经过计算设计的Spike抗原诱导对SARS-COV-2变种的广度进行中和反应
Sneha Vishwanath1, George William Carnell1, Martina Billmeier2
1Lab of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, United Kingdom.
NPJ vaccines
|September 9, 2024
概括
新型尖峰抗原是通过计算设计的,旨在对抗不断演变的SARS-CoV-2关注变体 (VOCs). 这些抗原在动物模型中表现出广泛的中和抗体反应,为下一代疫苗提供了一个有希望的战略.
科学领域:
- 免疫学 免疫学 免疫学
- 疫苗学 疫苗学 疫苗学
- 计算生物学 计算生物学
背景情况:
- 随着SARS-CoV-2的不断演变,需要更新的疫苗来应对令人担忧的变种 (VOC).
- 现有的疫苗可能面临对新出现的SARS-CoV-2菌株的有效性降低.
- 广泛中和抗原的开发对于长期的流行病控制至关重要.
研究的目的:
- 通过计算设计基于尖峰的新型抗原,对SARS-CoV-2 VOC进行广泛的中和.
- 在临床前模型中评估设计抗原的免疫性和中和能力.
- 评估用于下一代疫苗的结构知情抗原设计的潜力.
主要方法:
- 在三种基于的抗原 (T2_32,T2_35,T2_36) 的in-silico设计中,使用了前-Delta和后-Gamma SARS-CoV-2 序列数据.
- 用T2_32抗原对几内亚猪进行DNA原始增强免疫.
- 不同类型的增强用修改的疫苗安卡拉表达T2_32.
- 在使用T2_32,T2_35和T2_36抗原的小鼠中进行mRNA免疫接种,与Omicron BA.1尖峰抗原相比.
主要成果:
- T2_32抗原在DNA主要增强模型中,与武汉-1峰值相比,对VOCs表现出优异的中和反应.
- 使用MVA-T2_32的异质增强在所有原始动物中扩大了中和免疫反应.
- 在mRNA免疫模型中,T2_32,T2_35和T2_36抗原显示出比Omicron BA.1尖峰抗原更广泛的中和能力.
结论:
- 计算衍生,结构知情的尖峰抗原可以诱导广泛的中和免疫反应,对各种SARS-CoV-2VOCs.
- 设计的抗原显示出开发下一代疫苗的潜力,这些疫苗有效地对抗不断演变的病毒菌株.
- 这种方法突出了在基抗原设计的实用性,用于解决像SARS-CoV-2这样快速突变的病毒.
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