Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, uses a surface expressed trimeric spike glycoprotein for cell entry. This trimer is the primary target for neutralizing antibodies making it a key candidate for vaccine development. During t...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-52499-1 |
| _version_ | 1827329283005087744 |
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| author | Eduardo M. Bruch Shaolong Zhu Lisa Szymkowicz Taylor Blake Tara Kiss D. Andrew James Alexey Rak Kartik Narayan Matthew T. Balmer Roman M. Chicz |
| author_facet | Eduardo M. Bruch Shaolong Zhu Lisa Szymkowicz Taylor Blake Tara Kiss D. Andrew James Alexey Rak Kartik Narayan Matthew T. Balmer Roman M. Chicz |
| author_sort | Eduardo M. Bruch |
| collection | DOAJ |
| description | Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, uses a surface expressed trimeric spike glycoprotein for cell entry. This trimer is the primary target for neutralizing antibodies making it a key candidate for vaccine development. During the global pandemic circulating variants of concern (VOC) caused several waves of infection, severe disease, and death. The reduced efficacy of the ancestral trimer-based vaccines against emerging VOC led to the need for booster vaccines. Here we present a detailed characterization of the Sanofi Beta trimer, utilizing cryo-EM for structural elucidation. We investigate the conformational dynamics and stabilizing features using orthogonal SPR, SEC, nanoDSF, and HDX-MS techniques to better understand how this antigen elicits superior broad neutralizing antibodies as a variant booster vaccine. This structural analysis confirms the Beta trimer preference for canonical quaternary structure with two RBD in the up position and the reversible equilibrium between the canonical spike and open trimer conformations. Moreover, this report provides a better understanding of structural differences between spike antigens contributing to differential vaccine efficacy. |
| first_indexed | 2024-03-07T15:30:40Z |
| format | Article |
| id | doaj.art-6498d46d953a4bfcb0fc866354902992 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:30:40Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-6498d46d953a4bfcb0fc8663549029922024-03-05T16:25:40ZengNature PortfolioScientific Reports2045-23222024-01-0114111610.1038/s41598-024-52499-1Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2Eduardo M. Bruch0Shaolong Zhu1Lisa Szymkowicz2Taylor Blake3Tara Kiss4D. Andrew James5Alexey Rak6Kartik Narayan7Matthew T. Balmer8Roman M. Chicz9SanofiSanofiSanofiSanofiSanofiSanofiSanofiSanofiSanofiSanofiAbstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, uses a surface expressed trimeric spike glycoprotein for cell entry. This trimer is the primary target for neutralizing antibodies making it a key candidate for vaccine development. During the global pandemic circulating variants of concern (VOC) caused several waves of infection, severe disease, and death. The reduced efficacy of the ancestral trimer-based vaccines against emerging VOC led to the need for booster vaccines. Here we present a detailed characterization of the Sanofi Beta trimer, utilizing cryo-EM for structural elucidation. We investigate the conformational dynamics and stabilizing features using orthogonal SPR, SEC, nanoDSF, and HDX-MS techniques to better understand how this antigen elicits superior broad neutralizing antibodies as a variant booster vaccine. This structural analysis confirms the Beta trimer preference for canonical quaternary structure with two RBD in the up position and the reversible equilibrium between the canonical spike and open trimer conformations. Moreover, this report provides a better understanding of structural differences between spike antigens contributing to differential vaccine efficacy.https://doi.org/10.1038/s41598-024-52499-1 |
| spellingShingle | Eduardo M. Bruch Shaolong Zhu Lisa Szymkowicz Taylor Blake Tara Kiss D. Andrew James Alexey Rak Kartik Narayan Matthew T. Balmer Roman M. Chicz Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2 Scientific Reports |
| title | Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2 |
| title_full | Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2 |
| title_fullStr | Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2 |
| title_full_unstemmed | Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2 |
| title_short | Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2 |
| title_sort | structural and biochemical rationale for beta variant protein booster vaccine broad cross neutralization of sars cov 2 |
| url | https://doi.org/10.1038/s41598-024-52499-1 |
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