开发一种热稳定且广泛中和的泛沙尔贝病毒疫苗候选剂
Simran Srivastava1, Sahil Kumar2, Suman Mishra1
1Molecular Biophysics Unit, Indian Institute of Science, Bengaluru 560012, India.
ACS infectious diseases
|December 23, 2025
概括
研究人员稳定了sarbecovirus受体结合域 (RBDs),以创建一个候选疫苗. 这种稳定RBD尾酒表现出增强的稳定性,并引起了对小鼠多种sarbecoviruses的强有力的中和抗体.
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:
- 萨尔贝科病毒的动物性传播,如SARS-CoV-1和SARS-CoV-2,导致了严重的疫情.
- 病毒尖峰 (S) 蛋白,特别是它的受体结合域 (RBD),是中和抗体的关键目标.
- 开发针对萨尔贝科病毒的广泛保护性疫苗对于疫情准备至关重要.
研究的目的:
- 为了设计稳定受体结合域 (RBD) 来自各种萨尔贝科病毒的衍生物.
- 评估这些稳定RBD的稳定性,免疫性和中和能力.
- 评估稳定RBD尾酒作为未来沙贝科病毒流行病疫苗的潜力.
主要方法:
- 从SARS-CoV-1,WIV-1,RaTG13,RmYN02和BtKY72.72中构建和稳定RBD衍生物
- 通过与中和抗体结合测试来评估构造完整性.
- 评估热稳定性 (Tm) 和冷解后的稳定性.
- 用稳定RBD衍生物和尾酒免疫小鼠,然后对伪病毒进行中和试验.
主要成果:
- 稳定显著提高了RBD产量 (3-23倍) 和形状完整性.
- 稳定RBD表现出增强的热稳定性和冷化后延长的保质期.
- 用稳定RBDs的免疫接种,特别是在尾酒配方中,显著增加了中和标位 (约. 100倍) 在小鼠中.
- 疫苗配方在预先免疫的小鼠中没有显示免疫印记.
结论:
- 工程稳定沙贝科病毒RBD提供了更好的稳定性和产量.
- 稳定RBDs是强大的免疫原体,能够引起广泛的中和抗体反应.
- 一种稳定RBD合剂疫苗显示了对抗萨尔贝科病毒的广泛保护的潜力,这对于未来的流行病准备至关重要.
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