Objectives

• Identify virological, immunological and human genetic risk factors associated with severe flavivirus infections with a major focus on West Nile and Dengue virus.
• Dissect the humoral immune response against viral infections with a strong focus on mAbs selection and characterization.
• Define the phenotype and functional role of T-cell response in flavivirus infection and pathogenesis.
• Identify and characterise viral-host interactions for design & synthesis of host-viral protein inhibitors.
• Decipher 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.

Workplan

Organised into seven work packages (WPs) from which five (WP2, 3, 4, 5, 6) scientific, led by world-renowned expert in the respective field and two non-scientific (WP1,7) WPs.

 

• WP2 is focused on virological, immunological & human genetic risk factors of severe infections and is led by Prof. Shen-Ying Zhang (IMAGINE).
• WP3 dedicated to the dissection of the B cell response and selection of human monoclonal antibodies is led by Renata Grifantini, PhD (INGM).
• WP4 is led by Prof. Fausto Baldanti (IRCCS OSM), and it is devoted on the dissection of T-cell mediated response against Flaviviruses.
• WP5 is dedicated to virus-host interactions and drug development and is led by Nolwenn Jouvenet, PhD (IP).
• WP6 led by Ana Moreno Martin, PhD (IZSLER), is focused on Flaviviridae epidemiology in humans, animals, and environment for a 'One Health' approach.

 

The non-scientific work packages (WPs) focus on project management and coordination (WP1), which is led by Prof. Fausto Baldanti (IRCCS OSM), while WP7 addresses communication, dissemination, exploitation, and a One Health approach to pandemic preparedness, ensuring impact beyond the project’s lifetime, led by INN-ACTA.

Expected results, outcomes and impact

InFlame will:
• Characterize genetic, immunological and virological factors potentially associated with a higher rate of severe infection to improve the personalized management of infected patients.
• Understand immune responses related to protective memory response or induction of antibody-dependent enhancement of infection.
• Identify new neutralising anti-Dengue virus and West Nile Virus monoclonal antibodies and drugs with preclinical evidence of efficacy, small library of new lead drugs to inhibit host-virus adhesion/infection.
• Identify vector-related and climate-associated factors able to impact on the flavivirus epidemiology and pandemic risk.

 

Outcomes:
• Clinicians will apply new screening assays for identifying high-risk patients.
• The development of innovative therapeutic tools to combat severe diseases will benefit patients, society, and healthcare, boost the EU economy, and stimulate the pharmaceutical and biotechnology industries to develop new monoclonal antibodies and drugs.
• Gaining insight into the factors that contribute to protective immunity will be an advantage for the scientific community.
• Raising awareness of pandemic risks, the link between outbreaks and climate change, and the One Health concept is essential for the public and authorities.

 

Impacts:
• Scientific: Breakthrough scientific discovery on Dengue and West Nile Virus infections.
• Social and Economic: Reduction of infection spread and severe disease leads to lower healthcare costs, improved preparedness for outbreaks, and greater social awareness of infections.