中文摘要:
免疫接种后,淋巴结会动态扩张和收缩。已经表征了使淋巴结早期扩张的机械和细胞变化,但这种反应的持久性及其对适应性免疫和疫苗效力的影响尚不清楚。在这里,通过利用小鼠淋巴结的高频超声成像,我们报告了用含有模型抗原的介孔二氧化硅疫苗免疫的动物比给予推注免疫或标准疫苗制剂(如明矾)的动物更有效和持久的淋巴结扩张,并且持久和稳健的淋巴结扩张与疫苗效力和适应性免疫相关在黑色素瘤小鼠模型中接种疫苗后 100 天。免疫改变了淋巴结的机械和细胞外基质特性,驱动免疫细胞和基质细胞的抗原依赖性增殖,并改变了树突状细胞和炎性单核细胞的转录特征。强有力地维持淋巴结扩张的策略可能会提高疫苗接种结果。
英文摘要:
Following immunization, lymph nodes dynamically expand and contract. The mechanical and cellular changes enabling the early-stage expansion of lymph nodes have been characterized, yet the durability of such responses and their implications for adaptive immunity and vaccine efficacy are unknown. Here, by leveraging high-frequency ultrasound imaging of the lymph nodes of mice, we report more potent and persistent lymph-node expansion for animals immunized with a mesoporous silica vaccine incorporating a model antigen than for animals given bolus immunization or standard vaccine formulations such as alum, and that durable and robust lymph-node expansion was associated with vaccine efficacy and adaptive immunity for 100 days post-vaccination in a mouse model of melanoma. Immunization altered the mechanical and extracellular-matrix properties of the lymph nodes, drove antigen-dependent proliferation of immune and stromal cells, and altered the transcriptional features of dendritic cells and inflammatory monocytes. Strategies that robustly maintain lymph-node expansion may result in enhanced vaccination outcomes.
论文信息:
论文题目:Durable lymph-node expansion is associated with the efficacy of therapeutic vaccination
期刊名称:Nature Biomedical Engineering
时间期卷:doi.org/10.1038/s41551-024-01209-3 685–700 (2024)
在线时间:2024年5月6日
研究亮点:
建模时,我们如果有巨噬细胞在模型里面的动态曲线,或者研究部位(研究靶点)的随时间的动态变化曲线,对我们清除细胞的方案,尤其是给药时间点,有很大的帮助。本文清除了多种细胞,除了用氯膦酸盐脂质体Clodronate Liposomes巨噬细胞清除剂清除单核巨噬细胞外,别的细胞都是用的抗体。抗体清除成本高,需要注射多次,用量大。本文研究的时淋巴结的体积变化和疫苗的关系。动态曲线如下:
给药方案:
有了淋巴结随时间变化的动态曲线,我们的给药方案就有了依据,本文里面。作者做了早期和晚期给药设计。
材料方法:
氯膦酸盐脂质体巨噬细胞清除剂Clodronateliposomes(liposoma,CP-005-005)清除巨噬细胞,研究淋巴结,可以参考这篇文献。