Immunogenicity of 20 μg of recombinant DNA hepatitis B vaccine in healthy neonates: A comparison of three different vaccination schemes

The immunogenicity of a full dose (20 μg) of recombinant DNA yeast-derived hepatitis B vaccine (Engerix-B) was assessed in healthy neonates in order to compare three candidate vaccination schemes. After randomization 162 newborns of hepatitis B surface antigen (HBsAg) negative mothers entered the study. Neonates received hepatitis B vaccine according to a fourdose vaccination scheme starting either at month 3 (scheme I: months 3,4,5, and 11) or at birth (scheme III: months 0,1,2, and 11). Another group of neonates received hepatitis B vaccine according to a three-dose scheme starting at birth (scheme II: months 0, 1, and 6). Serious adverse reactions were not observed; 2.5% of the vaccinated newborns suffered mild transient local symptoms. The vaccine was highly immunogenic irrespective of vaccination scheme; all infants developed anti-HBs levels ≥10 IU/L, 97% ≥100 IU/L. The immunogenicity of hepatitis B vaccine after primary and booster vaccinations, administered in the four-dose scheme started at birth, was significantly higher (P< 0.05) than in the three-dose scheme started at birth. Hepatitis B vaccination according to the four-dose scheme started at month 3 produced significantly higher (P < 0.05) antibody levels in comparison to the four-dose scheme started directly after birth. This study showed that a fourdose hepatitis B vaccination scheme starting at month 3 resulted in the highest antibody levels of the three schemes investigated and can be recommended for incorporation in the Expanded Programme on Immunization in The Netherlands.     

German experimental hepatitis B vaccine — Influence of variation of dosage schedule,sex and age differences on immunogenicity in health care workers

Summary Of the medical staff of our hospital 217 members at high risk for hepatitis B were immunized with an experimental hepatitis B vaccine and anti-HBs titers used to study the influence of two dosage schedules, age, and sex on immunogenicity. Participants were 34 years of age (mean; range, 20–61); they were divided into two groups and vaccinated three times. Group A received 42 µg HBsAg for each vaccination. Group B received 84 µg for the first and 21 µg for the second and third vaccinations. The seroconversion rate was 32.7% after the first, 78.8% after the second, and 95.7% after the third vaccination. The participants who failed to produce anti-HBs titer (3 IU/l;n=9) or whose anti-HBs titers were below 50 IU/l (n=31) were vaccinated a fourth time. Only mild side effects of injections were observed in a third of all participants, usually in the form of a sore arm.Between groups A and B there were no significant differences as far as the seroconversion rate and anti-HBs titer were concerned. Nonresponders plus low-responders accounted for 19%. Female participants produced a markedly higher anti-HBs titer than males, and the female/male ratio among non- and low-responders was 1:2; among nonresponders, 1:2.5. There was a negative correlation of the anti-HBs titer with the age of the participants. These results not only have practical consequences for revaccination policy, but also offer the opportunity to further study the genetic regulation of the immune response to a complex peptide antigen in man.Abbreviations anti-HBc antibody to hepatitis B core antigen - anti-HBe antibody to hepatitis B e antigen - anti-HBs antibody to hepatitis B surface antigen - HBsAg hepatitis B surface antigen - IU/l international units per liter - MSD Merck, Sharp, and Dohme     

The antibody response to HBs antigen is regulated by coordinated Th1 and Th2 cytokine production in healthy neonates

A proportion of healthy neonates fail to produce protective levels of anti-HBs antibody following vaccination with recombinant hepatitis B vaccine. This study was undertaken to investigate contribution of Th1 and Th2 responses to anti-HBs antibody production and to explore the mechanism(s) of unresponsiveness to HBsAg in human neonates. Peripheral blood manonuclear cells (PBMCs) were isolated form 28 nonresponder (anti-HBs antibody <10 IU/l) and 25 responder neonates. The cells were stimulated in vitro with recombinant HBsAg and PHA mitogen and concentrations of IL-4, IL-10 and IFN-gamma were quantified in culture supernatants by sandwich ELISA. Our results demonstrated significantly increased production of all cytokines, including IL-4 (P < 0.001), IL-10 (P < 0.002) and IFN-gamma (P < 0.01) in responder compared to nonresponder vaccinees. No significant differences, however, were observed between the two groups of neonates in the levels of cytokines induced by PHA or secreted in absence of antigen and mitogen. Our findings suggest that unresponsiveness to recombinant HBsAg in healthy neonates is linked to inadequate secretion of both Th1 and Th2 cytokines.     

