Washington University in St. Louis
FLARE | Flavivirus and Alphavirus ReVAMPP
The ReVAMMP Center (Flavivirus and Alphavirus ReVAMPP, FLARE) addresses the hypothesis that new approaches to antigen and vaccine design and monoclonal antibody (mAb) screening will promote the development of platform technologies that can generate safe and effective treatments against highly pathogenic flaviviruses and alphaviruses. Leveraging traditional methodologies alongside novel AI-assisted technologies, we are developing and optimizing protein nanoparticle and virion-based vaccines and mAb-based therapies to prevent and treat infections caused by orthoflaviviruses and alphaviruses circulating across the Americas using prototype pathogens and modular approaches. The ultimate goal of these studies is to develop prophylactic and therapeutic interventions for acute and chronic infections while mitigating the risk of chronic, long-term disease sequelae associated with these viral pathogens.
This Center is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number AI181960.
FLARE Overview
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FLARE Projects
Project 1: Vaccine Design Neurotropic Flaviviruses
PROJECT OVERVIEW:
Project 1 of the FLARE Center focuses on developing new vaccines for neurotropic orthoflaviviruses using West Nile virus (WNV) and tick-borne encephalitis virus (TBEV) as model pathogens. By targeting the structurally conserved E glycoprotein, the team employs innovative strategies such as protein-based nanoparticles and stabilized E dimers as well as immune-focusing techniques to create modular vaccines adaptable for current and emerging flaviviruses. The project rigorously tests candidates for immunogenicity and protection in animal models. These efforts aim to advance transformative vaccine platforms that strengthen our ability to treat highly pathogenic neurotropic orthoflavivirus infections.
LEAD ORGANIZATION/INSTITUTION:
Ragon Institute
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- West Nile Virus, Tick-borne Encephalitis Virus
Project 2: Vaccine Design Epidemic Orthoflaviviruses
PROJECT OVERVIEW:
FLARE Center Project 2 focuses on developing modular vaccine platforms for dengue virus type 2 (DENV2) and related highly pathogenic orthoflaviviruses, using a groundbreaking method to produce stable E protein homodimers that display potent neutralizing epitopes. Leveraging this "plug-and-play" approach, the project aims to create protein subunit vaccines adaptable to current and emerging flaviviruses. Collaborating with other FLARE projects and cores, Project 2 refines immunogenic designs, evaluates cross-protective immunity, and advances vaccine candidates through preclinical testing. This work lays the foundation for transformative vaccines to treat orthoflavivirus infections.
LEAD ORGANIZATION/INSTITUTION:
University of North Carolina at Chapel Hill
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Dengue Virus
Project 3: Vaccine Design [nanoparticle] VEEV/CHIKV (alphaviruses)
PROJECT OVERVIEW:
FLARE Center Project 3 is advancing next-generation vaccines for Chikungunya virus (CHIKV) and Venezuelan Equine Encephalitis virus (VEEV), alphaviruses that pose significant health risks in the Americas. By leveraging structural conservation among alphaviruses and targeting key epitopes on the E1/E2 glycoprotein complex, the project employs a "plug-and-play" approach to develop adaptable immunogen and vaccine platforms. Collaborating with the FLARE Center's cores, the project integrates innovative nanoparticle technologies to create safe, effective vaccines. These efforts aim to deliver broad protection against alphaviruses.
LEAD ORGANIZATION/INSTITUTION:
Albert Einstein College of Medicine
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Chikungunya Virus, Venezuelan Equine Encephalitis Virus
Project 4: Vaccine Design [insect alphavirus chimera] VEEV/CHIKV (alphaviruses)
PROJECT OVERVIEW:
FLARE Center Project 4 is developing an innovative vaccine platform using Eilat virus (EILV), a safe, insect-specific alphavirus, as a backbone for creating vaccines against highly pathogenic alphaviruses like chikungunya (CHIKV), Venezuelan equine encephalitis (VEEV), and eastern equine encephalitis (EEEV) viruses. This platform delivers rapid, durable protection, with promising results showing long-lasting immunity in non-human primates. The project will create a modular, thermostable, and highly effective vaccine platform, optimize production protocols and immunogenicity, and extend the platform to enable treatment of current and emerging alphavirus infections.
