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一个广泛可通用的稳定策略,用于sarbecovirus融合机器疫苗

Jimin Lee¹, Cameron Stewart¹, Alexandra Schäfer²

¹Department of Biochemistry, University of Washington, Seattle, Washington, USA.

Nature communications

|June 29, 2024

概括

针对SARS-CoV-2保存的S2亚单元的新疫苗显示出对进化变异的承诺. 这种方法引起了广泛的抗体反应,并防止感染,为未来的冠状病毒疫苗提供了潜在的战略.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
疫苗开发疫苗开发

背景情况:

SARS-CoV-2 的演变改变了尖端蛋白的抗原性,降低了疫苗和抗体治疗的有效性.
尖端 (S) 蛋白的受体结合域 (RBD) 和N端域 (NTD) 是高度可变的,并且是当前疫苗的目标.
S2子单元是尖端蛋白的保存,转移稳定的聚变机械组件.

研究的目的:

开发一种疫苗策略,将抗体反应的重点放在SARS-CoV-2保存的S2亚单元上.
创建一个稳定,预注射S2三元体候选疫苗,具有原生结构和抗原性.
评估S2专注策略对其他沙贝科病毒的通用性.

主要方法:

在SARS-CoV-2 S2 trimers的工程预注射稳定.
稳定S2修剪器的高产重组生产.
使用SARS-CoV-1和PRD-0038 S2子单位测试的概括性.
用稳定型SARS-CoV-2 S2三分体疫苗接种疫苗的小鼠.
挑战用XBB.1.5变种接种疫苗的小鼠.

主要成果:

在复合SARS-CoV-2 S2三分体中实现了原生结构和抗原性.
证明了S2稳定策略对其他sarbecoviruses的广泛通用性.
通过S2三分体免疫,产生了广泛反应的萨尔贝科病毒抗体.
实现了与武汉-胡-1和XBB.1.5变体相比较的中和抗体标位.
接种疫苗的小鼠在XBB.1.5挑战时显示出对体重减轻和疾病的保护.

结论:

在融合前稳定S2三元体代表了针对SARS-CoV-2和相关的萨尔贝科病毒的可行的疫苗平台.
专注于保存的S2亚单元可以克服病毒进化所带来的抗原性挑战.
这一战略为开发基于融合机器的广泛保护性萨尔贝科病毒疫苗提供了原则证明.

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