeble AH, Gnanapragasam PNP, Storm KN, Rorick AV, West AP Jr, Hill ML, Liu S, Gilbert-Jaramillo J, Afzal M, Napier A, Admans G, James WS, Bjorkman PJ, Townsend AR, and Howarth MR
- Subjects
- Animals, Humans, Vaccination methods, Mice, Nanoparticles chemistry, Female, Antibodies, Neutralizing immunology, SARS-CoV-2 immunology, Antibodies, Viral immunology, Spike Glycoprotein, Coronavirus immunology, Spike Glycoprotein, Coronavirus chemistry, COVID-19 Vaccines immunology, COVID-19 Vaccines chemistry, COVID-19 prevention & control, COVID-19 immunology, COVID-19 virology
- Abstract
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., (© 2024. The Author(s).)
- Published
- 2024
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