MVA-HBVac-A novel vaccine vector that allows pan-genotypic targeting of hepatitis B virus by therapeutic vaccination.

Therapeutic vaccination holds the promise to cure chronic hepatitis B virus (HBV) infection. We hypothesize that B cell, CD4, and CD8 T cell responses are necessary to overcome HBV-specific immune tolerance in chronic infection because they accompany the rare, spontaneous resolution of chronic HBV infection. Therefore, we designed the heterologous prime-boost vaccine in which virus-like particle vaccination stimulates B and helper CD4 T cells and primes cytotoxic effector CD8 T cells and a vector boost expands the T cell response.

Scientific and medical evidence informing expansion of hepatitis B treatment guidelines.

Chronic hepatitis B treatment relies on nucleoside or nucleotide analogue drugs that suppress hepatitis B virus (HBV) replication, normalise liver enzymes, and slow disease progression with excellent safety profiles. Treatment is not curative, and patients remain at risk of cirrhosis and hepatocellular carcinoma. Treatment guidelines have generally restricted antiviral therapy to individuals with high HBV DNA and elevated ALT or hepatic fibrosis, often requiring longitudinal testing that can be scarcely available in resource-limited settings.

Efficient stabilization of therapeutic hepatitis B vaccine components by amino-acid formulation maintains its potential to break immune tolerance.

Background & Aims: Induction of potent, HBV-specific immune responses is crucial to control and finally cure HBV. The therapeutic hepatitis B vaccine combines protein priming with a Modified Vaccinia virus Ankara (MVA)-vector boost to break immune tolerance in chronic HBV infection. Particulate protein and vector vaccine components, however, require a constant cooling chain for storage and transport, posing logistic and financial challenges to vaccine applications.

Activation of CD4 T cells during prime immunization determines the success of a therapeutic hepatitis B vaccine in HBV-carrier mouse models.

Background & Aims: We recently developed a heterologous therapeutic vaccination scheme (TherVacB) comprising a particulate protein prime followed by a modified vaccinia-virus Ankara (MVA)-vector boost for the treatment of HBV. However, the key determinants required to overcome HBV-specific immune tolerance remain unclear. Herein, we aimed to study new combination adjuvants and unravel factors that are essential for the antiviral efficacy of TherVacB.