Modulation of serum interleukin-18 concentrations and hepatitis B virus DNA levels during interferon therapy in patients with hepatitis B e-antigen-positive chronic hepatitis B.

The aim of this study was (1) to determine plasma values of interleukin-18 (IL-18) in patients with different clinical manifestations of hepatitis B (HB) and (2) to analyze the correlation between presence of circulatory levels of IL-18 and levels of HB virus (HBV) DNA during interferon-alpha (IFN-α)-induced HBe seroconversion in patients with chronic HB (CHB). The IL-18 levels in serum did not significantly differ between healthy control subjects (99 ± 25 pg/mL), HB-immune patients (85 ± 33), and asymptomatic carriers of HB surface antigen (144 ± 44 pg/mL). In contrast, anti-HBe (HBV DNA <104 copies/mL, 555 ± 248, P < 0.05), anti-HBe (HBV DNA >104 copies/mL, 280 ± 85, P < 0.05), and HBe-antigen-reactive (373 ± 108, P < 0.0001) patients with symptomatic CHB had significantly elevated levels in circulation compared with healthy control subjects (99 ± 25 pg/mL). An inverse correlation was found between serum HBV DNA copies and IL-18 levels during therapy (r = -0.54, P < 0.001). We consistently observed an IFN-α-induced suppression of viral replication, which was followed by the alanine aminotransferase (ALT) flare. There was a significant increase in IL-18 production after the ALT flare, where the peak of IL-18 preceded or coincided with the time of HBe seroconversion in patients who cleared the virus. These results suggest that IL-18 is involved in the pathogenesis of CHB and that IFN-α therapy can augment the production of IL-18 in patients with CHB.

Anti-preS responses influence the anti-HBs response in newborns after vaccination with the third generation Sci-B-Vac vaccine.

We analysed the specificity and significance of the antibody response towards the linear preS1 sequence that has been shown to represent the "hepatocyte binding site" comprising amino acids preS1 (21-47) or the specific preS2 (131-140) antibody response to the "polymerised albumin receptor" in relation to the antibody response to hepatitis B surface antigen during immunisation of healthy children with the preS-containing Sci-B-Vac vaccine. Twenty-eight healthy newborns received three doses of the Sci-B-Vac vaccine according to a 0-, 1-, and 6-month scheme. Seventeen (61%) of the 28 newborns had detectable levels of anti-preS1 (21-47) antibodies and 14 (50%) were anti-preS2 (131-140) reactive at 6 and/or 9 months after initiation of the vaccination. The mean levels of anti-HBs were significantly higher in the anti-preS2 (131-140) non-reactive (24580+/-7815IU/l, mean+SEM) compared with the reactive sera (7287+/-2317IU/l, p<0.025). The highest anti-HBs levels were found in newborns who exhibited reactivity towards the aa 21-47 of the preS1 but lacked anti-preS2 (131-140) reactivity.

PreS1 epitope recognition in newborns after vaccination with the third-generation Sci-B-Vac vaccine and their relation to the antibody response to hepatitis B surface antigen.

BACKGROUND: Sci-B-Vac is a recombinant, hepatitis B vaccine derived from a mammalian cell line and containing hepatitis B surface antigen (HBsAg) as well as preS1 and preS2 antigens. Few studies have been performed on the antibody responses to preS1 in relation to the antibody to hepatitis B surface antigen (anti-HBs) response during immunisation of healthy children with preS-containing vaccines. RESULTS: In this study 28 healthy newborns were randomly selected to receive either 2.5 microg or 5.0 microg of the Sci-B-Vac vaccine. Children received three doses of vaccine according to a 0-, 1-, 6-month scheme. Antibodies against the S-protein and three synthetic peptides mimicking three B-cell preS1 epitopes, (21-32 amino acid epitope), (32-47 amino acid epitope) and the C-terminal (amino acid epitope 94-117) were determined at 6 and 9 months. Fourteen (50%) of the 28 newborns had detectable levels of anti-preS1 (21-32) antibodies; 15 (54%) were anti-preS1 (32-47) reactive and 12 (43%) were anti-preS1 (94-117) reactive at 6 or 9 months after initiation of the vaccination. Significantly higher levels of anti-HBs were observed in the sera of patients with detectable anti-preS1 (32-47) reactivity (24 550 +/- 7375 IU/L, mean +/- SEM) as compared with the non-reactive sera (5991 +/- 1530 IU/L, p < 0.05). The anti-HBs levels were significantly lower if none (p < 0.05) or one (p < 0.025) of the preS1 (21-32, 32-47, 94-117) peptides were recognised compared with the anti-HBs levels if two or three peptides were recognised. CONCLUSION: Recognition of several preS1 epitopes, and in particular, the epitope contained within the second half of the hepatocyte binding site localised in the hepatitis B surface protein of the third-generation hepatitis B vaccine is accompanied by a more pronounced antibody response to the S-gene-derived protein in healthy newborns.