DEVELOPMENT OF FERRET REAGENTS FOR USE IN THE CHARACTERIZATION OF IMMUNE RESPONSES TO RESPIRATORY INFECTIONS IN THE FERRET MODEL.

This proposal addresses a pressing need to develop reagents to better understand and describe the immune response to infection and support biomarker and countermeasure development through immunologic analyses of respiratory infections in the ferret. Select ferret-specific immunoreagents will be generated and tested in the context of influenza infection, where the ferret is considered to be the gold standard of preclinical research. The specific and measurable technical objectives are to generate and test monoclonal antibodies against 10 ferret-specific cytokines and chemokines and 4 ferret-specific cell surface markers expressed on innate immune cells. The focus on soluble mediators and cell surface markers of nonlymphocytic cell types, such as macrophages and dendritic cells, will add value by complementing existing immunoreagents and the ongoing generation of B and T cell surface markers and immunoglobulin components. Being enabled to characterize the immune response in ferrets would represent a key innovation in the ability to deploy a preclinical model of respiratory infections. The ferret-specific immunoreagents produced via this work will be made commercially available at the end of Phase 1, and Luminex kits for quantitative multiplex analyses of innate immune mediators will be developed in Phase 2.