Summary
ENT1DEP aims to define causal links between infections and NCDs by focusing on enterovirus (EV) infections and type 1 diabetes (T1D), a robust association without proof of causality. Causality is addressed by a multidisciplinary, multi-layer approach, using in-vitro and in-vivo models, unique human samples, and artificial intelligence to identify mechanisms and related biomarkers, asking 3 key questions:
1. Why are only insulin-producing β-cells destroyed by EVs? Weak β-cell antiviral responses and high expression of EV entry receptors may favour EV persistence. This hypothesis is addressed using human cell models (stem-cell-derived β/α-cells, organoids, their genetic modifications, anti-EV T-cells) and pancreas tissues from T1D patients.
2. Why do only some individuals develop T1D after EV infection? Weak EV immunity may predispose to virus spreading to pancreas, persistence and local inflammation, triggering autoimmunity. This hypothesis is addressed by analysing adaptive and innate immune responses to EVs, correlating these with gene polymorphisms and EV persistence in children followed from birth and who developed T1D.
3. How can EV-associated T1D risk be attenuated? By using vaccines inducing protective immunity and antiviral drugs eradicating persistent infection. This hypothesis is addressed by examining samples from pioneering EV vaccine and T1D antiviral trials to develop biomarkers of vaccine- vs infection-induced immunity as surrogates of vaccine efficacy; by studying whether vaccine-induced antibodies prevent EV-induced diabetes in mice; by correlating antiviral treatment with EV clearance and immunity to identify biomarkers for EV eradication and patient selection.
The final goal is to identify individuals at risk for EV-induced T1D as targets for early interventions. These outcomes may also facilitate progress in other NCDs extending impact. This new knowledge is disseminated among stakeholders to facilitate optimal NCD prevention and treatment.
1. Why are only insulin-producing β-cells destroyed by EVs? Weak β-cell antiviral responses and high expression of EV entry receptors may favour EV persistence. This hypothesis is addressed using human cell models (stem-cell-derived β/α-cells, organoids, their genetic modifications, anti-EV T-cells) and pancreas tissues from T1D patients.
2. Why do only some individuals develop T1D after EV infection? Weak EV immunity may predispose to virus spreading to pancreas, persistence and local inflammation, triggering autoimmunity. This hypothesis is addressed by analysing adaptive and innate immune responses to EVs, correlating these with gene polymorphisms and EV persistence in children followed from birth and who developed T1D.
3. How can EV-associated T1D risk be attenuated? By using vaccines inducing protective immunity and antiviral drugs eradicating persistent infection. This hypothesis is addressed by examining samples from pioneering EV vaccine and T1D antiviral trials to develop biomarkers of vaccine- vs infection-induced immunity as surrogates of vaccine efficacy; by studying whether vaccine-induced antibodies prevent EV-induced diabetes in mice; by correlating antiviral treatment with EV clearance and immunity to identify biomarkers for EV eradication and patient selection.
The final goal is to identify individuals at risk for EV-induced T1D as targets for early interventions. These outcomes may also facilitate progress in other NCDs extending impact. This new knowledge is disseminated among stakeholders to facilitate optimal NCD prevention and treatment.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101137457 |
| Start date: | 01-01-2024 |
| End date: | 31-12-2027 |
| Total budget - Public funding: | 7 144 790,00 Euro - 7 144 790,00 Euro |
Cordis data
Original description
ENT1DEP aims to define causal links between infections and NCDs by focusing on enterovirus (EV) infections and type 1 diabetes (T1D), a robust association without proof of causality. Causality is addressed by a multidisciplinary, multi-layer approach, using in-vitro and in-vivo models, unique human samples, and artificial intelligence to identify mechanisms and related biomarkers, asking 3 key questions:1. Why are only insulin-producing β-cells destroyed by EVs? Weak β-cell antiviral responses and high expression of EV entry receptors may favour EV persistence. This hypothesis is addressed using human cell models (stem-cell-derived β/α-cells, organoids, their genetic modifications, anti-EV T-cells) and pancreas tissues from T1D patients.
2. Why do only some individuals develop T1D after EV infection? Weak EV immunity may predispose to virus spreading to pancreas, persistence and local inflammation, triggering autoimmunity. This hypothesis is addressed by analysing adaptive and innate immune responses to EVs, correlating these with gene polymorphisms and EV persistence in children followed from birth and who developed T1D.
3. How can EV-associated T1D risk be attenuated? By using vaccines inducing protective immunity and antiviral drugs eradicating persistent infection. This hypothesis is addressed by examining samples from pioneering EV vaccine and T1D antiviral trials to develop biomarkers of vaccine- vs infection-induced immunity as surrogates of vaccine efficacy; by studying whether vaccine-induced antibodies prevent EV-induced diabetes in mice; by correlating antiviral treatment with EV clearance and immunity to identify biomarkers for EV eradication and patient selection.
The final goal is to identify individuals at risk for EV-induced T1D as targets for early interventions. These outcomes may also facilitate progress in other NCDs extending impact. This new knowledge is disseminated among stakeholders to facilitate optimal NCD prevention and treatment.
Status
SIGNEDCall topic
HORIZON-HLTH-2023-DISEASE-03-07Update Date
12-03-2024
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Organisations
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| TAMPEREEN KORKEAKOULUSAATIO SR (Coördinator)
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| EMPIRICA GESELLSCHAFT FUR KOMMUNIKATIONS UND TECHNOLOGIEFORSCHUNG MBH
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| HELSINGIN YLIOPISTO
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| INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
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| KAROLINSKA INSTITUTET
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| OSLO UNIVERSITETSSYKEHUS HF
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| PIRKANMAAN HYVINVOINTIALUE
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| SANOFI PASTEUR SA
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| TARTU ULIKOOL
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| THE WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH PUBLIC COMPANYLIMITED BY GUARANTEE
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| TURUN YLIOPISTO (UTU)
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| UNIVERSITY OF NEW SOUTH WALES
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| University of Oulu / Oulun yliopisto (UOULU)