PROVIDENT: Prepositioning Optimized Strategies for Vaccines and Immunotherapeutics against Diverse Emerging Infectious Threats

The overarching goal of PROVIDENT (Prepositioning Optimized Strategies for Vaccines and Immunotherapeu- tics against Diverse Emerging Infectious Threats) is to deliver "plug-and-play" vaccine and therapeutic an- tibody blueprints for emerging enveloped RNA viruses belonging to three families-Nairoviridae, Han- taviridae, and Paramyxoviridae. PROVIDENT is a highly interwoven partnership among 13 institutional teams from academia, government, and industry. Central to PROVIDENT is its focus on platform strategies that can rapidly advance manufacturable products with pathways to regulatory approval and plans for their commercialization through industry partners who are integral to our consortium. PROVIDENT will accomplish its goals by synthesizing the activities of four Research Projects, supported by three Research Cores and a Data Management Core, and overseen by the Administrative Core. Using a prototype virus strategy in Phase I, we will: (i) discover and dissect host factors and pathways critical for viral infection and pathogenesis and de- liver tools to other PROVIDENT components to facilitate vaccine and immunotherapeutic development; (ii) use advanced antigen engineering to refine vaccine design strategies through iterative assessments of immuno- genicity and protective efficacy to generate optimized vaccine immunogens; (iii) develop RNA vaccines and evaluate two platforms to optimize immunogenicity, protective efficacy, and safety and (iv) generate an adap- tive antibody development pipeline that will complement and inform vaccine design strategies. In Phase II, we will evaluate our prototype-optimized vaccine platforms against our divergent outgroup viruses in a series of timed exercises we term "sprints," which seek to generate a vaccine product ready to immunize animals in 10 days. In doing so, we will perform cross-family validations of our vaccine platforms for nairoviruses, han- taviruses, and paramyxoviruses as a rigorous challenge to the generalizability of the Phase I blueprint deliver- able, and either validate the blueprint or identify weaknesses for further refinement.