Immune therapy of hepatitis B virus chronic infection

Pol, Stanislas; Michel, Marie‐Louise; Bréchot, Christian

doi:10.1002/hep.510310249

Cited by 6 publications

(4 citation statements)

References 8 publications

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“…Nucleoside analogues such as lamivudine have exhibited highly effective antiviral activity, but mutations in the viral genome are frequently associated with a recurrence of HBV replication (Fontaine et al , 1999 ; Zoulim & Trepo, 1999 ). In this context, a new approach to HBV treatment has been proposed, consisting of immunotherapy using vaccination with recombinant envelope proteins (Pol et al , 1994 , 2000 ). Clinical trials have suggested a reduction of at least 50% or clearance of HBV replication in about 30% of chronic HBV carriers 3 months after three monthly doses of S (Recombivax) or preS2/S (GenHevac B) vaccines (Pol et al , 1994 , 2000 ).…”

Section: Full Textmentioning

confidence: 99%

“…In this context, a new approach to HBV treatment has been proposed, consisting of immunotherapy using vaccination with recombinant envelope proteins (Pol et al , 1994 , 2000 ). Clinical trials have suggested a reduction of at least 50% or clearance of HBV replication in about 30% of chronic HBV carriers 3 months after three monthly doses of S (Recombivax) or preS2/S (GenHevac B) vaccines (Pol et al , 1994 , 2000 ). This is reinforced further by an induction of the CD4 + T cell response during this treatment (Couillin et al , 1999 ).…”

Section: Full Textmentioning

confidence: 99%

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Vaccination of chronic hepatitis B virus carriers with preS2/S envelope protein is not associated with the emergence of envelope escape mutants

Soussan

Pol

Garreau

et al. 2001

Journal of General Virology

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PreS2/S vaccination of chronic hepatitis B virus (HBV) carriers led to a reduction in HBV replication or clearance of virus in 30 % of treated patients. This study assessed whether vaccinotherapy of chronic HBV carriers induced the selection of escape mutants in the envelope ' a ' determinant and whether envelope genetic variability might affect the response to vaccination. No amino acid differences were observed in the ' a ' determinant between sequences obtained before and after treatment (five responders and seven nonresponders). However, alignment with HBV prototype sequences revealed seven amino acid changes. Two mutations (T140S and P127L) diverged from subtype variations. In the complete envelope sequence (five non-responders and five responders), ten amino acid modifications were detected between sequences obtained before and after treatment. The absence of any common mutations did not enable the definition of a hot spot of mutations implicated in the response to vaccination. Moreover, vaccinotherapy does not induce the selection of escape mutants in the ' a ' determinant.

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Section: Full Textmentioning

confidence: 99%

Section: Full Textmentioning

confidence: 99%

Vaccination of chronic hepatitis B virus carriers with preS2/S envelope protein is not associated with the emergence of envelope escape mutants

Soussan

Pol

Garreau

et al. 2001

Journal of General Virology

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“…Chronic HBV patients are either vaccinated with peptides that stimulate CTL activity (Alexander et al 1998;Livingston et al 1999) or simply vaccinated with standard HBs-containing vaccines with 6 injections of the standard dose of vaccine over i year (Couillin et al 1999;Pol et al 2000). Neither schedule for therapeutic vaccination led to a breakthrough in HBV therapy.…”

Section: Therapeutic Vaccinationmentioning

confidence: 99%

Recombinant hepatitis B Vaccines – Disease Characterization and Vaccine Production

Brocke¹,

Schaefer

Melber³

et al. 2002

Hansenula Polymorpha

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“…Specific immunotherapeutic strategies have been proposed as possible alternatives to the use of IFN or antiviral drugs to enhance or to broaden the defective T-cell responses in chronically infected patients. Among these, specific vaccine therapies with either currently available recombinant anti-hepatitis B vaccines (9,40), a lipopeptide-based T-cell vaccine (53), or newly developed genetic vaccines (31,33,42) have been studied recently with animal models or in human clinical trials (19,40).…”

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CpG Oligodeoxynucleotides with Hepatitis B Surface Antigen (HBsAg) for Vaccination in HBsAg-Transgenic Mice

Malanchère-Brès

Payette

Mancini

et al. 2001

J Virol

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DNA motifs containing unmethylated CpG dinucleotides within the context of certain flanking sequences enhance both innate and antigen-specific immune responses, due in part to the enhanced production of Th1-type cytokines. Here we explored the ability of CpG-containing oligodeoxynucleotides combined with recombinant hepatitis B surface antigen (HBsAg) to induce Th1 responses in mice that are transgenic for this antigen and that represent a model for asymptomatic hepatitis B virus chronic carriers. This was compared to hepatitis B virus-specific DNA-mediated immunization, which we have previously shown to induce the clearance of the transgene expression product and the down-regulation of hepatitis B virus mRNA in this transgenic mouse lineage. In control nontransgenic C57BL/6 mice, three immunizations with HBsAg and CpG triggered the production of anti-HBs antibodies and of HBs-specific T cells that secrete gamma interferon but do not display any HBsAg-specific cytotoxic activity. In the HBsAg-transgenic mice, immunization with HBsAg and CpG oligodeoxynucleotides, but not with CpG alone, induced the clearance of HBsAg circulating in the sera, with a concomitant appearance of specific antibodies, and was able to regulate the hepatitis B virus mRNA constitutively expressed in the liver. Finally, adoptive transfer experiments with CD8 ؉ T cells primed in C57BL/6 mice with HBsAg and CpG oligodeoxynucleotide-based immunization show that these cells were able to partially control transgene expression in the liver and to clear the HBsAg from the sera of recipient transgenic mice without an antibody requirement. CpG oligodeoxynucleotides motifs combined with HBsAg could therefore represent a potential therapeutic approach with which to treat chronically infected patients.

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Immune therapy of hepatitis B virus chronic infection

Cited by 6 publications

References 8 publications

Vaccination of chronic hepatitis B virus carriers with preS2/S envelope protein is not associated with the emergence of envelope escape mutants

Vaccination of chronic hepatitis B virus carriers with preS2/S envelope protein is not associated with the emergence of envelope escape mutants

Recombinant hepatitis B Vaccines – Disease Characterization and Vaccine Production

CpG Oligodeoxynucleotides with Hepatitis B Surface Antigen (HBsAg) for Vaccination in HBsAg-Transgenic Mice

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