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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.

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.

Eight donors immune to hepatitis B(HB)after natural infection were studied for their cellmediated immune response to hepatitis B core (HBc) protein in vitro. Significant specific activation was observed in highly purified peripheral blood lymphocytes and T cells from these donors after 5-8 days of incubation with HBc protein. This in vitro response wits modulated by monocytic cells and maximal ³H-thymidine incorporation was elicited with low concentrations of the antigen (0.1-10 ng/ml). The cell-mediated immune reactivity towards HBc-protein was significantly (P<0.005) elevated compared to the envelope material of the virus (HBsAg) when analysed in the same donor population. In contrast, donors with plasma-derived hepatitis B vaccine induced immunity lo HB exhibited only specific lymphocyte activation to HBsAg, These data Indicate that the composition of immune responses conferring protection against HBV after natural infection is far more complex than after immunization with the hepatitis B vaccine. Further characterization of the cell-mediated immune response to HBc protein and its relation to protection against HBV seems warranted when strategies for new HB-vaccines are being designed. [ABSTRACT FROM AUTHOR]