The human immune system obviously possesses the capability to resolve an acute HBV infection in about 90% of infected adults. An effective virus-specific B- and T-cell response is regarded a key determinant of virus control and finally resolution of HBV infection. Unfortunately, B- and T-cell responses are hardly detected and functionally impaired in chronic HBV infection.
The mission of TherVacB is to overcome HBV-specific immune tolerance and to restore antiviral B-cell and T-cell responses by therapeutic vaccination to finally cure HBV.
Cutting-edge therapeutic vaccination technology – made in the EU
Therapeutic vaccination is a highly attractive concept to break immune tolerance in patients with chronic infections and to establish a finite, curative treatment for hepatitis B. The TherVacB vaccine is based on our mechanistic understanding of immune failure during chronic HBV infection that includes dysfunctional B- as well as CD4 and CD8 T-cell responses. We therefore believe that simultaneous activation of B- as well as CD4 and CD8 T-cell responses is needed to achieve immune control of HBV. This led to the systematic development and mechanism-based design of TherVacB as a heterologous prime-boost, pangenotypic, mosaic vaccine that targets all relevant HBV genotypes and has the potential to cure chronic HBV infection in >95% of individuals worldwide.
In two priming steps four weeks apart, particulate HBV surface and capsid antigens activate helper T-cells and B-cells that start to produce neutralizing antibodies to prevent further virus spread, and (cross)prime effector T cells. The MVA-HBVac vector boost following 4 weeks after the second prime immunization boosts a broad and multifunctional effector CD4 and CD8 T-cell response, that finally controls HBV.
The clinical trial evaluating TherVacB is designed as a randomized, single-blinded, multi-center phase 1/2 trial to assess safety and tolerability of the approach and to collect first efficacy data of the therapeutic hepatitis B vaccine candidate in chronic hepatitis B patients.
TherVacB provides a novel and affordable, curative treatment option for chronic hepatitis B for the large number of patients worldwide. In combination with the established prophylactic vaccination, raising awareness and hepatitis B screening programs, a curative treatment approach will be instrumental to meet the United Nations Sustainable Development Goal 3.3 to combat hepatitis B and D viral infection worldwide by 2030.
Patients are eagerly awaiting the clinical introduction of TherVacB in the EU. We will build a European hepatitis B patient registry to be able to select patients fulfilling the criteria for inclusion into the TherVacB clinical trial and other trials aiming at HBV cure. The ethics of patient recruitment via social media will be studied within the consortium because this allows to reach patient groups at need but not in regular medical care yet. The registry will be expanded to Tanzania where patients for the first time will have an option to receive treatment for hepatitis B. The prospect of a potential cure of chronic hepatitis B virus infections raises hopes of affected people for sustained health and a stop of being stigmatized – largely increasing the quality of life.
The TherVacB consortium is highly committed to an open data policy and will present its generated data after completion of the clinical trial at national and international meetings to physicians and to the patients’ community.
TherVacB is an EU-funded project lasting five years from January 2020 to December 2024. Recruitment of first patient into the clinical trial is envisaged to start by the middle of 2021. Including patient into our registries in Europe and Tanzania will start mid of 2020.
A first-in-men application of TherVacB to assess safety and tolerability in healthy volunteers is funded by other sources and will precede the EU-funded TherVacB trial in chronic hepatitis B patients.