Flavivirus and alphavirus revampp (flare)

The Flavivirus and Alphavirus REVAMPP (FLARE) Center, funded by a $46,715,173 Cooperative Agreement award from the National Institute of Allergy and Infectious Diseases (CFDA 93.855 Allergy and Infectious Diseases Research), is developing and optimizing protein nanoparticle, virion-based, and mRNA vaccine platforms, as well as monoclonal antibody-based treatments to rapidly respond to emerging flaviviruses and alphaviruses with pandemic potential. The Center integrates the work of multiple academic groups to design optimized immunogens that can be rapidly adapted to new viral threats within these virus families. Key goals include pairing specific antigen designs with vaccine platforms for a "plug and play" approach, and identifying correlates of protection to guide vaccine selection. The Center comprises five primary research projects focused on prototype flaviviruses and alphaviruses, supported by administrative, data management, and three scientific cores. Sub-awards support specialized contributions from institutions like Lawrence Livermore National Laboratory, University of North Carolina at Chapel Hill, and University of Pittsburgh.

Abstract

The flavivirus and alphavirus revampp (flare) center will develop and optimize protein nanoparticle, virion-based, and mrna vaccine platforms, and monoclonal antibody (MAB)-based treatments to rapidly respond to emerging flaviviruses and alphaviruses with pandemic potential. A key goal is to pair specific antigen designs and vaccine platforms so that successful paradigms can be rapidly adapted in a "plug and play" manner to emerging viruses within the same family. Our suite of antigen design strategies, vaccine platforms, state-of-the-art virological and immunological assays, extensive animal model experience, detailed analysis of correlates of protection, and experienced industry partners (e.g., moderna) will enable US to generate innovative vaccines and MAB combinations against key targeted prototype flaviviruses and alphaviruses, which then can be applied to related new threats. Moreover, with our collective academic experience in vaccinology and collaborative experience with industry partners, we can make informed go/no-go decisions to focus on antigens and vaccines with the greatest chance for clinical efficacy and safety. Our flare center integrates the work of multiple academic groups, with proven records of collaboration, that have the highest levels of expertise in flavivirus and alphavirus biology, antigen design, structural biology, antibody structure and function, MAB generation and characterization, vaccine development, b and t cell immunity, FC effector functions, and animal challenge studies, all working toward the goal of designing optimized immunogens for incorporation into lipid-encapsulated mrna, nanoparticles, or other vectors to create vaccines that can protect against infection and disease caused by existing and future flavivirus and alphavirus threats. Our flare center is composed of five primary research projects: two vaccine projects that collectively focus on prototype flaviviruses including west nile (WNV), tick-borne encephalitis (tbev), and dengue (denv) viruses; two vaccine projects, that focus on prototype alphaviruses including chikungunya (chikv) and venezuelan equine encephalitis (veev) viruses; and a MAB therapy project that focuses on both flaviviruses (WNV and denv) and alphaviruses (chikv). These projects are served by an administrative core, a data management core, and three scientific cores that perform structural biology and protein engineering, animal vaccination and challenge, and correlates of immune protection experiments in collaboration with multiple projects. Our network of expert investigators, innovative project and cores, and state-of-the art virological and immunological approaches will enable US to develop vaccine and MAB therapeutics against prototype flaviviruses and alphaviruses that can be readily and rapidly applied to other contemporary and newly emerging related viral threats.