The immune response of healthy Nigerian adults to small doses of hepatitis B vaccine: comparison of 10- and 20-micrograms doses

The immunogenic effect of hepatitis B vaccine (H-B-vax) was evaluated in 120 seronegative healthy Nigerians. Three doses of the vaccine were given at 0, 1, and 6 months. Serial blood samples were tested 1 month after each vaccination for hepatitis B surface antibody (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc). Of 60 vaccines given 20 micrograms of the vaccine, 40% had significant anti-HBs response 1 month after the first dose, 70% after the second dose, and 91.7% after the third dose. In the 60 vaccines given 10-micrograms doses, the seroconversion rates were 35, 73.3, and 90%, respectively. It is concluded that this vaccine in 10-micrograms doses is as effective as the larger doses in producing anti-HBs. The administration of small doses would reduce the cost of large-scale vaccination programs in developing countries.     

Safety and immunogenicity of a recombinant hepatitis B vaccine

A hepatitis B vaccine produced in yeast by recombinant DNA technology was evaluated using 5-micrograms and 10-micrograms doses in a randomized trial lasting 7 months in 110 male armed forces recruits aged 17-19 years. Results were compared to those of an identical trial of a plasma-derived vaccine. No allergic reactions were observed, and the rate of mild side effects was similar to the plasma-derived vaccine. Seroconversion rates in the first month were 60% (33/55) and 67% (37/55) with the 5-micrograms and 10-micrograms doses of the recombinant vaccine, respectively. All participants seroconverted by 3 months, and none lost antibody. These results are very similar to those for plasma-derived vaccine. Comparison of titres of antibody to hepatitis B surface antigen (anti-HBs) showed a slightly higher level with the 10-micrograms than with the 5-micrograms dose of the recombinant vaccine. Geometric mean titres of anti-HBs after the booster dose were similar in the 5-micrograms and 10-micrograms dose recombinant vaccine groups (2,620 and 2,748 IU/l, respectively) and in the 5-micrograms plasma-derived vaccine group (3,591 IU/l) but significantly higher (9,227 IU/l) with the 10-micrograms dose of the plasma-derived vaccine. These results confirm the safety and immunogenicity of the recombinant vaccine, although further study is needed on the duration of immunity.     

The isolated presence of anti-HBc antibodies: prevalence and interpretation based on the results of viral DNA research and anti-HBs antibodies measurement after vaccination

In order to study the significance of the isolated presence of anti-HBc antibodies, we have looked for the 3 classic serological markers of the hepatitis B (HBs antigen, anti-HBs and anti-HBc antibodies) in 1,586 hospital agents who are to vaccinate in the framework of a campaign of systematic vaccination of the hospital personnel of university hospitals of Sfax for a period of 18 months. We identified subjects who presented isolated anti-HBc antibodies (33 individuals = 2.08%). In these subjects'serum, we performed a research of the DNA of hepatitis B virus (HBV) with a PCR hybridization technique using a couple of primers. One week after administration of a vaccine dose, we also measured anti-HBs antibodies in their sera. Among the tested 18 personnel with anti-HBc isolated antibodies, 11.1% had low rates of anti-HBs antibodies indicating that there is presumably primary antibody response and therefore a false positivity of anti-HBc antibodies in pre-vaccinal serology; while 11.1% others had higher rates of anti-HBs antibodies corresponding to a secondary antibody response, which witness a previous HBV immunisation. The research of the HBV-DNA was positive in 11.1% of tested personnel, testifying a presumably chronic portage of the virus with low rates of the HBs antigen undetectable with the serological techniques. For the remainder subjects with isolated anti-HBc antibodies (66.7%), the interpretation remains ambiguous.     

