Flaviviruses—including Zika, dengue, West Nile, and yellow fever—are mosquito-borne pathogens of increasing global concern. Their spread is rising due to climate change and urbanization, leading to the emergence of new outbreaks in regions such as Europe, where record numbers of local cases have been reported. In August 2025, the European Centre for Disease Prevention and Control warned that West Nile virus could become “the new normal” for Europe. Many flaviviruses lack effective vaccines, and even for yellow fever vaccine, the immune mechanisms underlying its exceptional protection remain incompletely understood.
Yellow4FLAVI’s mission is to unlock the immune “blueprint” of the yellow fever vaccine (YF17D)—one of humanity’s most successful vaccines—in order to correlate the virus structure with its immunogenicity and guide the design of safer, next-generation flavivirus vaccines. The project aims to tailor vaccines to a diverse population with co-circulation of Flaviviruses and maximize public trust through robust, science-based risk communication.
Yellow4FLAVI leverages advanced technologies: cryo-electron microscopy, super-resolution microscopy, spatial transcriptomics, high-dimensional spectral flow cytometry, single-cell RNA sequencing, advanced cell engineering, and animal/clinical and social studies, both in Europe and in dengue-endemic Colombia. This comprehensive approach tracks events from the very first molecular and cellular responses at the vaccine injection site to community perceptions of vaccination.
Social acceptance is crucial for vaccine success. The project incorporates comparative quantitative and qualitative social studies on vaccine hesitancy in Germany and Colombia, which will enable developing context-adapted, evidence-based communication methods.
Main objectives:
1. To understand how the structure of the virus affects how the immune system recognizes it, to help design better vaccines.
2. To find out what factors in people influence how well they respond to the YF17D vaccine and how long their protection lasts.
3. To create clear and effective ways to share information about new vaccines.
By fostering partnerships across Europe and South America, Yellow4FLAVI accelerates data and sample sharing and strengthens responses to viral threats amplified by climate change. Ultimately, the project aims to provide robust scientific and societal foundations for future pandemic preparedness.
