Induction of anti-HBs in HB vaccine nonresponders in vivo by hepatitis B surface antigen-pulsed blood dendritic cells.

BACKGROUND/AIMS: Antigen-pulsed dendritic cells (DCs) are now used for treatment of patients with cancers, however, the efficacy of these DCs has never been evaluated for prophylactic purposes. The aim of this study was (1) to prepare hepatitis B surface antigen (HBsAg)-pulsed human blood DCs, (2) to assess immunogenicity of HBsAg-pulsed DCs in vitro and (3) to evaluate the efficacy of HBsAg-pulsed DCs in hepatitis B (HB) vaccine nonresponders. METHODS: Human peripheral blood DCs were cultured with HBsAg to prepare HBsAg-pulsed DCs. The expression of immunogenic epitopes of HBsAg on HBsAg-pulsed DCs was assessed in vitro. Finally, HBsAg-pulsed DCs were administered, intradermally to six HB vaccine nonresponders and the levels of antibody to HBsAg (anti-HBs) in the sera were assessed. RESULTS: HB vaccine nonresponders did not exhibit features of immediate, early or delayed adverse reactions due to administration of HBsAg-pulsed DCs. Anti-HBs were detected in the sera of all HB vaccine nonresponders within 28 days after administration of HBsAg-pulsed DCs. CONCLUSIONS: This study opens a new field of application of antigen-pulsed DCs for prophylactic purposes when adequate levels of protective antibody cannot be induced by traditional vaccination approaches.

In vivo immunization by vaccine therapy following virus suppression by lamivudine: a novel approach for treating patients with chronic hepatitis B.

BACKGROUND: Both the hepatitis B virus (HBV) and the immune response of the hosts to HBV play important roles in the pathogenesis of chronic hepatitis B (CHB). Lamivudine is a potent antiviral agent with minimal immune modulator capacity. Moreover, lamivudine causes severe side effects like breakthrough of HBV DNA and breakthrough hepatitis in patients with CHB. On the other hand, vaccine therapy, a recently-developed immune therapy, exhibits potent immune modulatory potentials and almost no side effects, but possesses little antiviral capacity in patients with CHB. OBJECTIVES: The aim of this clinical trial is to evaluate the efficacy of a combination therapy of lamivudine and vaccine in patients with CHB. STUDY DESIGN: Seventy-two patients with CHB (hepatitis B e antigen (HBeAg)-positive, 40; antibody to HBeAg (anti-HBe)-positive, 32). All patients received lamivudine at a dose of 100 mg daily for 12 months. Fifteen patients (HBeAg+, 9; anti-HBe+, 6) receiving oral lamivudine were also given a vaccine containing 20 microg of hepatitis B surface antigen, intradermally, once every 2 weeks for 12 times (combination therapy). RESULTS: Twelve months after the start of therapy, serum HBV DNA became negative in 9 of 9 (100%) HBeAg+ CHB patients receiving combination therapy and in 15 of 31 (48%) HBeAg+ CHB patients receiving lamivudine monotherapy (P < 0.05). The rate of seroconversion from HBeAg to anti-HBe was also significantly higher in patients receiving combination therapy (56% versus lamivudine monotherapy, 16%, P < 0.05). Of the 57 patients receiving lamivudine monotherapy, breakthrough of HBV DNA was found in 10 and breakthrough hepatitis was found in 4; however, these were not seen in any patient receiving combination therapy. CONCLUSIONS: Combination therapy represents a better therapeutic regimen with few complications in patients with CHB.

Safety and efficacy of hepatitis B surface antigen-pulsed dendritic cells in human volunteers.

Hepatitis B surface antigen (HBsAg)-pulsed murine spleen dendritic cells (DCs) have shown tremendous therapeutic potentials in chronic hepatitis B virus (HBV) carriers however, there has been no study regarding the feasibility of using HBsAg-pulsed DCs in human. Five human healthy volunteers with no apparent concomitant diseases were enrolled in this study. DCs were enriched from peripheral blood of each volunteer in endotoxin-free and sterilized conditions. HBsAg-pulsed DCs were prepared by culturing DCs with a commercial-available human grade vaccine containing HBsAg. After assessing the expression of HLA DR and CD86 on HBsAg-pulsed DCs, 5 million HBsAg-pulsed DCs were injected intradermally, once, to each volunteer. The volunteers were serially observed for safety and efficacy of administration of HBsAg-pulsed DCs. No evidence of physical, biochemical, and immunological abnormalities were documented in any volunteer during the next 28 days following administration of HBsAg-pulsed DCs. A single administration of HBsAg-pulsed DCs resulted in upregulation of anti-HBs in two anti-HBs(+) volunteers. Moreover, anti-HBs were detected in two anti-HBs(-) volunteer, 2 weeks after administration of HBsAg-pulsed DCs. This study provides the scientific and ethical basis for using HBsAg-pulsed DCs for therapeutic and prophylactic purposes in patients with chronic hepatitis B and non-responders to hepatitis B vaccine, respectively.

Mechanism of action of low recurrence of gastritis caused by Helicobacter pylori with the type II urease B gene.

BACKGROUND: Low recurrence of gastritis is seen in patients infected with Helicobacter pylori carrying the type II urease B gene, compared with H. pylori carrying types I and III. The underlying mechanism has been studied in terms of the urease activity and interleukin (IL)-8 production capacity of different strains of H. pylori. MATERIALS AND METHODS: Forty-five patients infected with different strains of H. pylori (type I; 15, type II; 15 and type III; 15) were enrolled in the study. H. pylori was isolated from gastric mucosa and cultured in the presence of urea at pH 5.5 to evaluate urease activity. The capacity of different strains of H. pylori to induce IL-8 mRNA and IL-8 from a human gastric cancer cell line and human peripheral blood mononuclear cells was evaluated. RESULTS: The urease activity of type II H. pylori[523 +/- 228 micro g of ammonia/dl/10(8) colony-forming units (CFU)/ml] was significantly lower than that of type I (1355 +/- 1369 micro g of ammonia/dl/10(8) CFU/ml) and type III (1442 +/- 2229 micro g of ammonia/dl/10(8) CFU/ml) (p <.05). Gastric cancer cells cocultured with type II H. pylori produced lower levels of IL-8 mRNA compared with type I and type III H. pylori. The levels of IL-8 were also significantly lower in cultures induced by type II H. pylori compared with those induced by type I and type III H. pylori. Peripheral blood mononuclear cells also produced lower levels of IL-8 when cocultured with type II compared with type I H. pylori. CONCLUSIONS: These results indicate that both the lower level of urease activity and the low IL-8-inducing capacity of type II H. pylori might underlie the lower recurrence rate of gastritis caused by type II H. pylori.