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持久的淋巴結(jié)擴(kuò)張與治療性疫苗接種的療效有關(guān)

更新時(shí)間:2024-08-02   點(diǎn)擊次數(shù):362次

中文摘要:

免疫接種后,淋巴結(jié)會(huì)動(dòng)態(tài)擴(kuò)張和收縮。已經(jīng)表征了使淋巴結(jié)早期擴(kuò)張的機(jī)械和細(xì)胞變化,但這種反應(yīng)的持久性及其對(duì)適應(yīng)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(jié)的高頻超聲成像,我們報(bào)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(biāo)準(zhǔn)疫苗制劑(如明礬)的動(dòng)物更有效和持久的淋巴結(jié)擴(kuò)張,并且持久和穩(wěn)健的淋巴結(jié)擴(kuò)張與疫苗效力和適應(yīng)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(jié)的機(jī)械和細(xì)胞外基質(zhì)特性,驅(qū)動(dòng)免疫細(xì)胞和基質(zhì)細(xì)胞的抗原依賴(lài)性增殖,并改變了樹(shù)突狀細(xì)胞和炎性單核細(xì)胞的轉(zhuǎn)錄特征。強(qiáng)有力地維持淋巴結(jié)擴(kuò)張的策略可能會(huì)提高疫苗接種結(jié)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)

在線時(shí)間:2024年5月6日


研究亮點(diǎn):

建模時(shí),我們?nèi)绻芯奘杉?xì)胞在模型里面的動(dòng)態(tài)曲線,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,對(duì)我們清除細(xì)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(xì)胞,除了用氯膦酸鹽脂質(zhì)體Clodronate Liposomes巨噬細(xì)胞清除劑清除單核巨噬細(xì)胞外,別的細(xì)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(jié)的體積變化和疫苗的關(guān)系。動(dòng)態(tài)曲線如下:

持久的淋巴結(jié)擴(kuò)張與治療性疫苗接種的療效有關(guān)


給藥方案:

有了淋巴結(jié)隨時(shí)間變化的動(dòng)態(tài)曲線,我們的給藥方案就有了依據(jù),本文里面。作者做了早期和晚期給藥設(shè)計(jì)。

持久的淋巴結(jié)擴(kuò)張與治療性疫苗接種的療效有關(guān)

持久的淋巴結(jié)擴(kuò)張與治療性疫苗接種的療效有關(guān)持久的淋巴結(jié)擴(kuò)張與治療性疫苗接種的療效有關(guān)


材料方法:

氯膦酸鹽脂質(zhì)體巨噬細(xì)胞清除劑Clodronateliposomes(liposoma,CP-005-005)清除巨噬細(xì)胞,研究淋巴結(jié),可以參考這篇文獻(xiàn)。

持久的淋巴結(jié)擴(kuò)張與治療性疫苗接種的療效有關(guān)


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