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In vivo electroporation improves therapeutic potency of a DNA vaccine targeting hepadnaviral proteins.

In vivo electroporation improves therapeutic potency of a DNA vaccine targeting hepadnaviral proteins.

Authors :
Khawaja G
Buronfosse T
Jamard C
Abdul F
Guerret S
Zoulim F
Luxembourg A
Hannaman D
Evans CF
Hartmann D
Cova L
Source :
Virology [Virology] 2012 Nov 10; Vol. 433 (1), pp. 192-202. Date of Electronic Publication: 2012 Aug 24.
Publication Year :
2012

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.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1096-0341
Volume :
433
Issue :
1
Database :
MEDLINE
Journal :
Virology
Publication Type :
Academic Journal
Accession number :
22921316
Full Text :
https://doi.org/10.1016/j.virol.2012.07.014