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: Ghada Khawaja, Thierry Buronfosse, Catherine Jamard, Fabien Abdul, Sylviane Guerret, Fabien Zoulim, Alain Luxembourg, Drew Hannaman, Claire F Evans, Daniel Hartmann, Lucyna Cova
• Journal: Virology (Virology) Vol. 433 Issue 1 Pg. 192-202 (Nov 10 2012) ISSN: 1096-0341 [Electronic] United States
• PMID: 22921316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Viral
• DNA, Circular
• Epitopes
• Hepatitis B Vaccines
• Vaccines, DNA
• Viral Core Proteins
• Viral Envelope Proteins
• Interferon-gamma

Topics

• Animals
• Antibodies, Viral (biosynthesis, immunology)
• Chronic Disease
• DNA, Circular (genetics, immunology)
• Disease Models, Animal
• Ducks
• Electroporation
• Epitopes
• Hepadnaviridae Infections (immunology, prevention & control, veterinary, virology)
• Hepatitis B Vaccines (administration & dosage, immunology)
• Hepatitis B Virus, Duck (immunology)
• Hepatitis, Viral, Animal (immunology, prevention & control, virology)
• Immune Tolerance
• Immunity, Humoral
• Interferon-gamma (biosynthesis, immunology)
• Plasmids
• Vaccines, DNA (administration & dosage, immunology)
• Viral Core Proteins (genetics, immunology)
• Viral Envelope Proteins (genetics, immunology)
• Viremia (immunology, prevention & control, veterinary, virology)