LEAD ORGANIZATION/INSTITUTION:
University of Texas Medical Branch at Galveston
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Chikungunya Virus, Venezuelan Equine Encephalitis Virus, Western Equine Encephalitis Virus
Project 5: Monoclonal Antibody Development Orthoflaviviruses and Alphaviruses
PROJECT OVERVIEW:
FLARE Center Project 5 is pioneering the discovery and optimization of human monoclonal antibodies (mAbs) to combat highly pathogenic orthoflaviviruses like West Nile (WNV) and dengue (DENV), as well as alphaviruses like chikungunya (CHIKV). By using advanced antibody screening and AI-assisted computational approaches, the project will develop potent, synergistic mAb combinations that prevent resistance and extend therapeutic efficacy. Collaborating with Core C and other projects, this work informs vaccine design while refining a "plug-and-play" workflow to deliver effective, adaptable mAb therapies for current and emerging orthoflavivirus and alphavirus infections.
LEAD ORGANIZATION/INSTITUTION:
Vanderbilt University Medical Center
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- West Nile Virus, Dengue Virus, Chikungunya Virus, Mayaro Virus
FLARE Cores
Each ReVAMPP Center has an Administrative Core and a Data Management Core. Centers can also have up to three Scientific Cores to support resources and/or facilities that are essential for the collaborative research activities in two or more research projects.
CORE SERVICES:
Administrative
LEAD ORGANIZATION:
Washington University in St. Louis
The Administrative Core A is the central hub of the FLARE Center, ensuring seamless coordination, compliance, and support for research activities treating flaviviruses and alphaviruses. Core A provides critical administrative, financial, and operational oversight while fostering collaboration within the FLARE Center and the broader ReVAMPP network. By facilitating data sharing and strengthening communication with stakeholders, Core A drives the Center's mission to develop new ways to treat highly pathogenic flavivirus and alphavirus infections. Through its leadership and strategic support, Core A empowers innovative research and cultivates the next generation of scientists to benefit human health of the American public.
CORE SERVICES:
Data Stewardship
LEAD ORGANIZATION:
Washington University in St. Louis
The Data Management Core B is the central hub for managing, analyzing, and harmonizing data within the FLARE Center, supporting research on vaccines and therapies for highly pathogenic flaviviruses and alphaviruses. By developing advanced cloud-based platforms and implementing rigorous quality-control systems, Core B ensures the generation and dissemination of high-quality, FAIR-compliant (Findable, Accessible, Interoperable, Reusable) data. Collaborating across the ReVAMPP Network and with external stakeholders, Core B facilitates seamless data sharing and visualization to accelerate scientific discovery. This integrative approach empowers the FLARE Center to drive innovative solutions to treat orthoflavivirus and alphavirus infections.
CORE SERVICES:
Structure Analysis
Computational Analysis
Protein Engineering
LEAD ORGANIZATION:
Purdue University
The Structure, Computational, and Protein Engineering Core C leverages advanced structural biology, biophysics, and AI-assisted computational tools to support vaccine and therapeutic development for highly pathogenic orthoflavivirus and alphaviruses across the center. Using techniques like X-ray crystallography and cryo-electron microscopy, Core C analyzes antigen-antibody interactions at the molecular level to guide the design and refinement of immunogens and antibody therapies. By collaborating closely with all projects and cores, Core C ensures data-driven advancements, including engineering reagents and studying viruses to enhance immune response strategies. This work is pivotal in driving innovative solutions for current and emerging health challenges.
CORE SERVICES:
Animal Models
LEAD ORGANIZATION:
Oregon Health and Science University
The Animal Vaccination, Immunogenicity, and Challenge Model Core D plays a critical role in advancing vaccines and monoclonal antibodies against highly pathogenic orthoflaviviruses and alphaviruses, including Dengue, West Nile, and Chikungunya viruses. By leveraging proven animal models and the expertise of leading scientists, Core D rigorously tests and refines vaccine candidates and therapeutic approaches. With standardized protocols and close collaboration across the FLARE Center, Core D generates high-quality, comparable data to identify optimal platforms and designs to better treat flavivirus and alphavirus infection.
CORE SERVICES:
Correlates of Protection
LEAD ORGANIZATION:
Washington University in St. Louis
The Correlates of Protection Core E utilizes advanced immune assays to evaluate the efficacy and safety of vaccines and monoclonal antibodies against highly pathogenic orthoflaviviruses and alphaviruses, such as Dengue, West Nile, and Chikungunya viruses. Led by renowned experts, Core E establishes high-throughput testing methods and leverages clinical data to validate and refine assays. By identifying immune correlates of protection, Core E provides critical insights to guide vaccine development and therapeutic strategies. This work accelerates the development of effective treatments for orthoflavivirus and alphavirus infections, which are critical for protecting the health of the American Public.
FLARE Participating Organizations & Institutions
- Albert Einstein College of Medicine
- Oregon Health and Science University
- Purdue University
- Ragon Institute
- The University of Texas Medical Branch
- University of North Carolina at Chapel Hill
- Vanderbilt University Medical Center
- Washington University School of Medicine