Table_2_A Comprehensive Atlas of Immunological Differences Between Humans, Mice, and Non-Human Primates.xlsx

Animal models are an integral part of the drug development and evaluation process. However, they are unsurprisingly imperfect reflections of humans, and the extent and nature of many immunological differences are unknown. With the rise of targeted and biological therapeutics, it is increasingly important that we understand the molecular differences in the immunological behavior of humans and model organisms. However, very few antibodies are raised against non-human primate antigens, and databases of cross-reactivity between species are incomplete. Thus, we screened 332 antibodies in five immune cell populations in blood from humans and four non-human primate species generating a comprehensive cross-reactivity catalog that includes cell type-specificity. We used this catalog to create large mass cytometry universal cross-species phenotyping and signaling panels for humans, along with three of the model organisms most similar to humans: rhesus and cynomolgus macaques and African green monkeys; and one of the mammalian models most widely used in drug development: C57BL/6 mice. As a proof-of-principle, we measured immune cell signaling responses across all five species to an array of 15 stimuli using mass cytometry. We found numerous instances of different cellular phenotypes and immune signaling events occurring within and between species, and detailed three examples (double-positive T cell frequency and signaling; granulocyte response to Bacillus anthracis antigen; and B cell subsets). We also explore the correlation of herpes simian B virus serostatus on the immune profile. Antibody panels and the full dataset generated are available online as a resource to enable future studies comparing immune responses across species during the evaluation of therapeutics.

动物模型是药物研发与评估过程中的核心组成部分。然而，它们不可避免地是对人类的不完美映射，众多免疫学差异的范围与性质尚不明确。随着针对性和生物疗法的兴起，深入了解人类与模型生物在免疫学行为上的分子差异变得愈发重要。然而，针对非人灵长类抗原的抗体极为稀少，且物种间交叉反应数据库尚不完善。因此，我们对来自人类及四种非人灵长类物种的血液中的五个免疫细胞群体进行了332种抗体的筛选，构建了一个包含细胞类型特异性的全面交叉反应目录。我们利用该目录创建了针对人类及其与人类最为相似的模型生物（包括猕猴、食蟹猴和非洲绿猴）以及药物研发中最常用的哺乳动物模型（C57BL/6小鼠）的大规模流式细胞术通用跨物种表型与信号分析板。作为原理验证，我们利用流式细胞术测量了所有五种物种对15种刺激的免疫细胞信号反应。我们发现，在物种间及其内部存在多种细胞表型和免疫信号事件，并详细阐述了三个实例（双阳性T细胞频率与信号、粒细胞对炭疽芽孢杆菌抗原的反应、B细胞亚群）。此外，我们还探讨了疱疹猴B病毒血清状态与免疫谱的相关性。抗体面板和生成的完整数据集已作为资源在线上提供，以促进未来在评估疗法时，对物种间免疫反应进行比较研究。