经过训练的ILC可以提供适应性免疫独立的抗流感保护
Wadzanai P Mboko1,2, Yuanyuan Wang3, Weiping Cao1
1Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Journal of virology
|August 4, 2025
概括
非复制性腺病毒可以训练先天性免疫系统,以保护其免受各种流感菌株的侵害,提供了一种超越传统疫苗的新策略. 这种方法可以增强先天的抗病毒免疫力,而不依赖于特定的适应性反应.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 传染性疾病 传染性疾病
背景情况:
- 季节性流感导致全球显著的死亡率,目前的疫苗显示出可变的疗效,并面临新兴耐药菌株的挑战.
- 现有的疫苗需要每年重新配方,并与新型或高度致病性流感亚型作斗争,突出了需要替代性保护策略的需要.
- 流行病学研究表明,某些疫苗,如Bacillus Calmette-Guérin (BCG),可以通过调节先天免疫系统,为各种病原体提供广泛的保护.
研究的目的:
- 调查由非复制性腺病毒诱导的受过训练的先天性免疫系统是否可以提供对广泛的流感病毒菌株的保护.
- 阐明腺病毒诱导的先天免疫训练和预防流感的细胞和分子机制.
- 评估腺病毒载体作为广泛抗病毒免疫的新战略的潜力.
主要方法:
- 用复制缺陷的人类腺病毒在小鼠模型中训练先天免疫系统.
- 随后,小鼠接受了多种流感病毒株 (H1N1,H3N2,H5N2,H7N9,H9N2) 的挑战.
- 分析了先天性淋巴细胞 (ILC) 及其激活标记物,干扰素刺激基因 (ISG),抗病毒途径和代谢概况. 在ILC缺乏的小鼠中进行了受过训练的ILC的收养转移.
主要成果:
- 复制缺陷的腺病毒在小鼠中对各种流感菌株产生了保护性免疫力,独立于流感特异性适应性免疫反应.
- 牛和黑猩猩的腺病毒也激活了人类的先天性淋巴细胞 (ILCs),并提供了对小鼠流感H3N2挑战的保护.
- 通过增加ILC1,ILC2和ILC3激活,增强ISG表达,高调抗病毒信号和ILCs代谢重编程来调节保护. 训练有素的ILC单独足以在ILC缺乏的小鼠中进行保护.
结论:
- 非复制性腺病毒可以有效地训练先天性免疫系统,提供针对多种流感病毒菌株的广泛保护.
- 这种策略通过激活ILCs和相关的分子途径来增强先天的抗病毒免疫力,提供了一种与传统疫苗相补充的新方法.
- 以腺病毒为媒介的先天性免疫训练有望为流行病的准备和通过建立强大,广泛的防御来打击新出现的传染病提供希望.
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