Although DNA vaccination is now a promising strategy against hepatitis B virus (HBV) infection, this approach has relatively modest antiviral effect, indicating that immunosuppressive mechanisms may occur in the long-term established infection. In this study, we studied the immunogenicity and anti-HBV efficiency of a combination of HBV surface (HBsAg) and core (HBcAg) DNA vaccine, enhanced by heat shock protein (HSP) gp96 or HSP70 and mediated by in vivo electroporation. Immunization with gp96 adjuvanted HBsAg/HBcAg DNA formulation induced potent T cell and antibody immunity against HBsAg and HBcAg. Notably, treatment with gp96 or HSP70 as adjuvant resulted in reduction of Treg populations by around 20%. Moreover, compared with nonimmunized control mice, immunization with gp96 or HSP70 adjuvanted DNA vaccine dramatically decreased serum HBsAg and viral DNA levels, and HBcAg expression in liver. These results may therefore provide an effective strategy for designing gp96-based DNA vaccine for immunotherapy of chronic HBV infection.
Adjuvants, Immunologic ; Animals ; Electroporation ; HSP70 Heat-Shock Proteins ; immunology ; Hepatitis B Core Antigens ; immunology ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B Vaccines ; immunology ; Hepatitis B, Chronic ; prevention & control ; Immunization ; Membrane Glycoproteins ; immunology ; Mice ; Mice, Transgenic ; Vaccines, DNA ; immunology

Chronic hepatitis B (CHB) affects 350 million individuals worldwide. Perinatal transmission leads to high rates of chronic infection and complications, including cirrhosis and hepatocellular carcinoma. It is important to recognize and appropriately treat CHB in pregnancy, thereby reducing the risk of neonatal transmission and HBV-associated morbidity and mortality. Screening for CHB is recommended in all pregnant mothers as is universal vaccination of infants with hepatitis B virus (HBV) vaccine with or without hepatitis B immunoglobulin (HBIG). This has resulted in a lower incidence of HBsAg seropositivity and HCC in regions where universal infant vaccination has been endorsed. Mode of delivery and breastfeeding do not appear to affect HBV transmission rates based on available data. Overall, CHB does not increase perinatal maternal-fetal mortality. Administration of oral antiviral therapy during the third trimester to HBsAg-positive mothers with HBV DNA> or =7 log IU/mL may be useful in preventing breakthrough infection. Treatment may be considered earlier in pregnancy for persistently active liver disease shown by high ALT, HBV DNA levels and/or significant hepatic fibrosis. Lamivudine, tenofovir and telbivudine are safe and effective and are the agents of choice in pregnancy. However, further clinical studies are necessary to elucidate the role of antiviral therapy in the pregnant HBV carrier.
Antiviral Agents/therapeutic use ; Female ; Hepatitis B Surface Antigens/blood ; Hepatitis B Vaccines/immunology/therapeutic use ; Hepatitis B, Chronic/prevention & control/*therapy ; Humans ; Immunoglobulins/therapeutic use ; Infectious Disease Transmission, Vertical/prevention & control ; Pregnancy ; Pregnancy Complications, Infectious/prevention & control/*therapy

The outcome of liver transplantation for end-stage liver disease secondary to hepatitis B is remarkably impacted by recurrent infection and subsequent allograft failure. Pre-operational viral replication, immunosuppression degree, and disease types play an important role in hepatitis B recurrence. This article summarizes the mechanisms, the influencing factors, and clinical diagnosis for recurrence of hepatitis B following liver transplantation, and discusses multiple strategies to prevent hepatitis B recurrence. Lamivudine in combination with low-dose hepatitis B immuno-globulin currently is the most effective therapy to prevent recurrent hepatitis B virus allograft infection. It is emphasized that effective prophylaxis approaches against hepatitis B virus recurrence should be adopted before, during, and after operation. Long-term and even life-long antiviral therapy is important for a better outcome.
Combined Modality Therapy ; Hepatitis B Antibodies ; therapeutic use ; Hepatitis B virus ; immunology ; Hepatitis B, Chronic ; prevention & control ; Humans ; Immunoglobulins ; therapeutic use ; Lamivudine ; therapeutic use ; Liver Transplantation ; Postoperative Complications ; prevention & control ; Secondary Prevention

Pulse-induced permeabilization of cellular membranes, generally referred to as electroporation (EP), has been used for years as a tool to increase macromolecule uptake in tissues, including nucleic acids, for gene therapeutic applications, and this technique has been shown to result in improved immunogenicity. In this study, we assessed the utility of EP as a tool to improve the efficacy of HB-110, a novel therapeutic DNA vaccine against chronic hepatitis B, now in phase 1 of clinical study in South Korea. The potency of HB-110 in mice was shown to be improved by EP. The rapid onset of antigen expression and higher magnitude of humoral and cellular responses in electric pulse-treated mice revealed that EP may enable a substantial reduction in the dosage of DNA vaccine required to elicit a response similar in magnitude to that achievable via conventional administration. This study also showed that EP-based vaccination at 4-week-intervals elicited a cellular immune response which was about two-fold higher than the response elicited by conventional vaccination at 2-week intervals. These results may provide a rationale to reduce the clinical dose and increase the interval between the doses in the multidose vaccination schedule. Electric pulsing also elicited a more balanced immune response against four antigens expressed by HB-110: S, preS, Core, and Pol.
Animals ; Electroporation ; Hepatitis B Antigens/biosynthesis ; Hepatitis B Vaccines/administration & dosage/*immunology ; Hepatitis B, Chronic/*immunology/prevention & control ; Immunity, Cellular ; Male ; Mice ; Mice, Inbred BALB C ; Vaccines, DNA/administration & dosage/*immunology

