REFINE: the eight Work Packages (WPs) of REFINE and their interrelationships
The continuous spread and the intensifying outbreaks of mosquito-borne orthoflaviviruses are becoming a growing global concern. These viruses, including West Nile, dengue, Zika, and yellow fever viruses, cause severe diseases and can trigger widespread epidemics, with dengue alone infecting over 400 million people annually. Factors such as climate change, globalization, and the proliferation of invasive mosquito species have contributed to the worldwide dissemination of these pathogens. In Europe, the range of Aedes mosquitoes, vectors for some of these viruses, is expanding by approximately 100 km per year. Recently, Europe has witnessed an upsurge in cases of West Nile virus (WNV) and Usutu virus (USUV) infection, both transmitted by the widely present Culex mosquitoes. In 2024, the largest geographical distribution of WNV in Europe in a single year was observed, with 1436 human cases of WNV infection, with 91% of cases hospitalized and 9% case fatality rate.
REFINE addresses this growing threat of mosquito-borne orthoflaviviruses. Its main goal is to acquire new fundamental knowledge to better design therapeutic targets as well as to create models to test the safety and effectiveness of new treatments, including antibodies, inhibitors and vaccines, for Phase I clinical trials. The six key objectives of REFINE are:
Characterize Genomic Diversity: Identify and characterize clinically relevant strains of orthoflaviviruses.
Develop Model Assays: Study virus-host interactions to understand the infection process.
Receptor and Pathway Characterization: Analyze receptors and pathways involved in the infection.
Identify and Test Intervention Strategies: Identify and test treatments like nanobodies, peptides, and monoclonal antibodies and assess their safety and effectiveness.
Characterize human Infections: Use patient samples to study key infection steps and receptors.
Establish a Validation Platform: Create a system for quick validation of new therapeutic interventions.
REFINE aims to improve Europe’s readiness and response to mosquito-borne viral diseases by developing and testing effective and safe vaccines and therapeutics. The REFINE team will uncover specific virus-host interactions and identify actionable targets that can block this process, thus providing solutions to this significant health security concern.
