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

Autor: Hills RA; Department of Biochemistry, University of Oxford, Oxford, UK.; Department of Pharmacology, University of Cambridge, Cambridge, UK., Tan TK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK., Cohen AA; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Keeffe JR; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Keeble AH; Department of Biochemistry, University of Oxford, Oxford, UK.; Department of Pharmacology, University of Cambridge, Cambridge, UK., Gnanapragasam PNP; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Storm KN; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Rorick AV; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., West AP Jr; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Hill ML; James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK., Liu S; James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK., Gilbert-Jaramillo J; James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK., Afzal M; James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK., Napier A; James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK., Admans G; Department of Pharmacology, University of Cambridge, Cambridge, UK., James WS; James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK., Bjorkman PJ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. bjorkman@caltech.edu., Townsend AR; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK. alain.townsend@imm.ox.ac.uk.; Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK. alain.townsend@imm.ox.ac.uk., Howarth MR; Department of Biochemistry, University of Oxford, Oxford, UK. mh2186@cam.ac.uk.; Department of Pharmacology, University of Cambridge, Cambridge, UK. mh2186@cam.ac.uk.
Jazyk: angličtina
Zdroj: Nature nanotechnology [Nat Nanotechnol] 2024 Aug; Vol. 19 (8), pp. 1216-1223. Date of Electronic Publication: 2024 May 06.
DOI: 10.1038/s41565-024-01655-9
Abstrakt: 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).)
Databáze: MEDLINE
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