The aim of WP1 is to guarantee full synergy and integration between HDM-FUN partners to provide added European value in advancing the state of the art in research on invasive fungal infections and to facilitate the following outcomes:

To ensure the scientific and technological quality of results (supported by the General Assembly, the Executive Board, and the Scientific Advisory Board).

This clinical trial aims to investigate and collect evidence whether administering recombinant Interferon gamma (IFN) to patients with candidemia has the potential to improve clinical outcome. The trial is designed as a randomized, double-blind, placebo-controlled phase II study of the safety and antifungal activity of subcutaneous recombinant Interferon-gamma 1b (rIFN-gamma 1b) in conjunction with standard antifungal therapy.

In addition, it is used to collect clinical samples needed to identifying prediction biomarkers of efficacy of immunotherapy which will be identified in WP5, 6, and 7.

This clinical trial aims to assess prospectively the incidence of IAA in the EORTC-negative subpopulation of critically ill influenza patients, in ICUs of 12 European hospitals over 4 influenza seasons. Clinical samples (blood, PBMCs, BALF) are collected and banked (WP4) for further analysis to predict host and pathogen risk factors in WP5-7.

We believe that one of the reasons why host directed medicine is in its infancy in infectious disease is because the kind of infrastructure needed to explore host directed medicine has not been well established for cohorts of patients with fungal infection. In order to assess host-pathogen factors that can be used to guide treatment and prophylaxis we need a solid infrastructure to process and store samples. Here we aim to establish a centralized biobank in which samples are stored and made available even after the end of this proposal. The experimental procedures for PBMC isolation and sample collection are standardized by SOPs and by training research personnel.

The general objective of this work package is to dissect the genetic architecture of antifungal immunity regulation using a combination of genomic and functional genomic approaches.

Specific objectives:

1. Characterization of transcriptional networks activated during IFI.
2. Discovery of genetic factors underlying IFI.
3. Functional testing of variants associated with susceptibility to IFI.

This work package deals with the discovery of genetic variants with regulatory potential (eQTLs) or impacting protein structure/function that influence the risk of IFI and response to immunotherapy. The overarching aim is the provision of a basic list of variants with prognostic/diagnostic potential for prediction or early identification of invasive fungal infection and/or impact on immunomodulatory interventions.

The general objective of this work package is to investigate (1) the microbiome, (2) the metabolome, (3) the fungal genome and (4) the fungal phenome of patients enrolled in WP2 and WP3 in order to identify novel biomarkers of susceptibility to fungal infection, antifungal therapy or host-directed therapy.

The general objective of this work package is to identify host pathogen factors that can guide host-directed medicine approaches in fungal infection by in-depth immunological and functional profiling and to use these data to develop a prototype for a point of care test.

The general objective of this work package is to provide dissemination of final results of HDM-FUN clinical studies beyond the project participants to the wider scientific community and potential users of results, in particular clinicians, pharmacologists, industry, other commercial players and policymakers, that can also contribute to the use of results for commercial purposes or in the European Union’s /global public policymaking platforms. Dissemination plans are carefully designed in order to guarantee also an effective communication of HDM-FUN results to patients suffering of fungal infections as well as to a wider public. Social scientific studies are undertaken throughout the project to assess and facilitate suitability, acceptability and adaptability of the interventions described in the proposal in daily clinical ICU practice.

Dissemination through training of key users of the results are also promoted to encourage young scientists’ active participation in research activities and their professional development.

This work package assures also that the project results are translated into clinical or diagnostic use and public health benefit, thus ensuring the implementation and exploitation of the project results.