持久的淋巴結(jié)擴(kuò)張與治療性疫苗接種的療效有關(guān)

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。抗體清除成本高，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：

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)。

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)。