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Principal Investigator: Michael S Diamond
Organization: WASHINGTON UNIVERSITY
Fiscal Year: 2024
Award: $46,715,173
Funding agency: National Institute of Allergy and Infectious Diseases
SUMMARY.
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.
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