Low-dose vaccination against hepatitis B in children: one-year follow-up

Six hundred forty-three children, negative for markers of hepatitis B virus (HBV) infections, were given three X 2-micrograms doses of Merck, Sharp and Dohme (MSD) plasma derived hepatitis B vaccine (H-B-Vax) at monthly intervals. Twelve months after the first dose of vaccine, antibody to hepatitis B surface antigen (anti-HBs) was detected in 89% of children by radioimmunoassay (RIA) and in 83% by enzyme immunoassay (EIA). Seroconversion rates and anti-HBs titres were significantly greater in 1-4-year-olds than in older children (p less than 0.01). Eighteen children with no anti-HBs or other markers of HBV at this time were given 10 micrograms of vaccine and tested one month later. Seventeen developed anti-HBs, 12 at levels consistent with an anamnestic response. Forty-nine HBV-marker-negative children seroconverted for antibody to hepatitis B core antigen (anti-HBc) in the 8-month period before or the 12-month period following vaccination. Forty-six of these children were positive for anti-HBs, and one has been confirmed as a chronic carrier of hepatitis B surface antigen (HBsAg). Three cases of clinical hepatitis B in children have been seen in the community since the vaccination programme began. Two of these were amongst the estimated 5% of children who were not vaccinated. The third was in a vaccinee and occurred 4 1/2 months after the last dose of vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nine-year follow-up study of a plasma-derived hepatitis B vaccine in a rural African setting

One hundred and one of 255 recipients of a plasma-derived hepatitis B vaccine were evaluated in 1990, 9 years after the first vaccine dose in a study in Zambia to evaluate the efficacy of one, two, or three doses. In 1983, 2 years after the first vaccine dose, antibody to the hepatitis B surface antigen (anti-HBs) had been detectable in 90 of these 101 participants (89%). In 1990, anti-HBs was still detectable in 72 of 101 (71%), and was present at a protective level ( ≥ 10 mlU ml) in 68 of 101 (67%). Although the original vaccine study elicited a protective level of antibody in a greater percentage of children and adolescents than in adults, there were no significant differences among the three groups at 9 years. (In 1990, anti-HBs was still detectable in 52 of 70 [74%] who had had no serologic markers of the hepatitis B virus in 1981, and a protective level was detected in 47 of 70 [67%].) A protective level of anti-HBs was detected in 1990 in 26 of 36 (72%) recipients of three doses and in 23 of 31 (74%) recipients of two doses; the slightly lower prevalence among recipients of one dose (19 of 34 [56%]) was not statistically significant. However, between the years 1983–1990, hepatitis B virus infections had occurred in one of 36 (3%) of those who had been vaccinated with three doses, one of 31 (3%) vaccinated with two doses, and eight of 34 (24%) of those vaccinated with one dose (P < .02 for either two or three doses compared with one dose). These data support the long-term immunogenicity and protective efficacy of a two- or three-dose regimen of the hepatitis B vaccine in a rural African setting. © 1993 Wiley-Liss, Inc.     

Evaluation of Immune Response to Hepatitis B Vaccine in Healthcare Workers at a Tertiary Care Hospital

Purpose: Healthcare workers (HCWs) are at high risk of acquiring hepatitis B virus (HBV) infection through occupational exposure which is preventable through hepatitis B vaccination. In the current study, the response to HBV surface antigen (HBsAg) vaccine was assessed in a selected group of HCWs by testing for antibodies against HBsAg (anti-HBs). Methods: Blood samples were collected in all HCWs, who have received the complete schedule of hepatitis B vaccination and anti-HBs levels, were assessed quantitatively in sera using ELISA. Results: The age range of the study participants was 20–55 years. The mean months after the last dose of vaccination were 60.36. Among the 85 participants, 96.5% (n = 82) have protective immunity to hepatitis B. The anti-Hbs response was similar in both male and female (P > 0.05). There was a decline in immune response as the age was increasing (P < 0.05). The results of the study found a significant decline in the immune response with time (P < 0.05). The anti-Hbs response was declined with smoking habit (P < 0.05) and with increasing body mass index (P < 0.05). Conclusion: Post-HBsAg vaccination immunity to hepatitis B was 96.5% in HCW and was similar to that of global rates. Increasing age, time period, smoking habit, and overweight were associated with decreased immunity. Many studies are needed in developing newer HBV vaccines with very high immunogenicity. Giving highly immunogenic vaccine to HCWs will ensure safety at work by reducing nosocomial transmission which is very much desired in a resource-limited country.     

