由高度保存的人类B,CD4诱导的交叉保护
Swayam Prakash1, Nisha R Dhanushkodi1, Latifa Zayou1
1Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.
bioRxiv : the preprint server for biology
|June 9, 2023
概括
一种新型的多副本泛冠状病毒疫苗提供了针对SARS-CoV-2关注变种 (VOCs) 的广泛保护. 这种疫苗是安全的,并引起强大的免疫反应,减少COVID-19的严重程度和死亡率.
科学领域:
- 免疫学 免疫学 免疫学
- 疫苗学 疫苗学 疫苗学
- 病毒学 病毒学
背景情况:
- 由SARS-CoV-2引起的COVID-19大流行,由于出现了许多令人担忧的变种 (VOCs),继续构成重大全球健康威胁.
- 现有的疫苗在提供针对不断演变的SARS-CoV-2菌株的广泛保护方面面临挑战,需要开发下一代疫苗.
- 与COVID-19相关的高死亡率强调迫切需要有效的泛冠状病毒疫苗.
研究的目的:
- 设计和评估一种基于多个表位的全冠状病毒新型疫苗.
- 评估疫苗对多种SARS-CoV-2VOC的安全性,免疫性和交叉保护疗效.
- 研究疫苗在人性化的小鼠模型中引起保守T细胞反应的能力.
主要方法:
- 开发一种多表位疫苗,其中包含来自SARS-CoV-2的保存的B,CD4+和CD8+T细胞表位.
- 使用三重转基因h-ACE-2-HLA-A2/DR小鼠模型进行临床前评估.
- 评估疫苗的安全性,免疫性 (包括肺部T细胞反应) 和对六种SARS-CoV-2VOCs的保护.
主要成果:
- 在实验模型中发现泛冠疫苗是安全的.
- 该疫苗成功诱导了高频率的功能性CD8+和CD4+T细胞 (TEM和TRM).
- 观察到对病毒复制,肺病理和与六种主要SARS-CoV-2 VOC (阿尔法,贝塔,玛,三角形,欧米克朗) 相关的死亡率有强大的保护.
结论:
- 针对保存的SARS-CoV-2表位的多表位疫苗策略在诱导交叉保护性免疫力方面是有效的.
- 这种泛冠状病毒疫苗清除了病毒复制,并减少了COVID-19相关的肺病理和死亡.
- 这些发现支持该疫苗的开发,作为对抗SARS-CoV-2VOCs的下一代解决方案.
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