1. Perform a proof of concept clinical trial to evaluate novel immunomodulatory strategies to boost innate immunity and reshape the immune environment in the infected liver to enhance adaptive immunity in order to better respond to stimulation with a therapeutic vaccine;
2. Characterize immune and viral biomarkers and signatures in relevant clinical cohorts that will then be applied to stratify patients for treatment and monitor responses to host targeted therapies;
3. Design, produce and down-select the best DNA-Replicon (DREP)-based and dendritic cell (DC)-targeting HBC vaccines and their combinations that will be evaluated in double humanized HIS- HUHEP mouse model together with the same innate immunity boost before entering clinical trial evaluation;
4. Integrate biological and clinical data from mouse models and clinical studies with statistical approaches to model the best combination treatment for chronic hepatitis B (CHB) or future clinical trials;
5. Model the effectiveness of the novel cure therapy to tackle the whole spectrum of the disease and different patient populations, and promote an effective uptake by European and other international health systems.