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Immune profiling to guide host-directed interventions to cure HBV infections

Project description

Host-directed interventions to cure hepatitis B infections

The objective of the EU-funded IP-cure-B project is to develop novel curative concepts for chronic hepatitis B (CHB). The project aims to improve the cure rate of CHB by boosting innate immunity with immune modulators and stimulating adaptive immune responses with a novel therapeutic vaccine. Researchers will also identify immune and viral biomarkers for patient stratification and treatment response monitoring. Integration of biological and clinical data will enable models for the best combination treatment and effectiveness of novel curative therapies with respect to disease spectrum and patient heterogeneity. The preclinical platform will be evaluated in humanised mice, combining immune-modulatory strategies to stimulate innate immunity, rescue exhausted HBV-specific T cells and generate anti-HBV adaptive responses. Proof of concept will be obtained in a clinical trial of a combination of novel compounds stimulating innate immunity.

Objective

The objective of the project is to develop novel curative concepts for chronic hepatitis B (CHB). Specific aims will be to: 1) improve the rate of functional cure of CHB by boosting innate immunity with immune modulators and stimulating adaptive immune responses with a novel therapeutic vaccine; ii) characterize immune and viral biomarker signatures for patient stratification and treatment response monitoring; iii) integrate biological and clinical data to model the best combination treatment for future trials; iv) model the effectiveness of novel curative therapies with respect to disease spectrum, patient heterogeneity, and constraints of National Health Systems.

The project organization will combine: i) a Proof of Concept clinical trial of a combination of 2 novel compounds stimulating innate immunity; ii) a preclinical immune therapy platform in humanized mice combining immune-modulatory strategies to stimulate innate immunity, rescue exhausted HBV-specific T cells and generate anti-HBV adaptive responses; iii) extensive virologic and immune profiling to identify correlates of cure in patients, iv) the integration of large biological and clinical datasets, v) a cost-effectiveness modelling of new therapeutic interventions, vi) project management, vii) results exploitation and dissemination.

The proposal responds to the work program by: i) including the evaluation of emerging concepts in drug and vaccine development to discover a curative strategy for CHB, a major public health concern for Europe, ii) capitalizing on knowledge of host-pathogen interactions to develop novel immune-based therapies, iii) considering age, gender and viral genetic variations, iv) comprising a clinical trial and a pre-clinical platform for the discovery of novel immune interventions, and selection of relevant biomarkers for validation in established clinical cohorts, v) addressing conditions for effective uptake of the new curative interventions by National Health Systems.

Call for proposal

H2020-SC1-BHC-2018-2020

See other projects for this call

Sub call

H2020-SC1-2019-Two-Stage-RTD

Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution
€ 4 221 976,69
Address
RUE DE TOLBIAC 101
75654 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Links
Total cost
€ 4 324 130,69

Participants (15)