Spontaneous resolution of hepatitis b virus (HBV) infection is characterised by neutralising antibodies and HBV-specific T cell responses, elements which are lacking in chronic HBV infection. The EU-funded TherVacB project aims to overcome immune tolerance in chronic HBV infection and the virus’s resistance to cure. The interdisciplinary consortium will employ a heterologous prime-boost therapeutic vaccination scheme with proven efficacy in preclinical models of hepatitis B to target and activate B and T cell responses; thereby, TherVacB hopes to produce vaccine components and prepare a first-in-human application. To provide a clinical proof of concept of the therapeutic hepatitis B vaccine in patients with chronic hepatitis B, the consortium will establish a patient registry and perform a multicentre phase Ib/IIa clinical trial of the vaccine's safety and potency to induce immune control of chronic HBV infection.