8TYL

Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2

8TYL の概要

• エントリーDOI: 10.2210/pdb8tyl/pdb
• EMDBエントリー: 41725
• 分子名称: Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• 機能のキーワード: spike, trimer, surface, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 421264.62

構造登録者

Bruch, E.M.,Rak, A. (登録日: 2023-08-25, 公開日: 2024-02-07, 最終更新日: 2024-11-20)

主引用文献

Bruch, E.M.,Zhu, S.,Szymkowicz, L.,Blake, T.,Kiss, T.,James, D.A.,Rak, A.,Narayan, K.,Balmer, M.T.,Chicz, R.M.
Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2.
Sci Rep, 14:2038-2038, 2024

PubMed 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.

PubMed: 38263191
DOI: 10.1038/s41598-024-52499-1

実験手法

ELECTRON MICROSCOPY (2.85 Å)