While endemic to the tropics, flaviviruses like Zika, dengue, West Nile or yellow fever virus are re-emerging pathogens of global health concern. Climate change and urbanization have largely contributed to the dissemination of their mosquito vector and Europe has in recent years been regularly confronted with autochthonous cases. Few vaccines are licensed to prevent flavivirus disease, but the yellow fever 17D (YF17D) vaccine has a unique track record of efficiency and safety.Intriguingly, despite its success, how YF17D induces immunity remains poorly understood. The YELLOW4FLAVI consortium aims to fill the gaps in our understanding of the mechanism of action of this vaccine by linking the structure of the viral particle to the resulting host immune response, in order to learn about optimal vaccine design for flaviviruses in general. Since social acceptance of vaccines is critical for their success, we will also develop optimal communication methods. This will provide us with the tools to tailor vaccine design not only to achieve optimal immune protection, but also to facilitate actual implementation.
We are molecular and structural virologists, cell biologists, immunologists, computational scientists, clinicians, and social scientists assembled in a tight collaborative network. To pursue our goal of obtaining a blueprint for determinants of long-lasting immunity for flavivirus vaccine candidates, we will use cutting-edge technologies like cryo-EM, super resolution microscopy, spatial transcriptomics, high-dimensional spectral flowcytometry, single-cell RNA sequencing, advanced cell engineering, small animal models, and clinical studies. In a unique manner, the consortium thereby follows a thread of events from the early response at the site of vaccine injection to the population perception of vaccination, harnessing an enhanced understanding of one of the most successful vaccines of mankind for the development of novel lines of defense against new and old threats.
Omniscope Limited is involved in Work Package 3 (WP3), Work Package 6 (WP6), and Work Package 7 (WP7) of the Yellow4FLAVI project. In WP3, Omniscope leads Task 3.5, focusing on Deep Immune Repertoire Analysis to Correlate Protective Immunity, utilizing their osT/B (single-cell) and osTCR/BCR (single-molecule) sequencing technologies to generate an expanded dataset from vaccination samples and study T cell responses in hamster and NHP models. This involves analyzing human clinical cohort samples, NHP samples, and hamster samples, with the goal of identifying immunodominant epitopes and tracing the chain of events driving protective immune responses. Omniscope's advanced sequencing capabilities will provide high-resolution data crucial for refining vaccine designs and improving immune response predictions.