title: In vivo electroporation improves therapeutic potency of a DNA vaccine targeting hepadnaviral proteins.
abstract: This preclinical study investigated the therapeutic efficacy of electroporation (EP)-based delivery of plasmid DNA (pDNA) encoding viral proteins (envelope, core) and IFN-γ in the duck model of chronic hepatitis B virus (DHBV) infection. Importantly, only DNA EP-therapy resulted in a significant decrease in mean viremia titers and in intrahepatic covalently closed circular DNA (cccDNA) levels in chronic DHBV-carrier animals, compared with standard needle pDNA injection (SI). In addition, DNA EP-therapy stimulated in all virus-carriers a humoral response to DHBV preS protein, recognizing a broader range of major antigenic regions, including neutralizing epitopes, compared with SI. DNA EP-therapy led also to significant higher intrahepatic IFN-γ RNA levels in DHBV-carriers compared to other groups, in the absence of adverse effects. We provide the first evidence on DNA EP-therapy benefit in terms of hepadnaviral infection clearance and break of immune tolerance in virus-carriers, supporting its clinical application for chronic hepatitis B.
authors.affiliation: Université Lyon1, France.
authors.forename: Ghada
authors.initials: G
authors.lastname: Khawaja
authors.forename: Thierry
authors.initials: T
authors.lastname: Buronfosse
authors.forename: Catherine
authors.initials: C
authors.lastname: Jamard
authors.forename: Fabien
authors.initials: F
authors.lastname: Abdul
authors.forename: Sylviane
authors.initials: S
authors.lastname: Guerret
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.forename: Alain
authors.initials: A
authors.lastname: Luxembourg
authors.forename: Drew
authors.initials: D
authors.lastname: Hannaman
authors.forename: Claire F
authors.initials: CF
authors.lastname: Evans
authors.forename: Daniel
authors.initials: D
authors.lastname: Hartmann
authors.forename: Lucyna
authors.initials: L
authors.lastname: Cova
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D002908:Chronic Disease; D004270:DNA, Circular / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004372:Ducks; D018274:Electroporation; D000939:Epitopes; D018347:Hepadnaviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary* / Q000821:virology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology; D015611:Hepatitis B Virus, Duck / Q000276:immunology*; D006524:Hepatitis, Viral, Animal / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D007108:Immune Tolerance; D056724:Immunity, Humoral; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D010957:Plasmids; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D004270:DNA, Circular; D000939:Epitopes; D017325:Hepatitis B Vaccines; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; D007371:Interferon-gamma