单组件多层自我组装蛋白质纳米粒子显示矩阵蛋白2的细胞外域作为泛流感A疫苗
Keegan Braz Gomes1, Yi-Nan Zhang1, Yi-Zong Lee1
1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, United States.
ACS nano
|November 21, 2023
概括
一种具有M2e抗原的新型自组装蛋白纳米粒子 (SApNP) 疫苗提供了对流感A病毒的广泛保护. 一次剂量与强大的辅助剂在小鼠中提供了90%的保护,显示出普遍流感疫苗的前景.
科学领域:
- 免疫学 免疫学 免疫学
- 疫苗学 疫苗学 疫苗学
- 纳米技术 纳米技术
背景情况:
- 开发一种交叉保护型泛型流感A疫苗是一个关键的挑战.
- 矩阵蛋白2 (M2e) 的保存的细胞外域是通用流感疫苗的目标.
研究的目的:
- 设计和评估M2e作为流感A疫苗候选人的单组件自我组装蛋白质纳米粒子 (SApNPs).
- 评估M2e呈现SApNP对致命流感A病毒的疗效的挑战.
主要方法:
- SApNP被设计为显示来自人类,禽类和猪宿主 (M2ex3) 的M2e的并列重复.
- 疫苗的有效性在与H1N1和H3N2流感A病毒挑战的小鼠中进行了测试.
- 通过评估抗体和T细胞反应以及淋巴结中的疫苗稳定性来评估免疫性.
主要成果:
- 与可溶性M2e抗原相比,M2ex3SApNP显著提高了生存率并减少了体重减轻.
- 与辅助剂配制的SApNP显示在淋巴结中持续存在,并诱导长期存在的免疫反应.
- 一次低剂量的M2ex3SApNP与TLR9或STING激动剂辅助剂一起,对致命的H1N1挑战提供了90%的保护.
结论:
- 呈现M2ex3的SApNP是针对各种流感A菌株的有效疫苗候选者.
- 在SApNP平台,结合强大的辅助剂,诱导强大而持久的保护性免疫力.
- 这一战略有望为开发通用泛型流感A疫苗提供希望.
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