SHIELD

Deconstructing the protective immunity of yellow fever virus 17D to inform flavivirus vaccine design

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. Yellow4FLAVI 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.

The project is funded by the European Union under the call: HORIZON-HLTH-2023-DISEASE-03-17.

Yellow4Flavi Website

Evolvable and Rapidly Adaptable Monobodies: a broad-spectrum antiviral platform

EvaMobs is developing a rapid, flexible antiviral platform using evolvable monobodies (Mobs), small, human-derived proteins engineered to bind and inactivate viruses. Mobs are smaller than monoclonal antibodies, allowing for lower dosages, and, being derived from a human protein, are less likely to trigger an immune response. By combining computational design, pre-clinical and clinical validation, EvaMobs aims to rapidly identify potent antivirals. The platform will first target Influenza A, SARS-CoV-2, RSV, and Zika virus. This adaptable technology can address a wide range of viral threats, strengthening the EU’s pandemic preparedness. The consortium comprises 11 partners from 7 EU countries + Switzerland, and the project has received ~ 9 M€ funding from the European Health and Digital Executive Agency.

The project is funded by the European Union under the call: HORIZON-HLTH-2023-DISEASE-03-O4.

EvaMobs Website

IDEntification oF novel viral Entry factors aNd DevelopmEnt of antiviRal approaches

The project aims to adopt a comprehensive and integrative platform approach moving beyond virus-centric or single-gene methodologies, and applicable to a wide range of (re-) emerging viruses. Our pipeline focuses on preventing virus entry through a host bottom-up functional genetic approach in parallel to a virus top-down glycoprotein-centered approach. On the host side, we will identify novel virus entry factors, including attachment factors and proteins involved in endosomal uptake and virus genome uncoating, while on the virus side, we will use virus glycoproteins to identify novel epitopes and broadly neutralizing nanobodies that block virus attachment and membrane fusion. By combining these approaches, DEFENDER will systematically identify and characterize novel vulnerable virus-host interaction sites laying the groundwork for new antivirals and immunogens.

The project is funded by the European Union under the call: HORIZON-HLTH-2024-DISEASE-08-20.

DEFENDER Website

Targeting ER Import and Activation of Viral Glycoproteins: Towards Broad-Spectrum Antivirals

The EU research consortium VIGILANT is developing broad-spectrum drugs targeting viruses with pandemic potential. Coordinated by the German Primate Center – Leibniz Institute for Primate Research, the project is funded by the EU with approximately 7.5 million euros over four years.

The goal of VIGILANT is to develop compounds that are effective against a wide range of viruses and thus contribute to combating future pandemic threats. These compounds are designed to specifically block the transport of viral envelope proteins into the endoplasmic reticulum of infected cells, as well as their subsequent activation by host cell enzymes. The efficacy and safety of the candidate compounds will be tested in cell culture models and animal studies.

The project is funded by the European Union under the call: HORIZON-HLTH-2024-DISEASE-08-20.

VIGILANT Website

Comparative Signature of Marburg Virus Cell Activation as a Blueprint for the Identification of Antiviral Targets against Newly Emerging Viruses

The COMBINE project aims to advance our understanding of virus-cell entry by focusing on the critical early steps of infection, using Marburg virus (MARV) as a model. COMBINE applies an integrative experimental platform to dissect virus-cell binding, distinguishing initial attachment from cellular activation and internalisation. The project will identify key host factors, including tissue-specific attachment factors and functional receptors involved in MARV entry, as well as the cellular pathways governing virus uptake. In parallel, advanced proteomics, imaging and multi-omics approaches will characterise virus-host interaction signatures. By combining these strategies, COMBINE will not only deepen our understanding of MARV infection biology but also establish a technology pipeline that can be rapidly adapted to newly emerging viruses – thereby strengthening pandemic preparedness.

The project is funded by the European Union under the call: HORIZON-HLTH-2024-DISEASE-08-20.

COMBINE Website

Advancing Pandemic Preparedness: Innovative Multidisciplinary Strategies for COMBATing Severe Dengue

The COMBAT project aims to define the mechanisms driving severe dengue outcomes by integrating host immunometabolic and neuroimmune profiling with viral strain–specific analyses. Using patient-derived data, advanced multi-omics technologies, and physiologically relevant infection models, including brain organoids, COMBAT will dissect how viral diversity and host metabolic–immune dysregulation converge to promote severe disease. By combining experimental BSL-3 platforms like super resolution microscopy (SRM) and organ-on-chip, spatial-omics with advanced computational modeling, the project seeks to identify critical host–virus interaction nodes that enable predictive biomarkers and host-directed therapeutic strategies applicable to dengue and other emerging viral infections.

The project is funded by the European Union under the call: HORIZON-HLTH-2024-DISEASE-08-20.

COMBAT Website

Receptor-Focused Interventions Against Orthoflavivirus Neuroinvasion and Entry

REFINE is a collaboration between 4 European and 2 Australian partners that aims to enhance treatments for mosquito-borne orthoflavivirus infections by identifying new targets for antibodies, inhibitors, and vaccines. In addition, we will develop a platform to test the safety and effectiveness of these treatments before clinical trials.

The project is funded by the European Union under the call: HORIZON-HLTH-2024-DISEASE-08-20.

REFINE Website

Counter-acting the pandemic potential of flaviviruses: addressing virus-host interactions and defense strategies to design new therapeutics against WNV and DENV

The consortium of InFlaMe includes 11 partners from 5 countries, bringing together epidemiologists, virologists, immunologists, and climate change specialists to investigate the molecular mechanisms of Dengue virus (DENV) and West Nile Virus (WNV) infections. The goal is to accelerate antiviral discovery, identify new treatment compounds, and develop effective differential diagnoses. 

The main objectives comprise (i) identification of virological, immunological and human genetic risk factors associated with severe flavivirus infections, with a major focus on DENV and WNV; (ii) dissection of the humoral immune response against viral infections with a strong focus on monoclonal antibodies (mAbs) selection and characterization; (iii) definition of the phenotype and functional role of T-cell response in flavivirus infection and pathogenesis; (iv) identification and characterisation of viral-host interactions for design & synthesis of host-viral protein inhibitors and (v) deciphering the impact of climate changes and vector capacity on flavivirus epidemiology in human and animal settings for a “One Health” approach of surveillance and emergency planning.

The project is funded by the European Union under the call: HORIZON-HLTH-2024-DISEASE-08-20.

InFlaMe Website