Identification of an Optimized Receptor-Binding Domain Subunit Vaccine against SARS-CoV-2.

Autor:	Yu H; British Columbia Centre for Disease Control, University of British Columbia, Vancouver, British Columbia, Canada., Worrall LJ; Department of Biochemistry and Molecular Biology, Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada., Berger T; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Petric M; British Columbia Centre for Disease Control, University of British Columbia, Vancouver, British Columbia, Canada., Lin BH; Department of Biochemistry and Molecular Biology, Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada., Vuckovic M; Department of Biochemistry and Molecular Biology, Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada., Robb CS; Department of Biochemistry and Molecular Biology, Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada., Le Q; Department of Biochemistry and Molecular Biology, Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada., Kenward C; Department of Biochemistry and Molecular Biology, Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada., Dai C; British Columbia Centre for Disease Control, University of British Columbia, Vancouver, British Columbia, Canada., Wakeham A; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Liu S; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Snow B; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Tobin C; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Budylowski P; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.; Toronto High Containment Facility, University of Toronto, Toronto, Ontario, Canada., Guvenc F; Toronto High Containment Facility, University of Toronto, Toronto, Ontario, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada., You-Ten A; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Haight J; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Silvester J; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Singh RP; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Ahn SK; Toronto High Containment Facility, University of Toronto, Toronto, Ontario, Canada., Sultana A; Toronto High Containment Facility, University of Toronto, Toronto, Ontario, Canada., Poon B; Toronto High Containment Facility, University of Toronto, Toronto, Ontario, Canada., Lam J; Toronto High Containment Facility, University of Toronto, Toronto, Ontario, Canada., Christie-Holmes N; Emerging and Pandemic Infections Consortium, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada., Ostrowski M; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada., Gray-Owen SD; Toronto High Containment Facility, University of Toronto, Toronto, Ontario, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada., Kubli S; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.; Treadwell Therapeutics, Toronto, Ontario, Canada., Mak T; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.; Centre for Oncology and Immunology, Hong Kong Science Park, Hong Kong SAR, China.; Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Strynadka NCJ; Department of Biochemistry and Molecular Biology, Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada., Brunham RC; British Columbia Centre for Disease Control, University of British Columbia, Vancouver, British Columbia, Canada.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2023 Sep 15; Vol. 211 (6), pp. 981-993.
DOI:	10.4049/jimmunol.2300282
Abstrakt:	Current vaccine efforts to combat SARS-CoV-2 are focused on the whole spike protein administered as mRNA, viral vector, or protein subunit. However, the SARS-CoV-2 receptor-binding domain (RBD) is the immunodominant portion of the spike protein, accounting for 90% of serum neutralizing activity. In this study, we constructed several versions of RBD and together with aluminum hydroxide or DDA (dimethyldioctadecylammonium bromide)/TDB (d-(+)-trehalose 6,6'-dibehenate) adjuvant evaluated immunogenicity in mice. We generated human angiotensin-converting enzyme 2 knock-in mice to evaluate vaccine efficacy in vivo following viral challenge. We found that 1) subdomain (SD)1 was essential for the RBD to elicit maximal immunogenicity; 2) RBDSD1 produced in mammalian HEK cells elicited better immunogenicity than did protein produced in insect or yeast cells; 3) RBDSD1 combined with the CD4 Th1 adjuvant DDA/TDB produced higher neutralizing Ab responses and stronger CD4 T cell responses than did aluminum hydroxide; 4) addition of monomeric human Fc receptor to RBDSD1 (RBDSD1Fc) significantly enhanced immunogenicity and neutralizing Ab titers; 5) the Beta version of RBDSD1Fc provided a broad range of cross-neutralization to multiple antigenic variants of concern, including Omicron; and 6) the Beta version of RBDSD1Fc with DDA/TDB provided complete protection against virus challenge in the knock-in mouse model. Thus, we have identified an optimized RBD-based subunit vaccine suitable for clinical trials. (Copyright © 2023 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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