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Abstract 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 ug or 5.0 ug 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.

Blood lymphocytes from thirteen patients with CLL were studied for surface-bound Ig (SIg), Fc receptors (EA rosettes), receptors for sheep erythrocytes (E rosettes) and receptors for Helix pomatia A haemagglutinin (FTP), a carbohydrate-binding protein with specificity for N-acetyl-D- galactosamine and related sugars. Fluorescein-labelled HP binds to subpopulations of human peripheral blood lymphocytes (PBL) treated with neuraminidase. In normal peripheral blood, HP binds to the T-lymphocytes while the majority of the B cells bearing surface-bound immunoglobulin do not have receptors for HP. In untreated CLL, HP binds to 90-100% of the neur-aminidase-treated PBL. Almost all of the SIg-positive cells in CLL patients also have receptors for HP. Two groups of patients were found: in one the total fraction of SIg&plus; cells was &les;50% and about 30% of these lost their Ig during incubation at 37° C. No such loss of Slig was revealed in the remaining patients where total SIg&plus;fraction was &ap;70%. These patients usually had higher blood lymphocyte counts, probably reflecting a more advanced disease. CLL patients in remission with low numbers of leukaemic cells also had low numbers of blood lymphocytes carrying both SIg and HP-receptors. It is concluded that leukaemic cells carry both HP receptors and SIg. Testing of this combination therefore provides a valuable new tool for monitoring patients with CLL. [ABSTRACT FROM AUTHOR]

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]

Cell mediated and humoral immunity to hepatitis B surface antigen (HBsAg) was studied in nine asymptomatic HBsAg carriers, nine patients with natural acquired immunity to MB infection and nine HB-susceptible donors. Peripheral T and B lymphocytes from all asymptomatic HBsAg carriers and all HB-immune donors studied were specifically induced into proliferation and anti-HBs secretion when stimulated with low doses of HBsAg (2-30 ng antigen protein/ml) in vitro. This activation was achieved by mixing purified B and/or T cells with optimal concentrations of autologous monocytic cells. T and B cells from the HB-susceptible donors were non-responsive under identical culture conditions. These data do neither substantiate the existence of a qualitative defect in T cell function, nor the absence of circulatory B cells capable of synthesizing anti-HBs in vitro in asymptomatic HBsAg carriers. Thus, the inability to mount a satisfactory antibody response to HBsAg in vivo might be a consequence of altered immune responsiveness to this antigen, which may be a relevant factor in the pathogenesis of asymptomatic HBsAg carriership. [ABSTRACT FROM AUTHOR]

The article focuses on human serum albumin (HSA) and the enigma of chronic hepatitis type B. The interaction between HSA and virus particles permits the entrance of HBV into uninfected hepatocytes. It has been demonstrated that antigen associated with self carriers induces immunological unresponsiveness. The ease of tolerance induction is favoured by intravenous administration of antigen in high concentration in soluble form. Immature B cells in neonates are highly susceptible to tolerance induction. Reactive B-cell clones are deleted or rendered anergic when exposed to antigen in a tolerogenic form.

The occurrence of immunoglobulin determinants on the surface of lymphocytes from human blood was assessed by indirect immunofluorescent staining of living cells after cultivation with phytohaemaggtutinin or other stimulants. While antisera to γ, μ or α-determinants only stained a few cells, antisera to light chain determinants stained a larger proportion of the cells. Positive staining was recognized as 'ring' staining comprising smaller or larger parts of the cell surface. The specificity of staining was ascertained by several types of controls. After 48 hours of cultivation, anti-κ serum, applied at dilutions of 1:10-1:16 stained about 35-50 per cent and anti-λ serum about 15-20 per cent of the cells in the PHA cultures but only 3-5 per cent in the cultures incubated without PHA. When the antisera were applied at higher concentrations, positive light chain staining was also seen in the unstimulated cultures. At the highest concentrations, which could be used without increasing the non-specific background, the maximum number of κ-positive cells in the unstimulated cultures was approximately 25 per cent. Antiserum titrations showed that about 5-10 times less antiserum was needed to stain the optimal fraction of PHA treated cells. No increased staining of heavy chain determinants was achieved by increasing antiserum concentrations under the present conditions. Similar results were obtained with lymphocytes stimulated by 3 days of incubation with concanavalin A, or by 6-7 days of incubation under mixed culture conditions. Lymphocytes of a tuberculin positive donor also gave increased staining for light chain determinants after incubation for 6-7 days with antigen (PPD). The results indicate that lymphocyte stimulation is accompanied by increased amounts of surface bound immunoglobulins, At the present stage of knowledge, several explanations may account for the fact that light chain determinants are primarily accessible for staining. The above results were obtained under conditions in which no protein was present in the washings performed during processing for immunofluorescence. In the presence of low concentrations of protein more than 60 per cent of both unstimulated andstimulated cells stained for light chain determinants, while staining for heavy chain determinants remained unchanged and at a low level. It is possible that protein-free washing removed a more loosely adsorbed immunoglobulin fraction passed on from producing to neighbouring non-producing cells. [ABSTRACT FROM AUTHOR]