基于域的mRNA疫苗编码尖端蛋白N-终端和受体结合域,可以提供对SARS-CoV-2的保护
Guillaume B E Stewart-Jones1, Sayda M Elbashir1, Kai Wu1
1Moderna, Inc., Cambridge, MA 02139, USA.
Science translational medicine
|September 13, 2023
概括
与现有疫苗相比,一种新的信使RNA (mRNA) 疫苗,mRNA-1283,针对SARS-CoV-2尖端蛋白的特定域,显示出增强的稳定性和强大的免疫反应,对抗各种病毒变异.
科学领域:
- 疫苗学 疫苗学 疫苗学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 使者RNA (mRNA) 疫苗已被证明对2019年冠状病毒疾病 (COVID-19) 有效.
- 需要进一步的进展来提高疫苗的效力,免疫范围和热稳定性.
- 针对SARS-CoV-2尖端蛋白的特定域提供了改进疫苗设计的潜在策略.
研究的目的:
- 设计和评估基于新型域的mRNA疫苗,编码SARS-CoV-2尖端蛋白的受体结合域 (RBD) 或N终端域 (NTD).
- 为了比较一种新型NTD-RBD相关的mRNA疫苗 (mRNA-1283) 与临床上可用的全长尖端蛋白mRNA疫苗 (mRNA-1273) 的免疫性,抗原表达和稳定性.
- 在临床前模型中评估mRNA-1283对各种SARS-CoV-2变体的保护效果.
主要方法:
- 基于域的mRNA疫苗的设计和合成,编码野生类型尖蛋白RBD或NTD,单独或组合.
- 评估候选疫苗在冷藏温度 (2°至8°C) 的抗原表达,抗体反应和稳定性.
- 在使用mRNA-1283和mRNA-1273的BALB/c和K18-hACE2小鼠进行临床前挑战性研究,评估免疫反应和对野生型,Beta,Delta和Omicron (BA.1) SARS-CoV-2变体的保护.
主要成果:
- 与NTD-RBD连接的mRNA-1283候选人表现出优越的抗原表达,抗体反应,以及在2°至8°C的稳定性,与mRNA-1273.3相比.
- 与mRNA-1273相比,mRNA-1283在多种变体 (野生型,Beta,Delta,Omicron BA.1) 中引起了类似或更强的免疫反应,特别是在较低的疫苗剂量时.
- 在K18-hACE2小鼠中,mRNA-1283和mRNA-1273都提供了与SARS-CoV-2Delta和Omicron变体挑战的可比保护.
结论:
- mRNA-1283表现出改进的特征,包括增强的稳定性和强大的免疫性对抗一系列SARS-CoV-2变种.
- 这些临床前发现支持mRNA-1283.3的临床发展.
- mRNA-1283已经进入临床试验 (NCT05137236),表明作为下一代COVID-19疫苗的有前途潜力.
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