Induction of peripheral blood T follicular helper cells expressing ICOS correlates with antibody response to hepatitis B vaccination

T follicular helper (TFH) cells, a critical subset of CD4⁺ T cells, provide help to B cells during the procession of the humoral immune response in the germinal center (GC) and extrafollicular sites. CXCR5⁺CD4⁺ T cells in human circulating blood, referred to herein as peripheral TFH (pTFH) cells, share phenotypes and functional properties with TFH cells in GC. Hepatitis B vaccine protects about 60% of the chronic hepatitis C patients from hepatitis B. The immunological bases that lead to the induction of protective antibody response is not well understood. In the present study, the pTFH cells subsets were determined in 18 healthy controls (anti-HBs ≥ 100 mIU/mL; HC), 21 nonresponders (anti-HBs < 10 mIU/mL; NR), and 23 weak responders (10 mIU/mL ≤ anti-HBs < 100 mIU/mL; WR) of chronic hepatitis patients upon routine hepatitis B vaccination. Though the frequency of the pTFH cell was equivalent in HC, WR, and NR, ICOS⁺pTFH cells in HC underwent expansion with increased IL-21 secretion and production of serum anti-HBs response at 4 weeks after a full course of hepatitis B vaccination. These changes were not shown in both NR and WR. Analysis of ICOS⁺pTFH cells represents a novel cellular determinant of the hepatitis B vaccine–induced humoral immune response, which may have relevance for design of hepatitis B vaccine.     

Hepatitis B Virus Antibody Levels 7 to 9 Years after Booster Vaccination in Alaska Native Persons

Hepatitis B antibody persistence was assessed in individuals who had previously received a vaccine booster. We measured hepatitis B surface antigen antibody (anti-HBs) levels 7 to 9 years post-hepatitis B booster in individuals with primary vaccination at birth. While 95 (91.3%) of 104 participants had detectable anti-HBs (minimum, 0.1 mIU/ml; maximum, 1,029 mIU/ml), only 43 (41%) had protective levels of ≥10 mIU/ml. Pre- and week 4 postbooster anti-HBs levels were significant predictors of hepatitis B immunity at follow-up (P < 0.001). Almost all participants had detectable anti-HBs 7 to 9 years after the hepatitis B vaccine booster, but less than half had levels ≥10 mIU/ml.     

Immunogenicity in chimpanzees of experimental hepatitis B vaccines prepared from intact hepatitis B virus,purified polypeptides,or polypeptide micelles

The immunogenicity of three experimental hepatitis B vaccines was evaluated in chimpanzees. Although no antibody to hepatitis B surface antigen (anti-HBs) was detected in two chimpanzees that received an aqueous polypeptide vaccine subcutaneously, a strong anti-HBs response was observed two and ten weeks, respectively, following challenge with hepatitis B virus. Inoculation of two additional chimpanzees with a micellar preparation of these polypeptides by the intravenous route resulted in anti-HBs production in one of the chimpanzees. Two chimpanzees inoculated subcutaneously with an aqueous vaccine of formalin-inactivated intact hepatitis B virus developed anti-HBs in low titers, but the development of antibody to the hepatitis B core antigen following challenge inoculations suggested that subclinical HBV infections may have occurred despite prior vaccination.     

A prospective study of in vitro anti-HBs producing B cells (spot-ELISA) following primary and supplementary vaccination with a recombinant hepatitis B vaccine in insulin dependent diabetic patients and matched controls.

A prospective study of the immune response after hepatitis B vaccination was carried out in 32 insulin dependent diabetes mellitus (IDDM) patients and their age and sex matched healthy controls. A sensitive, immunoenzymatic technique was used, able to detect in vitro specific antibody production by mitogen stimulated individual B cells. In-vivo serologic response after vaccination with a standard scheme (0, 1 and 6 months) of 20 micrograms recombinant hepatitis B (HB) vaccine was significantly impaired in the IDDM patients both with respect to the number of nonresponders (25 versus 3%, P less than 0.05) and antibody titers reached (1,377 vs. 9,060 IU/L, P less than 0.05). The total number of in vitro IgM- and IgG-class immunoglobulin producing B cells as detected by the spot-ELISA, was found to be comparable in both groups. Specific IgG anti-HBs (and to a lesser extent IgM anti-HBs) showed impairment in the diabetic population as a whole. The number of IgG anti-HBs producing B cells was markedly depressed one month following vaccination, which is probably a reflection of homing of B cells outside the circulation. Responding subjects were identified early during their vaccination by the detection of in vitro anti-HBs production using the spot-ELISA. Non-responding healthy subjects and IDDM patients as a group showed a low number of IgG anti-HBs spots, suggesting a reduced specific memory B cell frequency. In 13 of 15 hypo- and nonresponders with positive IgG anti-HBs spots supplementary vaccination(s) resulted in improved anti-HBs levels.     

