Periodic Reporting for period 2 - HORUS (Casting light on HOst-cytomegaloviRUs interaction in Solid organ transplantation)
Okres sprawozdawczy: 2024-05-01 do 2025-10-31
Solid organ transplantation (SOT) is the treatment of choice for end-stage organ failure, but the immunosuppressive drugs used to prevent graft rejection expose to an increased risk of new symptoms or the development of post-transplant disorders such as opportunistic infections. Cytomegalovirus (CMV) is the most frequent infectious complication following solid organ transplantation. CMV is responsible for infections that usually go unnoticed, even though it remains latent in the body for life when present. In a context of organ transplant patients, who are immunocompromised people, CMV can be dangerous.
CMV may occur as a primary infection in CMV-naïve patients after SOT, or it can be reactivation of latent donor or recipient infection in CMV-seropositive SOT recipients.
"HORUS" (Casting light on HOst-cytomegaloviRUs interaction in Solid organ transplantation) study is a European research project, funded by the European Commission (Horizon Europe) involving 24 partners in 7 European countries (France, Spain, Czech Republic, Belgium, Switzerland, Germany and Italy).
The aim of HORUS study is to build the first longitudinal cohort of European SOT recipients to investigate viral, clinical and immunological characteristics of the host-virus interactions in the transplant setting in 450 solid organ transplants (heart, lung kidney and liver). Combining those parameters in the first 100 patients of the cohort will provide:
- a signature early after transplantation to predict the risk of developing CMV infection
- a signature at day 0 of infection to predict the risk of CMV disease severity
Found signatures will be validated on the whole retrospective cohort and prospectively in a “proof-of-concept" study.
Moreover, HORUS will include functional in vitro and mouse models to investigate the mechanisms of lymphocyte response to CMV and provide innovative methods to increase CMV-specific immunity.
The goal is to determine which patients are the most at risk to develop CMV infections, based on their immune response. HORUS will lead to personalized clinical prevention and treatment of CMV disease and to improvement of patient outcomes.
CMV may occur as a primary infection in CMV-naïve patients after SOT, or it can be reactivation of latent donor or recipient infection in CMV-seropositive SOT recipients.
"HORUS" (Casting light on HOst-cytomegaloviRUs interaction in Solid organ transplantation) study is a European research project, funded by the European Commission (Horizon Europe) involving 24 partners in 7 European countries (France, Spain, Czech Republic, Belgium, Switzerland, Germany and Italy).
The aim of HORUS study is to build the first longitudinal cohort of European SOT recipients to investigate viral, clinical and immunological characteristics of the host-virus interactions in the transplant setting in 450 solid organ transplants (heart, lung kidney and liver). Combining those parameters in the first 100 patients of the cohort will provide:
- a signature early after transplantation to predict the risk of developing CMV infection
- a signature at day 0 of infection to predict the risk of CMV disease severity
Found signatures will be validated on the whole retrospective cohort and prospectively in a “proof-of-concept" study.
Moreover, HORUS will include functional in vitro and mouse models to investigate the mechanisms of lymphocyte response to CMV and provide innovative methods to increase CMV-specific immunity.
The goal is to determine which patients are the most at risk to develop CMV infections, based on their immune response. HORUS will lead to personalized clinical prevention and treatment of CMV disease and to improvement of patient outcomes.
For the WP1, patient recruitment progressed very strongly across all transplant cohorts, with heart transplant recruitment completed and only a limited number of kidney, liver and lung recipients remaining to reach targets. A total of 463 patients were included in cohort 1 (vs. 450 expected, including 28 additional kidney transplant recipients) and 235 patients in cohort 2 (vs. 150 expected). Clinical data collection and cohort management were implemented as planned, alongside sample logistics, with the first shipment of samples successfully completed (1,360 samples shipped) and further repatriations scheduled.
WP2 (R+) and WP3 (D+R-) implemented a common analytical strategy to assess the risk of CMV primo-infection, reactivation or superinfection after transplantation in the HORUS exploratory cohorts. Multiple analyses were performed, including ex vivo CMV detection by PCR on donor biopsies (WP3), Torque Teno Virus measurement, serology and neutralization assays (WP2 and WP3), with additional proteomic analyses conducted in WP3. Deep immune profiling of T and NK cells was achieved through harmonised flow cytometry, transcriptomic analyses and the initiation of integrated bioinformatic analyses, generating the first holistic datasets for R+ and R- transplant recipients.
WP4 focused on the pre-validation and harmonisation of ELISpot and flow cytometry assays across the three main laboratories (VHIR, USAAR and UBx) to ensure generation of comparable and robust data in order to validate our signatures obtained in WP2 and WP3 on our validation cohort obtained in WP1. Through joint meetings, shared training plans and on-site harmonisation sessions, common SOPs were reviewed, aligned and finalised, including agreement on equipment use, software, immune panels and workflows. A joint harmonisation session at VHIR in June 2025 successfully aligned key protocol parameters and analysis procedures, establishing a validated and shared framework for the implementation of WP4 experimental activities.
In WP5, in vitro experiments were initiated to assess the impact of different immunosuppressive drugs and preparations continued for murine in vivo models to evaluate immune modulation strategies, including mTOR inhibitors. Major progress was achieved with the HORUS-COPE clinical trial: the protocol and regulatory documents were submitted to Swiss Ethics in December 2025, with approvals and first patient inclusion expected in early 2026. Operational and trial preparation activities advanced as planned, positioning the study to start recruitment on schedule and to be completed within the overall project timeframe.
WP2 (R+) and WP3 (D+R-) implemented a common analytical strategy to assess the risk of CMV primo-infection, reactivation or superinfection after transplantation in the HORUS exploratory cohorts. Multiple analyses were performed, including ex vivo CMV detection by PCR on donor biopsies (WP3), Torque Teno Virus measurement, serology and neutralization assays (WP2 and WP3), with additional proteomic analyses conducted in WP3. Deep immune profiling of T and NK cells was achieved through harmonised flow cytometry, transcriptomic analyses and the initiation of integrated bioinformatic analyses, generating the first holistic datasets for R+ and R- transplant recipients.
WP4 focused on the pre-validation and harmonisation of ELISpot and flow cytometry assays across the three main laboratories (VHIR, USAAR and UBx) to ensure generation of comparable and robust data in order to validate our signatures obtained in WP2 and WP3 on our validation cohort obtained in WP1. Through joint meetings, shared training plans and on-site harmonisation sessions, common SOPs were reviewed, aligned and finalised, including agreement on equipment use, software, immune panels and workflows. A joint harmonisation session at VHIR in June 2025 successfully aligned key protocol parameters and analysis procedures, establishing a validated and shared framework for the implementation of WP4 experimental activities.
In WP5, in vitro experiments were initiated to assess the impact of different immunosuppressive drugs and preparations continued for murine in vivo models to evaluate immune modulation strategies, including mTOR inhibitors. Major progress was achieved with the HORUS-COPE clinical trial: the protocol and regulatory documents were submitted to Swiss Ethics in December 2025, with approvals and first patient inclusion expected in early 2026. Operational and trial preparation activities advanced as planned, positioning the study to start recruitment on schedule and to be completed within the overall project timeframe.