中文摘要:
免疫接種后,淋巴結會動態擴張和收縮。已經表征了使淋巴結早期擴張的機械和細胞變化,但這種反應的持久性及其對適應性免疫和疫苗效力的影響尚不清楚。在這里,通過利用小鼠淋巴結的高頻超聲成像,我們報告了用含有模型抗原的介孔二氧化硅疫苗免疫的動物比給予推注免疫或標準疫苗制劑(如明礬)的動物更有效和持久的淋巴結擴張,并且持久和穩健的淋巴結擴張與疫苗效力和適應性免疫相關在黑色素瘤小鼠模型中接種疫苗后 100 天。免疫改變了淋巴結的機械和細胞外基質特性,驅動免疫細胞和基質細胞的抗原依賴性增殖,并改變了樹突狀細胞和炎性單核細胞的轉錄特征。強有力地維持淋巴結擴張的策略可能會提高疫苗接種結果。
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.
論文信息:
論文題目:Durable lymph-node expansion is associated with the efficacy of therapeutic vaccination
期刊名稱:Nature Biomedical Engineering
時間期卷:doi.org/10.1038/s41551-024-01209-3 pages685–700 (2024)
在線時間:2024年5月6日
研究亮點:
建模時,我們如果有巨噬細胞在模型里面的動態曲線,或者研究部位(研究靶點)的隨時間的動態變化曲線,對我們清除細胞的方案,尤其是給藥時間點,有很大的幫助。本文清除了多種細胞,除了用氯膦酸鹽脂質體Clodronate Liposomes巨噬細胞清除劑清除單核巨噬細胞外,別的細胞都是用的抗體。抗體清除成本高,需要注射多次,用量大。本文研究的時淋巴結的體積變化和疫苗的關系。動態曲線如下:
給藥方案:
有了淋巴結隨時間變化的動態曲線,我們的給藥方案就有了依據,本文里面。作者做了早期和晚期給藥設計。
材料方法:
氯膦酸鹽脂質體巨噬細胞清除劑Clodronateliposomes(liposoma,CP-005-005)清除巨噬細胞,研究淋巴結,可以參考這篇文獻。