BACKGROUND/AIMS: Few studies have investigated hepatitis A virus (HAV) seroepidemiology in Koreans with chronic liver disease (CLD). This study compared the prevalence of IgG anti-HAV between the general healthy population and patients with hepatitis B virus-related CLD (HBV-CLD), with the aim of identifying predictors of HAV prior exposure. METHODS: In total, 1,319 patients were recruited between June 2008 and April 2010. All patients were tested for IgG anti-HAV, hepatitis B surface antigen (HBsAg), and antibodies to hepatitis C virus. The patients were divided into the general healthy population group and the HBV-CLD group based on the presence of HBsAg. The seroprevalence of IgG anti-HAV was compared between these two groups. RESULTS: The age-standardized seroprevalence rates of IgG anti-HAV in the general healthy population and patients with HBV-CLD were 52.5% and 49.1%, respectively. The age-stratified IgG anti-HAV seroprevalence rates for ages < or =19, 20-29, 30-39, 40-49, 50-59, and > or =60 years were 14.3%, 11.2%, 45.5%, 90.5%, 97.6% and 98.3%, respectively, in the general healthy population, and 0%, 9.8%, 46.3%, 91.1%, 97.7%, and 100% in the HBV-CLD group. In multivariate analysis, age (<30 vs. 30-59 years: OR=19.339, 95% CI=12.504-29.911, P<0.001; <30 vs. > or =60 years: OR=1060.5, 95% CI=142.233-7907.964, P<0.001) and advanced status of HBV-CLD (OR=19.180, 95% CI=4.550-80.856, P<0.001) were independent predictors of HAV prior exposure. CONCLUSIONS: The seroprevalence of IgG anti-HAV did not differ significantly between the general-healthy-population and HBV-CLD groups. An HAV vaccination strategy might be warranted in people younger than 35 years, especially in patients with HBV-CLD.
Adolescent ; Adult ; Age Factors ; Aged ; Female ; Hepatitis A/complications/*epidemiology/prevention & control ; Hepatitis A Antibodies/*blood ; Hepatitis A virus/immunology ; Hepatitis B Surface Antigens/blood ; Hepatitis B, Chronic/*complications ; Humans ; Immunoglobulin G/*blood ; Male ; Middle Aged ; Republic of Korea ; Seroepidemiologic Studies ; Sex Factors ; Vaccination

Adult ; Carrier State ; drug therapy ; Female ; Hepatitis B, Chronic ; complications ; drug therapy ; immunology ; Humans ; Immunologic Deficiency Syndromes ; complications ; Lamivudine ; therapeutic use ; Male ; Middle Aged ; Secondary Prevention

<b>OBJECTIVEb>To observe the effect of Chinese medicine therapy for strengthening-Pi and nourishing-Shen (SPNS) in preventing lamivudine induced YMDD mutation and its immunological mechanism.

<b>METHODSb>One hundred and sixty chronic hepatitis B (CHB) patients with positive HBeAg were equally assigned to two groups at random: the observation group and the control group. Patients in the observation group were treated with lamivudine combined with SPNS, and those in the control group were treated with lamivudine only, with the treatment lasting for 52 weeks in total. Changes in indexes, including liver function, HbeAg, HBV-DNA, YMDD variation, CD(4), CD(4)/CD(8) ratio, interferon-gamma (IFN-gamma), interleukin-4 (IL-4), blood routine, renal function, as well as any adverse reactions that occurred in patients, were observed at different time points.

<b>RESULTSb>The ALT, AST recovery rate and HBV-DNA negatively inversing rate at the 24th week, the 36th week and the 52nd week were all higher (P<0.05); meanwhile, the YMDD mutation rate at the 36th week and the 52nd week was lower (P<0.05) in the observation group than in the control group. The posttreatment levels of CD(4), CD(4)/CD(8) ratio, IFN-gamma, and IL-4 as well as the pre-post treatment difference of these indexes in the observation group were significantly different from those in the control group (P<0.05).

<b>CONCLUSIONb>Chinese medicine SPNS therapy can significantly reduce the YMDD variation of HBV, and the mechanism may be related to its regulation of the CD(4) level, CD(4)/CD(8) ratio and Th1/Th2 balance.

Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; DNA, Viral ; genetics ; Drug Resistance, Viral ; drug effects ; genetics ; immunology ; Female ; Genes, Viral ; Hepatitis B virus ; genetics ; immunology ; Hepatitis B, Chronic ; drug therapy ; immunology ; prevention & control ; virology ; Humans ; Immune Evasion ; genetics ; Lamivudine ; adverse effects ; therapeutic use ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Mutation ; physiology ; Palliative Care ; methods ; Secondary Prevention ; Young Adult