Sanofi Pasteur Ltd., Toronto, Ontario M2R 3T4, Canada; Department of Chemistry, York University, Toronto, Ontario M3J 1P3, Canada.
Fluidigm Corporation, Markham, Ontario L3R 4G5, Canada.
J Immunol Methods. 2021 Aug;495:113083. doi: 10.1016/j.jim.2021.113083. Epub 2021 Jun 3.
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.
评估疫苗免疫调节作用的能力对于新型疫苗的设计至关重要。虽然传统的动物模型已被广泛应用，但为了推进临床试验，更深入地了解新型疫苗在临床前开发阶段对人类的反应至关重要。需要一种转化方法，能够在不涉及人体暴露的情况下，捕捉人类模型中疫苗驱动反应的复杂性。在这里，我们设计了一个平台，使用新鲜的人类全血作为关键组件，研究疫苗配方对适应性免疫记忆反应。该反应通过使用高参数单细胞分析（Helios，CyTOF 系统）进行监测，能够快速、深入地描述抗原特异性增殖和预先存在的记忆 T 细胞的扩展，同时还能描述先天佐剂驱动的反应。在这项工作中，我们展示了该平台在细胞反应方面的能力，能够以前所未有的细节水平来描述记忆 T 细胞、B 细胞、单核细胞和 NK 细胞中生物相关的变化。我们将这种方法称为免疫图谱（Immunocartography），它有可能改变新型疫苗在临床前和临床开发过程中的评估方式。
