Yellow4FLAVI project and women’s leadership

Kelly Prifti, Project Manager – GO

In honor of the International Women’s Day, we’d like to give the spotlight to a strong female duo at Institut Pasteur:  Dr. Giovanna Barba-Spaeth, Coordinator of the Yellow4FLAVI Horizon Europe funded project and Head of the Flavimmunity Group, and Marine Hurard, European Project Manager at the Grants Office.

Dr. Giovanna Barba-Spaeth  

1. What is your background and current research focus?   

I am a molecular and structural virologist, and I have been working on Flaviviruses for more than 25 years. We focus on yellow fever virus, particularly the YFV17D live attenuated vaccine, as a model to understand the role of the flavivirus viral particle structure in virus entry, maturation and antigenicity.  

2. Tell us a bit about Yellow4FLAVI: how did it come to fruition and what are the main objectives?  

The YF17D vaccine is one of the most successful live attenuated vaccines available, able to induce long-lasting immunity after a single shot. Yellow4FLAVI wants to investigate the relationship between the shape of the vaccine viral particle and its immunogenicity. For that it will study the vaccine at three levels: 1) the virus particle: to understand the role of the virus structure on antigen processing and presentation of protective epitopes; 2) the host: to analyze the immune response after vaccination from the early events at the site of injection to the maturation of a long-lasting immunological memory; 3) the target population: to explore the concerns about vaccine acceptance and vaccine information at the population level.  

The project stems from a previous collaboration with colleagues from LMU Munich funded by an ANR-PRCI grant to study the immunogenicity of the yellow fever 17D vaccine. However, the ambition of Yellow4FLAVI is broader because in addition to studying the impact of the virus structure on immunogenicity, we are going to dissect the host response to the vaccine and the social aspects linked to vaccination.  

The consortium involves 13 laboratories in 7 countries with expertise including structural virology, cell biology, immunology, clinical and social studies and uses complementary approaches like cryo-EM, super resolution microscopy, spatial transcriptomic, computational modelling of cell-cell communication, small animal models and clinical studies.   

The goal is to obtain a blueprint for host determinants, inducers of long-lasting immunity and to provide a general model of antigen design for other flaviviruses vaccine candidates.  

3. Isn’t yellow fever a tropical disease? Why is this the focus of a European research project?  

Flaviviruses are usually endemic of the tropics, however, climate change and urbanization have rapidly contributed to the dissemination of their mosquito vector to Europe and some flaviviruses have become endemic in more temperate regions like, for example, West Nile or Usutu viruses in Italy or Greece. Others, like Zika or dengue, generate yearly increasing autochthonous cases and local outbreaks in countries like Spain, France or Italy. Thus, Flaviviruses are an upcoming threat to Europe. The specific call that funded Yellow4FLAVI was focusing on “Understanding vaccine-induced immunity” and since YF17D has a unique track record of efficiency and safety but remains poorly understood, our project proposes to fill the gaps in our understanding of the generation of long-lasting immunological memory.   

4. The yellow fever 17D (YF17D) vaccine has been widely used for over 80 years, yet how it induces immunity is still poorly understood. Why is that?  

We could say that YF17D has been the victim of its own success. Because of the high efficacy of the vaccine, yellow fever disease has been rapidly contained, and it was no longer considered a Public Health threat. This reduced considerably the research efforts done on yellow fever. Nevertheless, research on YF17D has progressed and system vaccinology studies in the early 2000s have shed light on the immune response to this vaccine underscoring an equally strong B and T cell response as the basis of YF17D efficacy. However, several aspects have not been studied in depth; because virus neutralization is mediated by antibodies (B cell response), the role of the T cell response is still quite unexplored as well as the local immune response in the skin. We will work on these aspects in this project.   

5. What are your hopes for the outcomes of this project?   

Our project proposes to study not “why” YF17D is an effective vaccine but “how” it achieves the stimulation of long-term immune memory. We propose that the conformation of the YF17D viral particle promotes the presentation of protective epitopes, and the spatial and temporal organization of the immune response and cell-cell communication at the injection site instructs the efficacy, quality and persistence of immunity to the vaccine. Since the structure of the viral particle is similar among Flaviviruses we could use the lessons learnt from YF17D to design vaccines for other viruses such as dengue, Zika or West Nile that replicate the features of YF17D.   

In addition, our consortium, grouping together different backgrounds (biologists, clinicians and social scientists), allows us to apply a multilevel approach enriched by mutual exchanges to increase our knowledge on vaccines and vaccine acceptance and to leverage our capacity to respond to new emerging threats. 

Ms. Marine Hurard   

1. Tell us about your background.  

My background is in Political Sciences and European Affairs, with Master’s degrees from Sciences Po and the College of Europe, and over 10 years of experience developing, coordinating, and managing EU health projects across various programmes. Before joining Pasteur last year, I worked with organisations such as AP-HP, the Medicen Paris Region health cluster, and an NGO, collaborating with clinicians, researchers, patient advocates, and healthcare authorities to advance health outcomes.   

2. What does your role Project Manager consist of?  

As Project Manager, I oversee project coordination, working closely with the scientific Coordinator to ensure smooth daily operations. I manage governance activities, such as Steering Committees and General Assemblies, and track Work Package (WP) progress to ensure timely delivery of project outputs with our WP Leads. I also serve as the main contact for partners, other Pasteur support services and the European Commission to address any concerns.  

In collaboration with our partners and Pasteur’s units, I handle budget tracking, reporting to the European Commission, and research data management, ensuring compliance with ethical, legal, and regulatory standards. Additionally, I lead communication and dissemination efforts, managing the website, social media content, and fostering partnerships.  

3. 13 partners in 7 countries, 6 clinical studies, 8 work packages and 58 deliverables: that’s a lot to keep track of! What are some of the tools and techniques you rely on to manage such a complex project?  

It requires a combination of structure, flexibility, and effective communication. Monthly online Steering Committee and WP meetings, as well as bi-annual General Assemblies, ensure alignment and allow us to address any issues promptly. Clear documentation and well-defined processes are also crucial. We rely on collaborative platforms such as Microsoft Teams and other tools to efficiently track progress. Maintaining strong relationships with our partners and involved stakeholders, including meeting face-to-face when possible, and anticipating challenges is key to keeping the project on track and meeting our goals.  

4. What do you like best about your job?  

I love the operational variety in my role, which keeps things dynamic and interesting. I enjoy collaborating with talented people from diverse backgrounds to advance science and improve health outcomes.