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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 immunological behavior of humans and model organisms. Thus, we profiled a large number of healthy humans, along with three of the model organisms most similar to humans: rhesus and cynomolgus macaques and African green monkeys; and the most widely used mammalian model: mice. Using cross-species, universal phenotyping and signaling panels, we measured immune cell signaling responses to an array of 15 stimuli using CyTOF mass cytometry. We found numerous instances of different cellular phenotypes and immune signaling events occurring within and between species with likely effects on evaluation of therapeutics, and detail 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. The full dataset is available online at https://flowrepository.org (accession FR-FCM-Z2ZY) and https://immuneatlas.org.
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