scholarly journals Potent human broadly neutralizing antibodies to hepatitis B virus from natural controllers

2020 ◽  
Vol 217 (10) ◽  
Author(s):  
Verena Hehle ◽  
Maxime Beretta ◽  
Maryline Bourgine ◽  
Malika Ait-Goughoulte ◽  
Cyril Planchais ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
B Cells ◽  
Hepatitis B ◽  
Neutralizing Antibodies ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Memory B Cells ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Rare individuals can naturally clear chronic hepatitis B virus (HBV) infection and acquire protection from reinfection as conferred by vaccination. To examine the protective humoral response against HBV, we cloned and characterized human antibodies specific to the viral surface glycoproteins (HBsAg) from memory B cells of HBV vaccinees and controllers. We found that human HBV antibodies are encoded by a diverse set of immunoglobulin genes and recognize various conformational HBsAg epitopes. Strikingly, HBsAg-specific memory B cells from natural controllers mainly produced neutralizing antibodies able to cross-react with several viral genotypes. Furthermore, monotherapy with the potent broadly neutralizing antibody Bc1.187 suppressed viremia in vivo in HBV mouse models and led to post-therapy control of the infection in a fraction of animals. Thus, human neutralizing HBsAg antibodies appear to play a key role in the spontaneous control of HBV and represent promising immunotherapeutic tools for achieving HBV functional cure in chronically infected humans.

scholarly journals Interaction between ganciclovir and foscarnet as inhibitors of duck hepatitis B virus replication in vitro.

1996 ◽  
Vol 40 (5) ◽  
pp. 1180-1185 ◽  
Author(s):  
G Civitico ◽  
T Shaw ◽  
S Locarnini
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Dna ◽  
Duck Hepatitis ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Dose Limiting Toxicity

Safe and effective treatments for chronic hepatitis B virus (HBV) infection have yet to be developed. Both ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanine) and foscarnet (trisodium phosphonoformate hexahydrate) are potent inhibitors of hepadnavirus replication when used individually in vitro and in vivo. However, the clinical usefulness of each drug is reduced by dose-limiting toxicity, especially during long-term monotherapy. Here we demonstrate additive inhibition of duck HBV DNA replication in cultures of primary duck hepatocytes congenitally infected with duck HBV by combinations of ganciclovir and foscarnet at low, clinically achievable concentrations. These results suggest that the effects of ganciclovir and foscarnet against HBV may be additive in vivo.

scholarly journals Evaluation of Single and Combination Therapies with Tenofovir Disoproxil Fumarate and EmtricitabineIn Vitroand in a Robust Mouse Model Supporting High Levels of Hepatitis B Virus Replication

2012 ◽  
Vol 56 (12) ◽  
pp. 6186-6191 ◽  
Author(s):  
Raymond F. Schinazi ◽  
Leda Bassit ◽  
Marcia M. Clayton ◽  
Bill Sun ◽  
James J. Kohler ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Combination Therapy ◽  
Virus Replication ◽  
Tenofovir Disoproxil Fumarate ◽  
Hbv Infection ◽  
Experimental Drugs ◽  
Chronic Hepatitis B Virus ◽  
B Virus

ABSTRACTNext-generation therapies for chronic hepatitis B virus (HBV) infection will involve combinations of established and/or experimental drugs. The current study investigated thein vitroandin vivoefficacy of tenofovir disoproxil fumarate (TDF) and/or emtricitabine [(−)-FTC] alone and in combination therapy for HBV infection utilizing the HepAD38 system (human hepatoblastoma cells transfected with HBV). Cellular pharmacology studies demonstrated increased levels of (−)-FTC triphosphate with coincubation of increasing concentrations of TDF, while (−)-FTC had no effect on intracellular tenofovir (TFV) diphosphate levels. Quantification of extracellular HBV by real-time PCR from hepatocytes demonstrated the anti-HBV activity with TDF, (−)-FTC, and their combination. Combination of (−)-FTC with TDF or TFV (ratio, 1:1) had a weighted average combination index of 0.7 for both combination sets, indicating synergistic antiviral effects. No cytotoxic effects were observed with any regimens. Using anin vivomurine model which develops robust HBV viremia in nude mice subcutaneously injected with HepAD38 cells, TDF (33 to 300 mg/kg of body weight/day) suppressed virus replication for up to 10 days posttreatment. At 300 mg/kg/day, (−)-FTC strongly suppressed virus titers to up to 14 days posttreatment. Combination therapy (33 mg/kg/day each drug) sustained suppression of virus titer/ml serum (<1 log10unit from pretreatment levels) at 14 days posttreatment, while single-drug treatments yielded virus titers 1.5 to 2 log units above the initial virus titers. There was no difference in mean alanine aminotransferase values or mean wet tumor weights for any of the groups, suggesting a lack of drug toxicity. TDF–(−)-FTC combination therapy provides more effective HBV suppression than therapy with each drug alone.

