Periodic Reporting for period 3 - HDM-FUN (Host directed medicine in invasive fungal infection)
Periodo di rendicontazione: 2023-01-01 al 2024-06-30
Despite novel treatment options and diagnostic tools, invasive fungal infections are still associated with an unacceptably high mortality and morbidity. Experts believe that a host-directed approach is needed to overcome this clinical challenge. No study to date in invasive fungal infection has integrated a host-directed strategy into a clinical trial. This consortium proposes for the first time a trans-disciplinary approach to identify personalized therapeutic and prophylactic strategies based on host-pathogen factors. We believe that we need such a personalized medicine approach in order to advance the aim of improved outcome in invasive fungal infection, and that, together with the exponential knowledge that has been gained in host-fungal interaction over the last two decades, it is time to move towards proof-of-principle clinical trials that can save lives of patients.
To this aim two clinical trials of host-directed medicine approaches will be performed: an immunotherapy trial with interferon gamma (IFNγ in patients with candidemia and a prospective observational trial in patients with influenza to identify patients at risk for aspergillosis that might benefit from antifungal prophylaxis.
To this aim two clinical trials of host-directed medicine approaches will be performed: an immunotherapy trial with interferon gamma (IFNγ in patients with candidemia and a prospective observational trial in patients with influenza to identify patients at risk for aspergillosis that might benefit from antifungal prophylaxis.
Both trials are open for recruitment. Overall, the third reporting period has focused on several key objectives and actions. Namely, in WP2 we have expanded the sites for the candidemia trial by collaboration with the ImmunoSep consortium and now all new sites in Greece are open for recruitment. The protocol for the candidemia trial has been revised and amended. In WP3, 13 sites have been opened for inclusion. Prospective samples have been collected in the last 2 influenza seasons and provided WP5,6,7 the possibility to explore host-pathogen factors. This has already provided insight that is useful for aims and deliverables defined by the consortium. The WP4 centralized biobank in Nijmegen has received samples and the routes and logistics for handling these samples from clinical trial centres have been established and are functional. Fungal collection biobanking is organised and include aspergillus and candidemia strains. Partners involved in WP5,6,7 have performed analysis and experiments in retrospective and prospectively collected samples. WP5 has identified novel genetic host-pathogen factors that associate with IAPA and might provide a rationale for designing prophylactic studies in patients with Influenza. WP6 has brought a novel concept in fungal immunology and pathogenesis of disease associated with fungi, namely the metabolic cross-talk between humans and fungi that might lead to novel diagnostic and therapeutic strategies. WP7 has explored host pathogen factors that can guide host-directed medicine approaches in fungal infection by in-depth immunological and functional profiling. We have also explored a lateral flow immunoassay for potential biomarkers.
Social scientists have performed interviews and were able to identify key aspects that will be useful for the implementation of immunotherapy in the clinics (WP8). Besides, we have continued to communicate project activities and also raising awareness about novel treatments in fungi infections in the scientific community and general public. A symposium has been organised in Greece in May 2024 with other two EU projects ( ImmunoSep, and HAP2) on immunotherapy for infection. A workshop at NIH has been organised in May 2024 named “Realising the Promise of Adjunctive Immune Therapy for Invasive Fungal Infections”.The HDM-FUN project was discussed, and US experts were invited to comment and to join this initiative. The project was well received, and the consensus was that the approach taken in HDM-FUN should also be implemented in US. The mycosis study group (MSG) was interested as well as other groups that would like to join the trials performed in HDM-FUN. A society, Immunotherapy for Fungal Infection Society, was founded to bring immunotherapy for fungal infection to the clinics. This has been made possible by the HDM-FUN project and will continue to have impact in the field of Immunotherapy for Infectious Disease.
Social scientists have performed interviews and were able to identify key aspects that will be useful for the implementation of immunotherapy in the clinics (WP8). Besides, we have continued to communicate project activities and also raising awareness about novel treatments in fungi infections in the scientific community and general public. A symposium has been organised in Greece in May 2024 with other two EU projects ( ImmunoSep, and HAP2) on immunotherapy for infection. A workshop at NIH has been organised in May 2024 named “Realising the Promise of Adjunctive Immune Therapy for Invasive Fungal Infections”.The HDM-FUN project was discussed, and US experts were invited to comment and to join this initiative. The project was well received, and the consensus was that the approach taken in HDM-FUN should also be implemented in US. The mycosis study group (MSG) was interested as well as other groups that would like to join the trials performed in HDM-FUN. A society, Immunotherapy for Fungal Infection Society, was founded to bring immunotherapy for fungal infection to the clinics. This has been made possible by the HDM-FUN project and will continue to have impact in the field of Immunotherapy for Infectious Disease.
HDM-FUN is a unique project with the ambition to change treatment of fungal infection and influence daily clinical practice. It has the ambitious goal of introducing a new paradigm in host-directed medicine, namely the personalization of treatment and prevention of fungal infections by stratification based on host and pathogen factors. At this moment, all clinical trials on immunotherapy in infectious diseases have had a ‘one size fits all’ approach. Because the immune status of ICU patients is substantially different, such an approach is eventually deemed to fail. HDM-FUN has setup its design of clinical trials and research in such a way that we will be able to overcome this hurdle after completion of the current proposal.
HDM-FUN will contribute to (i) creating societal impact by changing clinical practice to better control infectious diseases and reduce their burden, thereby ensuring health and well-being for all, at every stage of life; (ii) reducing antimicrobial resistance; and (iii) developing HPF-based targeted treatments and preventive measures, HPF-biomarker based diagnostics and novel standards with respect to clinical trials and protocols.
HDM-FUN will contribute to (i) creating societal impact by changing clinical practice to better control infectious diseases and reduce their burden, thereby ensuring health and well-being for all, at every stage of life; (ii) reducing antimicrobial resistance; and (iii) developing HPF-based targeted treatments and preventive measures, HPF-biomarker based diagnostics and novel standards with respect to clinical trials and protocols.