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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Viral / biosynthesis
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Antibodies, Viral / immunology
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Chronic Disease
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DNA, Circular / genetics
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DNA, Circular / immunology
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Disease Models, Animal
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Ducks
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Electroporation
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Epitopes
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Hepadnaviridae Infections / immunology
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Hepadnaviridae Infections / prevention & control
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Hepadnaviridae Infections / veterinary*
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Hepadnaviridae Infections / virology
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Hepatitis B Vaccines / administration & dosage*
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Hepatitis B Vaccines / immunology
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Hepatitis B Virus, Duck / immunology*
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Hepatitis, Viral, Animal / immunology
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Hepatitis, Viral, Animal / prevention & control*
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Hepatitis, Viral, Animal / virology
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Immune Tolerance
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Immunity, Humoral
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Interferon-gamma / biosynthesis
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Interferon-gamma / immunology
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Plasmids
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Vaccines, DNA / administration & dosage*
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Vaccines, DNA / immunology
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Viral Core Proteins / genetics
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Viral Core Proteins / immunology*
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / immunology*
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Viremia / immunology
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Viremia / prevention & control
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Viremia / veterinary
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Viremia / virology
Substances
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Antibodies, Viral
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DNA, Circular
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Epitopes
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Hepatitis B Vaccines
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Vaccines, DNA
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Viral Core Proteins
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Viral Envelope Proteins
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Interferon-gamma