A platform technology for generating subunit vaccines against diverse viral pathogens.

Autor:	Young A; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.; The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia., Isaacs A; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia., Scott CAP; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia., Modhiran N; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.; The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia., McMillan CLD; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia., Cheung STM; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia., Barr J; CSIRO, Health and Biosecurity, Australian Centre for Disease Preparedness, Geelong, VIC, Australia., Marsh G; CSIRO, Health and Biosecurity, Australian Centre for Disease Preparedness, Geelong, VIC, Australia., Thakur N; The Pirbright Institute, Woking, United Kingdom.; Oxford Vaccine Group, Department of Paediatrics, Medical Sciences Division, University of Oxford, Oxford, United Kingdom., Bailey D; The Pirbright Institute, Woking, United Kingdom., Li KSM; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China., Luk HKH; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China., Kok KH; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China., Lau SKP; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China., Woo PCY; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China., Furuyama W; Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States., Marzi A; Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States., Young PR; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.; The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.; Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, QLD, Australia., Chappell KJ; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.; The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.; Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, QLD, Australia., Watterson D; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.; The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.; Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, QLD, Australia.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Aug 18; Vol. 13, pp. 963023. Date of Electronic Publication: 2022 Aug 18 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.963023
Abstrakt:	The COVID-19 pandemic response has shown how vaccine platform technologies can be used to rapidly and effectively counteract a novel emerging infectious disease. The speed of development for mRNA and vector-based vaccines outpaced those of subunit vaccines, however, subunit vaccines can offer advantages in terms of safety and stability. Here we describe a subunit vaccine platform technology, the molecular clamp, in application to four viruses from divergent taxonomic families: Middle Eastern respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), Lassa virus (LASV) and Nipah virus (NiV). The clamp streamlines subunit antigen production by both stabilising the immunologically important prefusion epitopes of trimeric viral fusion proteins while enabling purification without target-specific reagents by acting as an affinity tag. Conformations for each viral antigen were confirmed by monoclonal antibody binding, size exclusion chromatography and electron microscopy. Notably, all four antigens tested remained stable over four weeks of incubation at 40°C. Of the four vaccines tested, a neutralising immune response was stimulated by clamp stabilised MERS-CoV spike, EBOV glycoprotein and NiV fusion protein. Only the clamp stabilised LASV glycoprotein precursor failed to elicit virus neutralising antibodies. MERS-CoV and EBOV vaccine candidates were both tested in animal models and found to provide protection against viral challenge. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Young, Isaacs, Scott, Modhiran, McMillan, Cheung, Barr, Marsh, Thakur, Bailey, Li, Luk, Kok, Lau, Woo, Furuyama, Marzi, Young, Chappell and Watterson.)
Databáze:	MEDLINE
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