TherVacB Phase 1a
This study is a single-center, open-label, ascending dose Phase 1a trial to evaluate the safety and immunogenicity of a heterologous protein prime/MVA boost therapeutic hepatitis B vaccine.
This is a first-in-human study in healthy individuals without prior hepatitis B infection or hepatitis B immunization.
Chronic hepatitis B virus (HBV) infection affects 260 million people and causes 880,000 deaths per year, remaining the leading cause of liver-related death and prompting a WHO call for action to eliminate HBV as a public health threat. Achieving this goal requires increased vaccination efforts, diagnosis of unknown infection, and curative treatment. Antiviral therapy with nucleos(t)ide analogues (NUCs) is well tolerated, reduces liver inflammation and effectively suppresses the virus, but does not affect HBV persistence and leaves infected individuals at significant risk of developing hepatocellular carcinoma (HCC). (Functional) cure of HBV is defined as loss of circulating hepatitis B surface antigen (HBsAg). Cure rates are <1% per year with NUCs - a rate comparable to spontaneous clearance of the virus by the immune system. We lack a definitive, curative treatment that can overcome immune tolerance in chronic hepatitis B (CHB) and help prevent its sequelae. Since spontaneous cure is accompanied by immune reconstitution, activation of HBV-specific B- and T-cell immunity by therapeutic vaccination is a promising strategy to control and ultimately cure HBV infection.
TherVacB was developed as a pangenotypic heterologous prime-boost therapeutic vaccine regimen. Knowing that the priming step is essential for therapeutic success, the adjuvanted particulate surface antigen (HBsAg, HBV genotype A) and a particulate mosaic HBV core antigen (HBcoreAg, genotypes C and D) are combined for priming and a modified vaccinia ankara virus (MVA) vector is used to boost B and T cell responses.
The TherVacB Phase 1a trial is funded by Helmholtz Zentrum München and Fraunhofer Gesellschaft (P4/180-600369). TherVacB is an EU-project led by Helmholtz-Zentrum Munich and funded within the Horizon 2020 program of the European Commission. The UKE is the sponsor of this study and serves as a study site.
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