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Prophylactic vaccination against hepatitis D virus superinfection: from fiction to reality?
  1. Julia Lang-Meli,
  2. Christoph Neumann-Haefelin
  1. Department of Medicine II, University of Freiburg Faculty of Medicine, Freiburg, Germany
  1. Correspondence to Dr Christoph Neumann-Haefelin, Department of Medicine II, University of Freiburg Faculty of Medicine, Freiburg, Baden-Württemberg, Germany; christoph{at}

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Approximately 250 million people worldwide are chronically infected with hepatitis B virus (HBV). Nucleos(t)ide analogues (NAs) as the mainstay of antiviral therapy efficiently suppress viraemia, normalise liver enzymes and prevent progression of liver disease, however, they do not reduce hepatitis B surface antigen (HBsAg) levels in the majority of patients. HBsAg is an important component of the HBV satellite virus hepatitis D virus (HDV). It allows HBV and HDV viral entry through the interaction of its preS1 domain with the cell receptor sodium taurocholate cotransporting polypeptide (NTCP). Irrespective of antiviral treatment, patients with chronic HBV infection are thus at persistent risk of HDV superinfection. HDV superinfection leads to chronic HBV/HDV infection in the majority of patients and is associated with fast progression to liver cirrhosis.1 Even after the conditional approval of the HBV/HDV entry inhibitor bulevirtide (BLV) in Europe in 2020, treatment options for HBV/HDV infection are limited: NAs are not effective against HDV, (pegylated) interferon-alfa leads to sustained HDV elimination in <30% of patients, and BLV requires long-term treatment of so far not defined duration and fails in a substantial number of patients. Vaccination against HBV protects HBV-naïve individuals also against HDV infection, however, there is no vaccine that protects HBV-infected individuals against HDV superinfection. The development of a prophylactic vaccine that protects HBV-infected individuals against HDV superinfection is thus a high medical need. So far, all experimental HDV vaccines based on the hepatitis delta antigen (HDAg) in the form of peptides, protein, DNA or viral vectors failed in mouse or woodchuck models of HBV/HDV superinfection. Indeed, …

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  • Contributors JL-M and CN-H wrote the manuscript and drafted the figure.

  • Funding JL-M is supported by the Deutsche Forschungsgemeinschaft (IMM-PACT Programme of the Faculty of Medicine, University of Freiburg; Project number 413517907). The research of CN-H is funded by the Deutsche Forschungsgemeinschaft (TRR-179; project number 272983813).

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

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