Antibody responses in human being to pre-S2 and related hepatitis B virus-envelope antigens in vivo and in vitro

Although hepatitis B (HB) virus-associated pre-S2 Ag may be important in facilitating the uptake of virions into hepatocytes, it is not clear whether the anti-pre-S2 antibody plays a substantial role in the protection from infection in man. The mechanisms underlying the nonresponsiveness to the HB vaccine are not clear. To evaluate the immunological background in nonresponders to pre-S2 Ag, HLA-DR/DQ antigens and the production of antibodies to pre-S2 Ag and HBs Ag were estimated in vitro on medical healthy personnel. Ninety-one males and 213 females were vaccinated with pre-S2 Ag positive plasma-derived HB vaccine three times. Four months after the third vaccination, blood was withdrawn for pre-S2 antibody test by ELISA. Antibodies to pre-S2 Ag were found in 19.8% of the individuals. Nonresponders were observed at a higher frequency in males than females, and they were seen more frequently in the elderly than young individuals. In aged subjects, aging seemed to be the major factor in their unresponsiveness. A high frequency of HLA-DR4.DRw53.DQw3 haplotype was observed in the subjects with nonresponsiveness against pre-S2 Ag. In order to induce the secretion of anti-HBs antibody, we investigated the effect of simultaneous administration of HBs Ag and immunoglobulin containing anti-HBs antibody on the antibody responses in vitro. In vitro stimulation of mononuclear cells from 10 individuals who failed to respond or responded poorly to HB vaccine induced a significant amount of anti-HBs antibody in 5 cases, whereas stimulation with HBs Ag alone failed to induce the antibody secretion in most cases.     

Dissociated antibody responses to the S and pre-S2 regions of the hepatitis B virus after vaccination in hemophiliacs

The membranes of hepatocytes and the pre-S2 envelope protein of the hepatitis B virus (HBV) contain binding sites for polymerized human albumin, which is thought to act as a link between HBV and hepatocytes. Hence, anti-pre-S2 antibodies should prevent HBV uptake by the liver, and there is indeed preliminary evidence that they protect chimpanzees from HBV infection. To evaluate whether a plasma-derived vaccine containing the pre-S2 sequence induced an anti-pre-S2 response in 105 vaccinated hemophiliacs, anti-pre-S2 was measured in parallel with antibody to hepatitis B surface antigen (anti-HBs). Eighty-five percent of the hemophiliacs had both anti-pre-S2 and anti-HBs when vaccination was completed, 13% had anti-HBs alone, and 2% (two cases) had anti-pre-S2 alone. Eighty-seven percent of anti-pre-S2-positive hemophiliacs compared with only 50% of anti-pre-S2-negative hemophiliacs (P less than 0.001) developed high anti-HBs titers (greater than or equal to 1,000 mlU/ml). This study demonstrates, therefore, that the antibody responses to the S and pre-S2 regions of HBV may be dissociated after vaccination in hemophiliacs and that higher anti-HBs titers are attained in anti-pre-S2-positive hemophiliacs.     

Failure of vaccination against hepatitis B with Gen H-B-Vax-D in immunosuppressed heart transplant recipients

Summary Some 86 heart transplant recipients under immunosuppressive therapy were vaccinated against hepatitis B using the vaccine Gen H-B-Vax-D, but 95.3% failed to develop protective levels of HBs-specific antibody (more than 10 U/1) after the third vaccination.Abbreviations HBsAg hepatitis B surface antigen; U/I units/ liter - HBV hepatitis B virus - GMT geometric mean titer - ELISA enzyme-linked immunosorbent assay     

Monoclonal antibody recognizing pre-S(2) epitope of hepatitis B virus: characterization of pre-S(2) epitope and anti-pre-S(2) antibody

