Immunology of HDV Infection

Institute of Virology, University Clinic Essen, Hufelandstrasse 55,

45122 Essen, Germany

[email protected]

1 Introduction 188

2 Natural History of the Clinical Course of HDV Infection 189

3 Immunopathogenesis 190

3.1 Is HDV a Cytopathic Virus? 190

3.2 B-Cell Immune Response 191

3.2.1 RoleofIgM Anti-HDV 191

3.3 T-Cell Immune Responses 192

3.3.1 T-Helper Cells 192

3.3.2 Cytotoxic T Cells 193

3.3.3 T-Cell Immune Responses After Immunization of Mice or Woodchucks . . 194

4 Vaccination Studies 195

4.1 Immunization with HDV Protein 198

4.2 Immunization with Synthetic Peptides 200

4.3 DNA Immunization 200

4.4 Immunization with Vaccinia Virus Expressing HDAg 201

4.5 HDV Is a Poor Immunogenic Protein 202

4.6 Conclusions on Vaccination Studies 202

5 Immunogenic Domains of HDAg 203

6 Closing Notes 205

References 205

Abstract Hepatitis delta virus (HDV) infection may occur as coinfection with hepatitis B virus (HBV) or as superinfection of a chronically HBV-infected patient. A strong antibody response is mounted, which persists for many years; however, it is not able to modulate the course of infection. In most cases the superinfection takes a chronic course. In patients with inactive disease (HDV PCR negative) an oligospecific T-helper cell immune response and a cytotoxic T-cell response were found, which were absent in patients with persistent viremia. The role of the cellular immune response in liver injury during acute infection has not been investigated. Vaccination strategies tested in the woodchuck model induced specific B- and T-cell responses but failed to protect from HDV infection.

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