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 rapidly generate countermeasures against current and future flavivirus and alphavirus threats. We will develop and optimize protein nanoparticle, virion-based, and mRNA vaccines, and mAb-based treatments to respond to emerging flaviviruses and alphaviruses with pandemic potential using a pathogen prototype and modular approach.
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
| Virus Family Focus | |
|---|---|
|
|
| Vaccine Approaches | Antibody Approaches |
|
|
FLARE Projects
Project 1: Vaccine Design Neurotropic Flaviviruses
PROJECT OVERVIEW:
Project 1 of the FLARE Center focuses on developing next-generation vaccines using West Nile virus (WNV) and tick-borne encephalitis virus (TBEV) as models for neurotropic flaviviruses. By targeting the structurally conserved E glycoprotein, the team employs innovative strategies like protein-based nanoparticles, stabilized dimers, and immune-focusing techniques to create modular vaccines adaptable to emerging flaviviruses. Collaborating with industry partners, the project rigorously tests candidates for immunogenicity and protection in animal models. These efforts aim to advance transformative vaccine platforms that strengthen global preparedness against neurotropic flavivirus threats
LEAD ORGANIZATION/INSTITUTION:
Ragon Institute
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- West Nile Virus, Tick-borne Encephalitis Virus
Project 2: Vaccine Design Epidemic Flaviviruses
PROJECT OVERVIEW:
FLARE Center Project 2 focuses on developing modular vaccine platforms for dengue virus type 2 (DENV2) and related flaviviruses, using a groundbreaking method to produce stable E protein homodimers that display potent, human-recognized neutralizing epitopes. Leveraging this "plug-and-play" approach, the project aims to create protein subunit and mRNA vaccines adaptable to current and future flavivirus outbreaks. Collaborating with industry partner Moderna and 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 combat diverse and emerging flavivirus threats
LEAD ORGANIZATION/INSTITUTION:
University of North Carolina at Chapel Hill
VIRUS FAMILY FOCUS:
PROTOTYPE VIRUSES:
- Dengue Virus
Project 3: Vaccine Design [mRNA] VEEV/CHIKV (alphaviruses)
PROJECT OVERVIEW:
FLARE Center Project 3 is advancing next-generation vaccines for Chikungunya virus (CHIKV) and Venezuelan Equine Encephalitis virus (VEEV), two alphaviruses that pose significant global health risks. 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 industry partner Moderna and the FLARE Center's cores, the project integrates innovative nanoparticle and mRNA technologies to create safe, effective vaccines. These efforts aim to deliver broad protection against alphaviruses, strengthening preparedness for future outbreaks
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 single-dose vaccines against alphavirus threats like chikungunya (CHIKV), Venezuelan equine encephalitis (VEEV), and eastern equine encephalitis viruses. This platform delivers rapid, durable protection, with promising results showing long-lasting immunity in non-human primates. The project will refine production protocols, optimize immunogenicity, and extend the platform to other alphaviruses to enable rapid response to future outbreaks. By creating a modular, thermostable, and highly effective vaccine platform, Project 4 strengthens preparedness for emerging alphavirus pandemics.
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 Flaviviruses and Alphaviruses
PROJECT OVERVIEW:
FLARE Center Project 5 is pioneering the discovery and optimization of human monoclonal antibodies (mAbs) to combat prototype flaviviruses like West Nile (WNV) and dengue (DENV), as well as alphaviruses like chikungunya (CHIKV). By using advanced antibody screening and computational approaches, the project develops 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 rapid-response "plug-and-play" workflow for emerging viral threats. These efforts aim to deliver effective, adaptable mAb therapies to strengthen global pandemic preparedness
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 targeting 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, mentoring underrepresented researchers, and strengthening communication with stakeholders, Core A drives the Center's mission to advance pandemic preparedness. Through its leadership and strategic support, Core A empowers innovative research and cultivates the next generation of scientists to combat emerging infectious diseases
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 emerging 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 for global pandemic preparedness
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 computational tools to support vaccine and therapeutic development 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 viral mutations to enhance immune response strategies. This work is pivotal in driving innovative solutions for global infectious disease 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 flaviviruses 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 for pandemic preparedness. This work ensures robust evaluation and readiness against future emerging viral threats.
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 flaviviruses 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 creation of effective countermeasures for current and future emerging viral threats.
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