Absence of anti-hepatitis B surface antibody after vaccination does not necessarily mean absence of immune response

A small number of subjects vaccinated against hepatitis B do not produce anti-hepatitis B surface (HBs) antibody levels detectable by commercial assays. Others lose detectable anti-HBs at some time after vaccination. The absence of clinical hepatitis despite potential exposure to hepatitis B virus (HBV) in both kinds of subjects suggests that they might be protected by low antibody levels. However, besides anti-HBs, T helper response and memory cells which may be induced by the vaccine are certainly also important for immunity against HBV. In the present study, samples from vaccinated subjects, found to be anti-HBs negative in an initial assay, subsequently showed positive results in, respectively, 25%, 36% and 38% of the cases, when a second, third and fourth assay was used. In addition, 360 samples from “nonresponders” and from vaccinees who had lost anti-HBs, the reactivity of which was under the enzyme-linked immunoassay-cut-off value were compared to that of nonvaccinated controls. The absorbances were found to be significantly higher in the nonresponders (0.038) and in the vaccinees having lost anti-HBs (0.041), than in the controls (0.025). Such findings contribute to explaining why so-called nonresponders as well as vaccinees who have lost anti-HBs nevertheless appear to be protected. Received: 16 June 2000     

Significance of isolated anti-HBc seropositivity by ELISA: implications and the role of radioimmunoassay.

Hepatitis B virus (HBV) surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) are excellent markers for HBV infection and its immunity. The significance of isolated antibody to HBV core antigen (anti-HBc) seropositivity is not certain. To elucidate this, sera from 638 Chinese adult subjects, aged 18-52 years, seronegative for both HBsAg and anti-HBs, were tested for anti-HBc. Fifty-one (8%) were found to have an isolated anti-HBc seropositivity by ELISA, and all were negative for IgM-anti-HBc. The anti-HBc persisted in all subjects who attended follow-up for hepatitis B vaccination (n = 48) for a period of 8 months. These 48 subjects received 3 doses of hepatitis B vaccine (HB-VAX, 10 micrograms or 20 micrograms) at 0, 1, and 6 months: 72.9% developed a primary anti-HBs response (suggestive of a false-positive anti-HBc seropositivity), 4.2% developed an anamnestic or secondary anti-HBs response, and 22.9% did not develop an anti-HBs response. Increasing the cutoff point of the ELISA or reconfirmation with radioimmunoassay (RIA) reduced only a minor half of the false positives. This low specificity of anti-HBc ELISA/RIA, together with the high rate of anti-HBs response to hepatitis B vaccine, indicates that subjects with isolated anti-HBc seropositivity should be included in vaccination programs.     

Hepatitis B vaccination of immunosuppressed heart transplant recipients with the vaccine Hepa Gene 3 containing pre-S1, pre-S2, and S gene products

The antibody response of immunosuppressed heart transplant recipients to vaccination with the hepatitis B (HB) virus vaccine Hepa Gene 3 (HG-3), containing HB virus pre-S1, pre-S2, and S gene products, was examined. Three heart transplant recipients who had been vaccinated preoperatively against HB responded well to the vaccination. Five of 38 patients (13.2%) vaccinated postoperatively before HG-3 vaccination with the second-generation vaccine Gen-H-B-Vax-D (37 without and 1 with detectable anti-HBs response) and 3 of 24 (12.5%) without previous HB vaccination developed protective anti-HBs titers (greater than 10 U/1) after immunization with the HG-3 vaccine. The l low response rate (8/62, 12.9%) found for postoperatively vaccinated patients indicates that heart transplant recipients should be vaccinated against HB before immunosuppressive medication.Abbreviations HB hepatitis B - HG-3 Hepa gene 3     

Vaccination against hepatitis B virus at the Lyon Pasteur Institute. A seven-year evaluation]

Results of immunization against hepatitis B among Pasteur Institute staff members are reported. Prior to immunization, 439 subjects were tested for hepatitis B virus (HBV) markers, including HBs antigen, anti-HBs antibody, and anti-HBc antibody (Ausria, Ausab, Corab assays; Abbott). Forty-seven subjects tested positive for anti-HBs antibody. 317 subjects negative for all the HBs markers studied were given three intramuscular doses of Hevac B (Pasteur vaccins) at one-month intervals. Anti-HBs antibodies were assayed after the third injection with the following results: mean titer, 1,454 mIU/ml, standard deviation, 5,349 mIU/ml, and range, 4 to 41,100 mIU/ml. Anti-HBs titers above 10 mIU/ml were found in 879.4% of subjects. Non-responders and weak responders (anti-HBs titer under 10 mIU/ml) were given a fourth dose of vaccine. Ultimately, after the last (third of fourth) injection 97.6% of subjects had protective antibody titers. No case of HBV infection was seen during the seven-year follow-up period.     

