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| DOI | Resolve DOI: https://doi.org/10.1038/s41598-023-43661-2 |
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| Author | Search for: Stuible, Matthew1; Search for: Schrag, Joseph D.1; Search for: Sheff, Joey1; Search for: Zoubchenok, Daria1; Search for: Lord-Dufour, Simon1; Search for: Cass, Brian1; Search for: L'Abbé, Denis2; Search for: Pelletier, Alex1; Search for: Rossotti, Martin A.1; Search for: Tanha, Jamshid1; Search for: Gervais, Christian1; Search for: Maurice, Roger1; Search for: El Bakkouri, Majida1; Search for: Acchione, Mauro1; Search for: Durocher, Yves1 |
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| Affiliation | - National Research Council of Canada. Human Health Therapeutics
- National Research Council of Canada. Medical Devices
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| Format | Text, Article |
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| Abstract | SARS-CoV-2 subunit vaccines continue to be the focus of intense clinical development worldwide. Protein antigens in these vaccines most commonly consist of the spike ectodomain fused to a heterologous trimerization sequence, designed to mimic the compact, prefusion conformation of the spike on the virus surface. Since 2020, we have produced dozens of such constructs in CHO cells, consisting of spike variants with different mutations fused to different trimerization sequences. This set of constructs displayed notable conformational heterogeneity, with two distinct trimer species consistently detected by analytical size exclusion chromatography. A recent report showed that spike ectodomain fusion constructs can adopt an alternative trimer conformation consisting of loosely associated ectodomain protomers. Here, we applied multiple biophysical and immunological techniques to demonstrate that this alternative conformation is formed to a significant extent by several SARS-CoV-2 variant spike proteins. We have also examined the influence of temperature and pH, which can induce inter-conversion of the two forms. The substantial structural differences between these trimer types may impact their performance as vaccine antigens. |
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| Publication date | 2023-10-01 |
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| Publisher | Nature Research |
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| Licence | |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 1ae2dc43-f1b8-4d88-9b7a-b9985c2bbe4d |
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| Record created | 2024-06-05 |
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| Record modified | 2024-06-05 |
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