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Combination of DNA Prime - Adenovirus Boost Immunization with Entecavir Elicits Sustained Control of Chronic Hepatitis B in the Woodchuck Model
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نویسنده
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kosinska a.d. ,zhang e. ,johrden l. ,liu j. ,seiz p.l. ,zhang x. ,ma z. ,kemper t. ,fiedler m. ,glebe d. ,wildner o. ,dittmer u. ,lu m. ,roggendorf m.
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منبع
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plos pathogens - 2013 - دوره : 9 - شماره : 6
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چکیده
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A potent therapeutic t-cell vaccine may be an alternative treatment of chronic hepatitis b virus (hbv) infection. previously,we developed a dna prime-adenovirus (adv) boost vaccination protocol that could elicit strong and specific cd8+ t-cell responses to woodchuck hepatitis virus (whv) core antigen (whcag) in mice. in the present study,we first examined whether this new prime-boost immunization could induce whcag-specific t-cell responses and effectively control whv replication in the whv-transgenic mouse model. secondly,we evaluated the therapeutic effect of this new vaccination strategy in chronically whv-infected woodchucks in combination with a potent antiviral treatment. immunization of whv-transgenic mice by dna prime-adv boost regimen elicited potent and functional whcag-specific cd8+ t-cell response that consequently resulted in the reduction of the whv load below the detection limit in more than 70% of animals. the combination therapy of entecavir (etv) treatment and dna prime-adv boost immunization in chronic whv carriers resulted in whsag- and whcag-specific cd4+ and cd8+ t-cell responses,which were not detectable in etv-only treated controls. woodchucks receiving the combination therapy showed a prolonged suppression of whv replication and lower whsag levels compared to controls. moreover,two of four immunized carriers remained whv negative after the end of etv treatment and developed anti-whs antibodies. these results demonstrate that the combined antiviral and vaccination approach efficiently elicited sustained immunological control of chronic hepadnaviral infection in woodchucks and may be a new promising therapeutic strategy in patients. © 2013 kosinska et al.
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آدرس
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institute of virology,university hospital of essen,essen, Germany, institute of virology,university hospital of essen,essen,germany,wuhan institute of virology,chinese academy of sciences,wuhan, China, department of molecular and medical virology,institute of microbiology and hygiene,ruhr-university bochum,bochum, Germany, institute of virology,university hospital of essen,essen, Germany, institute of medical virology,national reference centre for hepatitis b and d viruses,justus-liebig university,giessen, Germany, institute of virology,university hospital of essen,essen,germany,hepatology unit and department of infectious diseases,nanfang hospital,southern medical university,guangzhou, China, institute of virology,university hospital of essen,essen, Germany, institute of virology,university hospital of essen,essen, Germany, institute of virology,university hospital of essen,essen, Germany, institute of medical virology,national reference centre for hepatitis b and d viruses,justus-liebig university,giessen, Germany, paul-ehrlich-institut,division of medical biotechnology,langen, Germany, institute of virology,university hospital of essen,essen, Germany, institute of virology,university hospital of essen,essen, Germany, institute of virology,university hospital of essen,essen, Germany
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Authors
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