A hybrid cell line producing monoclonal antibodies recognizing an epitope encoded by the pre-(S)2 region of hepatitis B virus (HBV) genome was obtained by fusion of mouse myeloma cells with lymphocytes from mice immunized with HBV. The monoclonal antibody Mo-F124 secreted from the hybrid line reacted with the pre-S(2) epitope expressed on the surface of both viral and recombinant HBsAg particles--pre-S(2) and S gene product--localised on 34 kD glycoprotein of the viral envelope. The pre-S(2) epitope was sensitive to digestion with V8 protease from Staphylococcus aureus. The enzyme abolished reactivity with Mo-F124 and polymerized human serum albumin (pHSA) binding activity of recombinant particles. Mo-F124 antibody was used to develop highly sensitive radioimmunoassays for determination of pre-S(2) epitope and anti-pre-S(2) antibody in sera of hepatitis B patients. Detection of a pre-S(2) epitope by the monoclonal antibody-based assay in the early phase of acute HBV infection correlated well with the presence of markers of active viral replication (HBeAg, HBV DNA). The appearance of anti-pre-S(2) antibody, usually in the third month after onset of symptoms, was followed by elimination of circulating HBsAg and seroconversion to anti-HBs in all tested cases of uncomplicated acute hepatitis followed by recovery. Anti-pre-S(2) response was not observed in patients with chronic hepatitis B or acute HBV infection progressing to chronic disease. The observed correlation of anti-pre-S(2) response with recovery suggests that the pre-S(2) epitope may represent one of the epitopes inducing antibodies that neutralize the hepatitis B virus.     

HLA-DRB1*07,13等位基因对乙肝疫苗免疫效果影响的研究

目的:探讨机体HLA-DRB1*07,13等位基因对基因重组乙肝疫苗免疫效果的影响.方法:选取完成基因重组乙肝疫苗全程接种(10 μg/次,0、1、6月)的广西籍汉族健康大学生896名,于末次接种疫苗后的第6个月采血检测血清抗-HBs水平,对无或低应答者再次接种基因重组乙肝疫苗20 μg,4周后筛选出无或低应答者99名及初次检测中或强应答者136名作为研究对象,应用PCR-SSP技术对研究对象外周血HLA-DRB1*07,13等位基因进行检测.结果:HLA-DRB107在无或低应答组中的表达频率为16.16%,显著高于中或强应答组的表达频率(4.41%)(P＜0.05);HLA-DRB1*13在无或低应答组和中或强应答组的表达频率分别为1.01%和3.68%,两组比较无统计学差异(P＞0.05).结论:基因重组乙肝疫苗无或低应答与HLA-DRB1*07基因密切相关;而HLA-DRB1*13对乙肝疫苗的免疫应答无明显影响.     

In vitro immune responses to hepatitis B surface antigen (pre-S2 and S) following remote infection by hepatitis B virus in humans

In this report we evaluate the human immune response to hepatitis B surface antigen (HBsAg) following remote infection with hepatitis B virus (HBV). HBsAg-reactive lymphocytes can be readily demonstrated in the peripheral blood of individuals with established immunity following infection with HBV.In vitro stimulation with small doses of plasma-derived HBsAg, yeast-derived HBsAg (S region) or pre-S2 peptide will induce specific IgG to HBsAg (anti-HBs) in the absence of a polyclonal increase in total IgG. The pre-S2 peptide will stimulate, in a T cell-dependent fashion, thein vitro production of anti-HBs with specificity for the S domain. This anti-HBs production is mediated by pre-S2-stimulated soluble T-cell factors. Peripheral blood mononuclear cells from individuals with established immunity proliferate to the yeast-derived HBsAg but not to the plasma-derived HBsAg or pre-S2 peptide. The chronic HBsAg carriers do not produce anti-HBs following stimulation with HBsAg regardless of the source or component of antigen used. Different study protocols failed to demonstrate HBsAg-specific responses in the peripheral blood mononuclear cells of chronic carriers.     

