Structure of a vaccine candidate Much effort is being targeted at developing vaccines that will provide protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A trimeric spike protein that decorates the virus is a primary target of the host immune system and the focus of vaccine development. Bangaru et al. present the structure of a leading vaccine candidate: a full-length spike protein with some modifications aimed at enhancing stability that is formulated in polysorbate 80 detergent. The study confirms that the full-length immunogen is in a stable prefusion conformation and provides a basis for understanding immune responses to the vaccine. Science, this issue p. 1089 Cryo-EM and glycan analysis of a leading SARS-CoV-2 subunit vaccine candidate reveals a stable prefusion conformation of the spike immunogen. Vaccine efforts to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, are focused on SARS-CoV-2 spike glycoprotein, the primary target for neutralizing antibodies. We performed cryo–election microscopy and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax, which is based on a full-length spike protein formulated in polysorbate 80 detergent. Our studies reveal a stable prefusion conformation of the spike immunogen with slight differences in the S1 subunit compared with published spike ectodomain structures. We also observed interactions between the spike trimers, allowing formation of higher-order spike complexes. This study confirms the structural integrity of the full-length spike protein immunogen and provides a basis for interpreting immune responses to this multivalent nanoparticle immunogen.

中文翻译：

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对先进候选疫苗的全长 SARS-CoV-2 刺突蛋白进行结构分析


候选疫苗的结构 人们正在努力开发能够预防严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的疫苗。修饰病毒的三聚体刺突蛋白是宿主免疫系统的主要目标，也是疫苗开发的重点。班加鲁等人。展示了一种主要候选疫苗的结构：一种全长刺突蛋白，经过一些修饰，旨在增强稳定性，配制在聚山梨酯 80 去污剂中。该研究证实全长免疫原处于稳定的预融合构象，并为了解疫苗的免疫反应提供了基础。科学，本期第 14 页。 1089 对领先的 SARS-CoV-2 亚单位候选疫苗进行冷冻电镜和聚糖分析，揭示了刺突免疫原的稳定预融合构象。对抗严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的疫苗工作重点关注 SARS-CoV-2 刺突糖蛋白，该蛋白是当前 2019 年冠状病毒病 (COVID-19) 大流行的主要靶标。中和抗体。我们对 Novavax 的一种主要亚单位候选疫苗进行了冷冻电子显微镜和位点特异性聚糖分析，该候选疫苗基于用聚山梨醇酯 80 洗涤剂配制的全长刺突蛋白。我们的研究揭示了刺突免疫原的稳定预融合构象，与已发表的刺突胞外域结构相比，S1 亚基略有差异。我们还观察到尖峰三聚体之间的相互作用，从而形成更高阶的尖峰复合物。这项研究证实了全长刺突蛋白免疫原的结构完整性，并为解释对这种多价纳米颗粒免疫原的免疫反应提供了基础。