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Durable lymph-node expansion is associated with the efficacy of therapeutic vaccination
Nature Biomedical Engineering ( IF 28.1 ) Pub Date : 2024-05-06 , DOI: 10.1038/s41551-024-01209-3
Alexander J. Najibi , Ryan S. Lane , Miguel C. Sobral , Giovanni Bovone , Shawn Kang , Benjamin R. Freedman , Joel Gutierrez Estupinan , Alberto Elosegui-Artola , Christina M. Tringides , Maxence O. Dellacherie , Katherine Williams , Hamza Ijaz , Sören Müller , Shannon J. Turley , David J. Mooney

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.



中文翻译:

持久的淋巴结扩张与治疗性疫苗接种的功效相关

免疫后,淋巴结动态扩张和收缩。使淋巴结早期扩张的机械和细胞变化已经被表征,但这种反应的持久性及其对适应性免疫和疫苗功效的影响尚不清楚。在这里,通过利用小鼠淋巴结的高频超声成像,我们报告说,与接受推注免疫或标准疫苗制剂(例如,明矾,并且在黑色素瘤小鼠模型中,持久而强劲的淋巴结扩张与疫苗功效和接种后 100 天的适应性免疫有关。免疫改变了淋巴结的机械和细胞外基质特性,驱动了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效果。

更新日期:2024-05-07
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