In vivo infectivity of liver extracts after resolution of hepadnaviral infection following therapy associating DNA vaccine and cytokine genes.


:DNA-based vaccination appears of promise for chronic hepatitis B immunotherapy, although there is an urgent need to increase its efficacy. In this preclinical study, we evaluated the therapeutic benefit of cytokine (IL-2, IFN-γ) genes co-delivery with DNA vaccine targeting hepadnaviral proteins in the chronic duck hepatitis B virus (DHBV) infection model. Then, we investigated the persistence of replication-competent virus in the livers of apparently resolved animals. DHBV carriers received four injections of plasmids encoding DHBV envelope and core alone or co-delivered with duck IL-2 (DuIL-2) or duck IFN-γ (DuIFN-γ) plasmids. After long-term (8 months) follow-up, viral covalently closed circular (ccc) DNA was analysed in duck necropsy liver samples. Liver homogenates were also tested for in vivo infectivity in neonatal ducklings. Co-delivery of DuIFN-γ resulted in significantly lower mean viremia starting from week 21. Viral cccDNA was undetectable by conventional methods in the livers of 25% and 57% of animals co-immunized with DuIL-2 and DuIFN-γ, respectively. Interestingly, inoculation of liver homogenates from 7 such apparently resolved animals, exhibiting cccDNA undetectable in Southern blotting and DHBV expression undetectable or restricted to few hepatocytes, revealed that three liver homogenates transmitted high-titre viremia (3-5×10(10) vge/mL) to naïve animals. In conclusion, our results indicate that IFN-γ gene co-delivery considerably enhances immunotherapeutic efficacy of DNA vaccine targeting hepadnaviral proteins. Importantly, we also showed that livers exhibiting only minute amounts of hepadnaviral cccDNA could induce extremely high-titre infection, highlighting the caution that should be taken in occult hepatitis B patients to prevent HBV transmission in liver transplantation context.


J Viral Hepat


Saade F,Buronfosse T,Guerret S,Pradat P,Chevallier M,Zoulim F,Jamard C,Cova L




Has Abstract


2013-04-01 00:00:00












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    journal_title:Journal of viral hepatitis

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    更新日期:2002-03-01 00:00:00

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    更新日期:2001-01-01 00:00:00

  • Interferon alpha in the treatment of chronic hepatitis C in children: a meta-analysis [correction of metanalysis].

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    authors: Di Ciommo V,Russo P,Ravà L,Caprino L

    更新日期:2003-05-01 00:00:00

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    journal_title:Journal of viral hepatitis

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    authors: Kwak MS,Choi JW,Lee JS,Kim KA,Suh JH,Cho YS,Won SY,Park BK,Lee CK

    更新日期:2011-10-01 00:00:00

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    journal_title:Journal of viral hepatitis

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    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章


    authors: Moreno A,Bárcena R,García-Garzón S,Moreno L,Quereda C,Muriel A,Zamora J,Mateos ML,Pérez-Elías MJ,Antela A,Diz S,Moreno A,Moreno S

    更新日期:2006-07-01 00:00:00

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    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章


    authors: O'Gorman P,Strahan O,Ferguson D,Monaghan A,Kennedy M,Forde C,Melo AM,Doherty DG,O'Brien KK,McKiernan S,Kenny RA,Coen R,Doherty C,Bergin C,Gormley J,Norris S

    更新日期:2020-12-28 00:00:00

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    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章,评审


    authors: Puoti C,Guarisco R,Spilabotti L,Bellis L,Mitidieri Costanza O,Dell' Unto O,Elmo MG

    更新日期:2012-04-01 00:00:00

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    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章


    authors: Zhang ZH,Li L,Zhao XP,Glebe D,Bremer CM,Zhang ZM,Tian YJ,Wang BJ,Yang Y,Gerlich W,Roggendorf M,Li X,Lu M,Yang DL

    更新日期:2011-06-01 00:00:00

  • The large form of ADAR 1 is responsible for enhanced hepatitis delta virus RNA editing in interferon-alpha-stimulated host cells.

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    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章


    authors: Hartwig D,Schütte C,Warnecke J,Dorn I,Hennig H,Kirchner H,Schlenke P

    更新日期:2006-03-01 00:00:00

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    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章


    authors: Shudo E,Ribeiro RM,Perelson AS

    更新日期:2008-05-01 00:00:00

  • Quantification of hepatitis C virus in patients treated with peginterferon-alfa 2a plus ribavirin treatment by COBAS TaqMan HCV test.

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    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章


    authors: Kanda T,Imazeki F,Yonemitsu Y,Mikami S,Takada N,Nishino T,Takashi M,Tsubota A,Kato K,Sugiura N,Tawada A,Wu S,Tanaka T,Nakamoto S,Mikata R,Tada M,Chiba T,Kurihara T,Arai M,Fujiwara K,Kanai F,Yokosuka O

    更新日期:2011-07-01 00:00:00

  • Telbivudine treatment is associated with high hepatitis B e antigen seroconversion and immune modulatory effects in chronic hepatitis B patients.

    abstract::Chronic hepatitis B (CHB) is characterized by an impaired immune response to hepatitis B virus. Among the nucleos(t)ides used in CHB treatment, telbivudine is associated with the highest rates of hepatitis B e antigen (HBeAg) seroconversion rates, which are similar to those observed with pegylated interferon (PegIFN)....

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章,评审


    authors: Wang GQ,Ding YP,Dong YH

    更新日期:2013-04-01 00:00:00

  • Determination of hepatitis B phenotype using biochemical and serological markers.

    abstract::The aim of this study was to assess the validity of categorization of chronic hepatitis B viral infection into stages or phases based upon measures of disease activity and viral load, assuming these phenotypes will be useful for prognostication and determining the need for antiviral therapy. We assessed the phenotype ...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章


    authors: Di Bisceglie AM,Lombardero M,Teckman J,Roberts L,Janssen HL,Belle SH,Hoofnagle JH,Hepatitis B Research Network (HBRN).

    更新日期:2017-04-01 00:00:00

  • Long-term outcomes of direct acting antivirals in post-transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis.

    abstract::Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatiti...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章


    authors: Vukotic R,Conti F,Fagiuoli S,Morelli MC,Pasulo L,Colpani M,Foschi FG,Berardi S,Pianta P,Mangano M,Donato MF,Malinverno F,Monico S,Tamè M,Mazzella G,Belli LS,Viganò R,Carrai P,Burra P,Russo FP,Lenci I,Toniutto P

    更新日期:2017-10-01 00:00:00