Yellow4FLAVI at Mid-Term: Key Scientific Advances

By Marine Hurard, European Project Manager – GO 

Since 2024, the Institut Pasteur is coordinating Yellow4FLAVI, a five-year Horizon Europe research project funded by the European Union and supported by the Grants Office, alongside key support services including legal and financial teams.  

Coordinated by Dr. Giovanna Barba-Spaeth with Project Manager Marine Hurard, the consortium brings together 15 partners from 8 countries across the EU and Colombia. Flaviviruses such as Zika, dengue, West Nile, and yellow fever are re-emerging pathogens of global health concern. Yellow4FLAVI leverages the highly successful yellow fever 17D vaccine as a model to deepen our understanding of flavivirus immunity and inform the design of novel vaccine candidates, while also developing evidence-based communication strategies to support vaccine acceptance with a dedicated social sciences work package.

Yellow4FLAVI has achieved significant results at mid-term, marked by high-impact publications, key social science findings, and a successful mid-term meeting in Padua, Italy.  

Scientific Highlights 

Research teams have made significant advances in understanding flavivirus vaccine immunology. Santos-Peral et al. (Nature Communications, 2024) demonstrated that individuals with prior flavivirus immunity mount a yellow fever vaccine response skewed toward cross-reactive antibodies — antibodies that could potentially enhance dengue virus infection rather than neutralise it. This finding raises important safety considerations for vaccination strategies in flavivirus-endemic regions where sequential exposures are common. 

A companion study (Cell Reports Medicine, 2025) by the same group revealed that basal T cell activation levels — reflecting the baseline immune tone of an individual — can predict the magnitude of the yellow fever vaccine response, independently of cytomegalovirus serostatus or biological sex. This opens new avenues for personalised vaccination approaches. Complementing these findings, Winheim et al. (PNAS, 2025) showed that early interferon-driven activation of dendritic cells and monocytes following yellow fever vaccination is a strong correlate of subsequent antibody responses, shedding new light on the innate-adaptive immune axis in vaccine immunogenicity. 

At the cellular memory level, Frischholz et al. (Nature Immunology, 2026) uncovered a key mechanism: naive-like memory T cells enter a state of metabolic quiescence that both precedes and sustains long-term antigen-specific T cell memory — a fundamental discovery with broad implications for durable vaccine-induced protection. 

On the vaccine development front, Ma et al. (Nature Communications, 2025) reported encouraging immunological and transcriptomic profiles for a chimeric live-attenuated Zika vaccine candidate, providing a strong preclinical rationale for further development. Meanwhile, Dallmeier & Alpizar (IJID, 2025) proposed a rationalised framework for assessing and mitigating the risks associated with live-attenuated dengue vaccines, contributing to the field's ongoing safety debate. New tools to analyze the immune response to flavivirus infection or vaccination based on the design of epitope-focused antigens have been generated for yellow fever (Nat.Comm. 2024) and dengue (mSphere 2025).  

Social Sciences Insights 

Qualitative research conducted through focus group discussions and in-depth interviews with members of the general public in Germany and Colombia is generating preliminary findings into public perceptions of vaccines and vaccination. These preliminary findings suggest that the COVID-19 pandemic may have had a lasting influence on attitudes toward novel vaccines, touching on questions of institutional trust, approval processes, and safety communication. Early observations also suggest that perceived disease severity and concerns about adverse effects may play a stronger role in vaccine decision-making than individuals' understanding of immunity itself. Country-specific differences in the role of trusted intermediaries — such as healthcare providers and community leaders — are also emerging as potentially relevant considerations. Based on these preliminary findings, initial suggestions point toward the importance of transparent communication around adverse effects and approval processes, and the active engagement of trusted healthcare intermediaries in vaccination campaigns. These insights will inform the development of tailored risk communication strategies for flavivirus vaccines in subsequent phases of the project. 

Mid-Term Meeting, Padua 

In May, 50 participants from 11 countries (including 5 SAB members) gathered for the General Assembly and a training workshop on science communication, popularization, and storytelling. With scientific presentations, early-career researcher pitch sessions, parallel Work Package and inter-WP meetings, a Scientific Advisory Board panel, and forward-looking discussions on AI in vaccinology and PhD career development, the meeting was a resounding success. A rich social programme of cultural visits and networking opportunities further strengthened cohesion across the consortium, confirming the project's strong scientific momentum and collaborative spirit as it enters its second and decisive phase. 

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