Cross-Species Immune System Reference

The objective of this project is to utilize mass cytometry to map immune responses in humans and animals that result from various stimuli (including biothreat agents and candidate medical countermeasures or MCMs). The human and animal responses will be compared and the resulting data will be made available to the community through an open-access resource. It is anticipated that this work may enhance the understanding of the diversity of immune responses elicited by these stimuli both within and across species. Specifically, the project provides a potential means to better understand the potential mechanism(s) of toxicity of biothreat agents, identify off target effects of candidate countermeasures, the mechanism(s) of action for candidate MCMs, and the comparability of these responses in animals and man. This data will be critical for not only facilitating interpretability of animal data but will provide novel and unprecedented potential to assess toxicity and off target effects. In addition the incorporation of studies with biothreat agents may provide new insight into pathogenesis and identify biomarkers as well as providing data that may assist in interpreting studies in animals to support countermeasures being advanced under the Animal Rule. Importantly, many MCMs will or are pursuing licensure through the Animal Rule. The Animal Rule requires "a reasonably well understood pathophysiological mechanism for the toxicity of the chemical, biological, radiological, or nuclear substance and its amelioration or prevention by the product as well as a demonstration of effectiveness in one or more species expected to react with a response predictive for humans". This project could provide an additional pathway to generating the necessary data to meet this regulatory standard.