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Influence of variant-specific mutations, temperature and pH on conformations of a large set of SARS-CoV-2 spike trimer vaccine antigen candidates.
Stuible, Matthew; Schrag, Joseph D; Sheff, Joey; Zoubchenok, Daria; Lord-Dufour, Simon; Cass, Brian; L'Abbé, Denis; Pelletier, Alex; Rossotti, Martin A; Tanha, Jamshid; Gervais, Christian; Maurice, Roger; El Bakkouri, Majida; Acchione, Mauro; Durocher, Yves.
Affiliation
  • Stuible M; Human Health Therapeutics Research Centre, National Research Council Canada, 6100 Royalmount Avenue, Montreal, QC, H4P 2R2, Canada.
  • Schrag JD; Human Health Therapeutics Research Centre, National Research Council Canada, 6100 Royalmount Avenue, Montreal, QC, H4P 2R2, Canada.
  • Sheff J; Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON, Canada.
  • Zoubchenok D; Human Health Therapeutics Research Centre, National Research Council Canada, 6100 Royalmount Avenue, Montreal, QC, H4P 2R2, Canada.
  • Lord-Dufour S; Human Health Therapeutics Research Centre, National Research Council Canada, 6100 Royalmount Avenue, Montreal, QC, H4P 2R2, Canada.
  • Cass B; Human Health Therapeutics Research Centre, National Research Council Canada, 6100 Royalmount Avenue, Montreal, QC, H4P 2R2, Canada.
  • L'Abbé D; Human Health Therapeutics Research Centre, National Research Council Canada, 6100 Royalmount Avenue, Montreal, QC, H4P 2R2, Canada.
  • Pelletier A; Human Health Therapeutics Research Centre, National Research Council Canada, 6100 Royalmount Avenue, Montreal, QC, H4P 2R2, Canada.
  • Rossotti MA; Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON, Canada.
  • Tanha J; Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON, Canada.
  • Gervais C; Human Health Therapeutics Research Centre, National Research Council Canada, 6100 Royalmount Avenue, Montreal, QC, H4P 2R2, Canada.
  • Maurice R; Human Health Therapeutics Research Centre, National Research Council Canada, 6100 Royalmount Avenue, Montreal, QC, H4P 2R2, Canada.
  • El Bakkouri M; Human Health Therapeutics Research Centre, National Research Council Canada, 6100 Royalmount Avenue, Montreal, QC, H4P 2R2, Canada.
  • Acchione M; Human Health Therapeutics Research Centre, National Research Council Canada, 6100 Royalmount Avenue, Montreal, QC, H4P 2R2, Canada.
  • Durocher Y; Human Health Therapeutics Research Centre, National Research Council Canada, 6100 Royalmount Avenue, Montreal, QC, H4P 2R2, Canada. yves.durocher@nrc-cnrc.gc.ca.
Sci Rep ; 13(1): 16498, 2023 10 01.
Article in En | MEDLINE | ID: mdl-37779126
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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: En Journal: Sci Rep Year: 2023 Document type: Article Affiliation country: Canadá Country of publication: Reino Unido

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: En Journal: Sci Rep Year: 2023 Document type: Article Affiliation country: Canadá Country of publication: Reino Unido