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Immunocartography: Charting vaccine-driven immunity by applying single cell proteomics to an in vitro human model
Journal of Immunological Methods ( IF 2.2 ) Pub Date : 2021-06-03 , DOI: 10.1016/j.jim.2021.113083
Jessica S Duprez 1 , Michael Cohen 2 , Stephen Li 2 , Derek Wilson 3 , Roger H Brookes 4 , D Andrew James 1
Affiliation  

The ability to measure immunomodulatory effects of a vaccine is crucial for novel vaccine design. While traditional animal models have been effective, a better understanding of the response in humans to new vaccines in pre-clinical development is critical for advancement to clinical trials. A translational methodology that can capture the complexity of a vaccine-driven response in a human model, which does not require human exposure, is needed. Here we have designed a platform that uses fresh human whole blood as a key component to study the adaptive immune memory response to vaccine formulations. The response is monitored by high-parameter single cell analysis using mass cytometry (Helios, CyTOF System), allowing for a rapid, in-depth characterization of antigen specific proliferation and expansion of preexisting memory T cells in concert with an innate adjuvant-driven response. In this work we demonstrate the capability of this platform to characterize biologically relevant changes in the cellular response across memory T-cells, B cells, monocytes, and NK cells, at an unprecedented level of detail. This approach that we call Immunocartography has the potential to transform the way new vaccines can be assessed before and throughout clinical development.



中文翻译:

免疫制图:通过将单细胞蛋白质组学应用于体外人体模型来绘制疫苗驱动的免疫图

测量疫苗免疫调节作用的能力对于新型疫苗设计至关重要。虽然传统的动物模型是有效的,但在临床前开发中更好地了解人类对新疫苗的反应对于推进临床试验至关重要。需要一种可以在人体模型中捕捉疫苗驱动反应的复杂性的转化方法,该方法不需要人体接触。在这里,我们设计了一个平台,该平台使用新鲜的人类全血作为关键成分来研究对疫苗制剂的适应性免疫记忆反应。使用质谱流式细胞术(Helios,CyTOF 系统)通过高参数单细胞分析监测反应,从而实现快速、深入表征抗原特异性增殖和预先存在的记忆 T 细胞的扩增与先天佐剂驱动的反应相一致。在这项工作中,我们展示了该平台以前所未有的细节水平表征记忆 T 细胞、B 细胞、单核细胞和 NK 细胞的细胞反应的生物学相关变化的能力。这种我们称之为免疫制图的方法有可能改变在临床开发之前和整个临床开发过程中评估新疫苗的方式。

更新日期:2021-06-07
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