Acute hepatitis B viral infection in a patient with anti-HBs.

We report a patient with antibody to hepatitis B surface antigen (anti-HBs) but no antibodies to other hepatitis B virus components, who developed acute symptomatic type B hepatitis. The possible explanations for this unusual serological pattern are 1) the antibody-positive status, which developed against only a subdeterminant of hepatitis B surface antigen (HBsAg), arose naturally or as the result of cross-reaction with a variety of antigens; and 2) seroconversion to anti-HBs occurred in response to surface antigen of a mutant strain of hepatitis B virus (HBV). This anti-HBs positivity, in the absence of antibody to hepatitis B core antigen, does not provide natural immunization against HBV infection, and so is not protective. Individuals who are positive to anti-HBs antibody alone which is not elicited by HBV vaccine, should be vaccinated against possible HBV infection.     

Immunogenicity of a recombinant pre-S2-containing hepatitis B vaccine versus plasma-derived vaccine administered as a booster

GenHevac B Pasteur is a recombinant hepatitis B vaccine derived from a mammalian cell line and containing HBs as well as pre-S2 antigens. Its immunogenicity was compared to that of the plasma-derived vaccine Hevac B Pasteur in a population primovaccinated 5.5 years earlier with four injections of the same plasma vaccine. The booster injection with either GenHevac or Hevac was administered to 295 subjects with residual anti-HBs titres below 500 IU/l (group 1: 0–9; group 2: 10–99; group 3: 100–499 IU/l). After four weeks, GenHevac had induced higher anti-HBs responses than Hevac in all groups, particularly among the low responders of group 1. Response to the vaccine occurred earlier with GenHevac. Mean anti-pre-S2 production was moderate in all groups for both vaccines (GenHevac: 60 IU/l; Hevac: 31 IU/l) and was not found in the 32 subjects who produced less than 100 IU/l anti-HBs. The results of the present study indicate that GenHevac is at least as immunogenic as Hevac.     

Regulation of the neutralizing anti-hepatitis B surface (HBs) antibody response in vitro in HBs vaccine recipients and patients with acute or chronic hepatitis B virus (HBV) infection

Antibodies directed to the HBs antigen indicate viral clearance and the development of life-long immunity in patients that recovered from HBV infection. In HBs antigen vaccine recipients anti-HBs antibodies provide protective immunity. However, little is known about the regulation of this HBs-specific antibody response. The existence of anti-HBs-secreting B cells was demonstrated using the highly sensitive ELISPOT technique compared with conventional ELISA in serum and cell culture supernatants. In the peripheral blood of patients with acute self-limited hepatitis B, HBs-specific B cells were demonstrated with a high frequency despite undetectable anti-HBs serum antibodies. HBV-immunized patients that had recovered from infection and vaccine recipients had significantly lower frequencies, whereas chronic HBV carriers and negative controls showed no anti-HBs-secreting B cells. Coculture experiments of isolated B and T cells revealed that the anti-HBs antibody response was restricted to the presence of T helper cells, but not to identical HLA class II molecules. Allogeneic T cells derived from vaccine recipients or chronic HBV carriers stimulated the HBs-specific B cell response in HBs vaccine recipients. Otherwise, isolated T helper cells could never provide sufficient help to induce the HBs-specific B cell response in chronic HBV carriers. Furthermore, peripheral blood mononuclear cells (PBMC) of six out of 10 vaccine recipients, one out of five HBV-immunized patients, but of no chronic HBV carrier showed a proliferative response to different HBs antigen preparations. This study demonstrated a high frequency of circulating anti-HBs-producing B cells in the early phase of acute HBV infection, but a lower frequency of HBs-specific B cells years after resolution of HBV infection. In chronic HBV carriers, however, deficient HBs-specific T and B cell responses were observed.