RAPID Ebola outbreak: A Web Tool for Tracking Pathogen Evolution Impact on Immune Responses

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The current Ebola outbreak, similar to the swine-origin influenza outbreak of 2009, is characterized by emergence of new strains of viruses that have previously circulated in animal reservoirs and gained the ability for human-to-human transmission. As the virus adapts to this new mode of transmission, multiple mutations occur. Thus, data from previous studies of the parent virus might no longer be relevant. This recurring situation of viruses mutating as they adapt makes it necessary to develop tools to rapidly re-analyze existing data for their relevance as new sequences of circulating strains become available. The focus of this project is to provide such a tool for monitoring the effect of mutations in protein sites of immune recognition, also known as epitopes, in a given pathogen. Applied to Ebola virus, the proposed tool will have an immediate impact on addressing in real time, as the virus evolves, the need for monitoring and developing new products for treating, preventing, and diagnosing Ebola. This project has three goals: (1) To develop a web tool that will take as input new pathogen sequences and, in the case of Ebola, automatically gather them from GenBank. These sequences will be cross-compared for epitope data in the IEDB (Immune Epitope Database), and conservancy analysis will be run on known and predicted epitopes. (2) To connect the tool to the University of California Santa Cruz (UCSC) Genome Browser to allow visualizing protein and epitope data. (3) To incorporate into and make the tool available on the IEDB website to ensure sustainability and broader access.The project is focused on basic research on how pathogen evolution impacts recognition by the host immune system. The tool, which will simultaneously capture, monitor, analyze, and visualize in real time data on pathogen evolution and immune epitopes, should allow the researchers to address questions such as which pathogen proteins and signature sites in proteins enable pathogen evolution and adaptation; do new mutations change antigenic properties of pathogen proteins; and how do mutation affect the molecular recognition of pathogen antigens by the immune receptors. The tool will enable rapid monitoring of any emerging virus strain and provide insight on how mutations affect conservancy of known epitopes and antigenicity of the virus. The B and T cell epitopes for each viral protein will be predicted using the IEDB Analysis Resource and be provided to the community for further investigation of potential peptide-based products (therapeutics, vaccines, diagnostics). Integration with the UCSC Genome Browser and IEDB will provide high visibility and broader access to the tool. The proposed tool will be applicable to a wide range of pathogens, ensuring the community preparedness for a rapid response to future outbreaks. The project will also broaden participation of under-represented groups in science, will be integrated into courses the PI teaches and will be integrated into the PI?s outreach activities, including mentoring high-school students. A workshop and lectures on the project?s topic will be given to K-12 teachers and students through the SDSC educational programs TeacherTECH and StudentTECH.