Antibody and Reagent Development Core

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Core B - Project Summary/Abstract Filoviruses, which are NIAID category A priority pathogens, can subvert host immune systems to facilitate viral replication, resulting in human case fatality rates as high as 90%. The filoviral genome encodes for seven to nine proteins. Despite the small number of genes, limited information is available on the specific mechanisms by which different viral-viral and viral-host interactions contribute to filoviral replication and pathogenesis, hindering the development of antivirals or vaccines. The Antibody and Reagent Development Core (Core B) will provide critical reagents and support for the overall scientific mission and facilitate the characterization of these interactions. Specifically, Core B will provide a unique set of standardized antibodies, cell-lines, and mouse models that will be disseminated amongst the Research Projects (RPs) and Cores of the PPG. In consultation with the Administrative Core (Core A) and the PPG leadership, Core B will prioritize experiments to ensure that reagents will be readily available to the RPs and Cores for use, validation, and characterization of interfaces between viral proteins and host factors that impact steps in the filoviral replication cycle. Core B will develop mouse monoclonal and synthetic antibodies against Ebola and Marburg viral proteins, generate knockout cell lines of host factors, and generate conditional knockout mouse models of select host factors identified by RP01, RP02, RP03, and Core C when such reagents are not commercially available. Given the need for a unified reagent development pipeline, the scientific core activity for Core B is justified.