In vivo immunization in combination with peg-interferon for chronic hepatitis B virus infection

2007 ◽  
Vol 0 (0) ◽  
pp. 070214174036005-???
Author(s):  
D. Sprengers ◽  
R. G. van der Molen ◽  
R. Binda ◽  
J. G. Kusters ◽  
R. A. de Man ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Virus Infection ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Hepatitis B Virus Infection ◽  
Chronic Hepatitis B Virus ◽  
B Virus

scholarly journals Impaired generation of hepatitis B virus-specific memory B cells in HIV infected individuals following vaccination

Vaccine ◽  
2010 ◽  
Vol 28 (21) ◽  
pp. 3672-3678 ◽  
Author(s):  
Nishaki Mehta ◽  
Coleen K. Cunningham ◽  
Patricia Flynn ◽  
Joyce Pepe ◽  
Stephen Obaro ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
B Cells ◽  
Hepatitis B ◽  
Memory B Cells ◽  
Specific Memory ◽  
B Virus

scholarly journals Clinical Feature of Intrahepatic B-Lymphocytes in Chronic Hepatitis B

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Ashraf Mohamadkhani ◽  
Elnaz Naderi ◽  
Masoud Sotoudeh ◽  
Aezam Katoonizadeh ◽  
Ghodratollah Montazeri ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
B Cells ◽  
Hepatitis B ◽  
Liver Biopsy ◽  
B Lymphocytes ◽  
Chronic Hepatitis B ◽  
Hepatic Injury ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Humoral immunity constitutes major defense mechanism against viral infections. However, the association of hepatic injury and B-cells population in chronic hepatitis B virus (HBV) carriers has not been studied well. In this study, fifty seven hepatitis B surface antigen (HBsAg) positive and HBeAg negative patients were studied to determine the expression of CD20, a cell surface marker expressed on B-cells, in liver biopsy sections using immunohistochemistry. The patients’ clinical data at the time of liver biopsy were acquired from their medical records. There was a significant association between log HBV DNA and both ALT (r=0.36,P=0.006) and histologic activity index (HAI) total score (r=0.3,P=0.02), respectively. The CD20 was expressed in all 57 liver biopsy samples with a submembranous and membranous staining pattern and its expression was significantly associated with HAI total score (r=0.32,P=0.01) and stage of fibrosis (r=0.31,P=0.02). The susceptible B lymphocytes to hepatitis B virus might be implicated in the development of immune mediated inflammation of HBV-induced hepatic injury. The present data also support that the liver is potentially one of the secondary lymphoid organs.

scholarly journals Public broadly neutralizing antibodies against hepatitis B virus in individuals with elite serologic activity

2020 ◽  
Author(s):  
Qiao Wang ◽  
Eleftherios Michailidis ◽  
Yingpu Yu ◽  
Zijun Wang ◽  
Arlene M. Hurley ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Hbv Infection ◽  
Resistance Mutations ◽  
Broadly Neutralizing Antibodies ◽  
Peptide Epitope ◽  
Chronic Hepatitis B Virus ◽  
B Virus

SUMMARYAlthough there is no effective cure for chronic hepatitis B virus (HBV) infection, antibodies are protective and constitute clinical correlates of recovery from infection. To examine the human neutralizing antibody response to HBV in elite neutralizers we screened 144 individuals. The top individuals produced shared clones of broadly neutralizing antibodies (bNAbs) that targeted 3 non-overlapping epitopes on the HBV S antigen (HBsAg). Single bNAbs protected humanized mice against infection, but selected for resistance mutations in mice with established infection. In contrast, infection was controlled by a combination of bNAbs targeting non-overlapping epitopes with complementary sensitivity to mutations that commonly emerge during human infection. The co-crystal structure of one of the bNAbs with a peptide epitope containing residues frequently mutated in human immune escape variants revealed a loop anchored by oppositely charged residues. The structure provides a molecular explanation for why immunotherapy for HBV infection may require combinations of complementary bNAbs.

scholarly journals Hepatitis B Virus Pre-S Mutants as Biomarkers and Targets for the Development and Recurrence of Hepatocellular Carcinoma

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 945 ◽  
Author(s):  
Chiao-Fang Teng ◽  
Han-Chieh Wu ◽  
Ih-Jen Su ◽  
Long-Bin Jeng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Signal Pathways ◽  
Recurrence Rates ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC), the leading cause of cancer-related death worldwide. Despite progress in the prevention and therapy of HCC, high incidence and recurrence rates of HCC remain big threats, resulting in poor patient survival. Effective biomarkers and targets of HCC are therefore urgently needed for better management and to improve patient outcomes. Pre-S mutants have been well demonstrated as HBV oncoproteins that play important roles in HCC development through activation of multiple oncogenic signal pathways in hepatocytes, in vitro and in vivo. The presence of pre-S mutants in patients with chronic HBV infection and HBV-related HCC has been associated with a significantly higher risk of HCC development and recurrence after curative surgical resection, respectively. In this review, we summarize the roles of pre-S mutants as biomarkers for predicting HBV-related HCC development and recurrence, and highlight the pre-S mutants-activated oncogenic signal pathways as potential targets for preventing HBV-related HCC development.

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