中文摘要:
免疫接種后,淋巴結會(huì )動(dòng)態(tài)擴張和收縮。已經(jīng)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(guò)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(dòng)物比給予推注免疫或標準疫苗制劑(如明礬)的動(dòng)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(guān)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(zhì)特性,驅動(dòng)免疫細胞和基質(zhì)細胞的抗原依賴(lài)性增殖,并改變了樹(shù)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(huì )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(chēng):Nature Biomedical Engineering
時(shí)間期卷:doi.org/10.1038/s41551-024-01209-3 pages685–700 (2024)
在線(xiàn)時(shí)間:2024年5月6日
研究亮點(diǎn):
建模時(shí),我們如果有巨噬細胞在模型里面的動(dòng)態(tài)曲線(xiàn),或者研究部位(研究靶點(diǎn))的隨時(shí)間的動(dòng)態(tài)變化曲線(xiàn),對我們清除細胞的方案,尤其是給藥時(shí)間點(diǎn),有很大的幫助。本文清除了多種細胞,除了用氯膦酸鹽脂質(zhì)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??贵w清除成本高,需要注射多次,用量大。本文研究的時(shí)淋巴結的體積變化和疫苗的關(guān)系。動(dòng)態(tài)曲線(xiàn)如下:
給藥方案:
有了淋巴結隨時(shí)間變化的動(dòng)態(tài)曲線(xiàn),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(zhì)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。
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