Identification of an Optimized Receptor-Binding Domain Subunit Vaccine against SARS-CoV-2 Article Swipe
Hong Yu
,
L.J. Worrall
,
Thorsten Berger
,
Martin Petric
,
Bryan H. Lin
,
M. Vuckovic
,
Craig S. Robb
,
Quan Le
,
Calem Kenward
,
Chuanbin Dai
,
Andrew Wakeham
,
Shaofeng Liu
,
Bryan E. Snow
,
Chantal Tobin
,
Patrick Budylowski
,
Furkan Guvenc
,
Annick You-Ten
,
Jillian Haight
,
Jennifer Silvester
,
Rashim Pal Singh
,
Sang Kyun Ahn
,
Azmiri Sultana
,
Betty Poon
,
Jessica Lam
,
Natasha Christie-Holmes
,
Mario Ostrowski
,
Scott D. Gray‐Owen
,
Shawn P. Kubli
,
Tak W. Mak
,
N.C.J. Strynadka
,
Robert C. Brunham
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.4049/jimmunol.2300282
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.4049/jimmunol.2300282
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.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.4049/jimmunol.2300282
- https://journals.aai.org/jimmunol/article-pdf/211/6/981/1639333/ji2300282.pdf
- OA Status
- bronze
- Cited By
- 2
- References
- 38
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4385263897
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4385263897Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.4049/jimmunol.2300282Digital Object Identifier
- Title
-
Identification of an Optimized Receptor-Binding Domain Subunit Vaccine against SARS-CoV-2Work title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-07-26Full publication date if available
- Authors
-
Hong Yu, L.J. Worrall, Thorsten Berger, Martin Petric, Bryan H. Lin, M. Vuckovic, Craig S. Robb, Quan Le, Calem Kenward, Chuanbin Dai, Andrew Wakeham, Shaofeng Liu, Bryan E. Snow, Chantal Tobin, Patrick Budylowski, Furkan Guvenc, Annick You-Ten, Jillian Haight, Jennifer Silvester, Rashim Pal Singh, Sang Kyun Ahn, Azmiri Sultana, Betty Poon, Jessica Lam, Natasha Christie-Holmes, Mario Ostrowski, Scott D. Gray‐Owen, Shawn P. Kubli, Tak W. Mak, N.C.J. Strynadka, Robert C. BrunhamList of authors in order
- Landing page
-
https://doi.org/10.4049/jimmunol.2300282Publisher landing page
- PDF URL
-
https://journals.aai.org/jimmunol/article-pdf/211/6/981/1639333/ji2300282.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
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https://journals.aai.org/jimmunol/article-pdf/211/6/981/1639333/ji2300282.pdfDirect OA link when available
- Concepts
-
Immunogenicity, Adjuvant, Virology, Neutralizing antibody, Antigenicity, Protein subunit, Biology, Neutralization, Molecular biology, Antigen, Chemistry, Virus, Immunology, Biochemistry, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
2Total citation count in OpenAlex
- Citations by year (recent)
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2024: 1, 2023: 1Per-year citation counts (last 5 years)
- References (count)
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38Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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