Seroprevalence of Hepatitis-B infection amongst Taiwanese university students 18 years following the commencement of a national Hepatitis-B vaccination program

In Taiwan, the nation-wide Hepatitis-B virus (HB) vaccination program was first launched in July 1984 and was directed to those infants born to hepatitis B surface antigen (HBsAg) carrier mothers in Taiwan. From July 1986 onwards, all infants born in Taiwan were immunized against HB. This study examined the HB-infection status amongst students at a Taiwanese university 18 years subsequent to the implementation of universal HB vaccination. A total of 1,969 new university entrants in 2005 were grouped into 1 of 3 distinct birth cohorts according to their HB-vaccination schedule (cohort-1 students born prior to July 1, 1984; cohort-3 students born subsequent to June 30, 1986) and were examined for their serum HBsAg, antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc) status. Immunity arising from vaccination was defined as an anti-HBs level 10 mIU/ml. We observed a trend toward a decreasing anti-HBc-positive rate and a decreasing HBsAg carrier rate from, respectively, 26.5 and 8.7% for cohort-1 to 4.7 and 1.7% for cohort-3 students. The prevalence of students featuring seronegativity for all three HB markers increased from 12.3% for cohort-1 to 48.8% for cohort-3 individuals. Amongst the 1,695 subjects revealing seronegativity for HBsAg and anti-HBc, their anti-HBs level was analyzed according to their birth year. The prevalence of students featuring a non-protective anti-HBs level increased from 11.9% for birth-year 1984 individuals to 48.2% for birth-year 1987 students. The introduction of HB vaccine has effectively reduced the transmission of HBV infection in Taiwan, 18 years subsequent to the commencement of the universal HB-vaccination program. A "waning-off" effect of anti-HBs seropositivity acquired from the HB vaccination program has also been observed.     

HLA linked immune response to S and pre-S2 gene products in hepatitis B vaccination

In order to detect a possible HLA linked genetic control of human immune responses to hepatitis B virus, forty healthy adult persons of the same age typed for HLA-A, -B and -DR antigens, were vaccinated against virus hepatitis B and sequentially tested for anti-HBs and anti-pre-S2 antibodies. They received three injections of Hevac-B Pasteur vaccine, the second 1 month and the third 3 months after the first. Following the third immunization, 38 individuals (95%) had a protective level of anti-HBs antibodies and 17 (42.3%) had a positive level of anti-pre-S2 antibodies. HLA-A11 antigen was significantly more frequent (pc = 0.007) among anti-HBs high responders than low responders. In addition, anti-HBs high responders were more frequently HLA-DR1, and less frequently HLA-DR4 and DR7 positive; corrected values, however, were not significant. Anti-pre-S2 high responders showed an apparent increase of HLA-B7, B14 or DR3 antigens, when compared to low responders (pc not significant).     

成人及新生儿乙肝疫苗免疫后15年内表面抗体水平的变化

目的描述和比较北京市15岁及以上人群(以下简称成人)及新生儿乙肝疫苗接种后的15年内抗体水平,为北京市乙肝疫苗接种策略提供参考。方法 2013年8月至2014年2月采用多阶段整群随机抽样方法在北京市1岁以上人群中抽取6 705人进行乙肝血清学流行病学调查,选择其中完成3针基因重组乙肝疫苗接种且没有进行加强免疫的成人和新生儿为研究对象,描述和比较成人和新生儿接种乙肝疫苗后15年抗-HBs阳性率和抗-HBs滴度变化。结果共纳入符合入组标准的新生儿和成人分别为463和129人。基于中国目前15~59岁人群自限性感染率估计为30%,成人接种后0~4、5~9和10~15年的抗-HBs阳性率仍可分别保持在58.6%、62.5%和48.4%,呈现平稳下降的趋势;对应的抗-HBs滴度中位数分别为288.8、120.6和62.6 m IU/m L。新生儿接种人群3个时间段的抗-HBs阳性率分别为83.3%、47.3%和43.5%;抗-HBs滴度中位数分别为71.8、8.9和6.7 m IU/m L;成人接种乙肝疫苗后5~15年的抗-HBs滴度及阳性率均高于新生儿。结论成人和新生儿接种乙肝疫苗15年内可获得良好的保护。     

Immunity to hepatitis B: analysis of antibody and cellular responses in recipients of a plasma-derived vaccine using synthetic peptides mimicking S and pre-S regions.

The potential of a panel of synthetic HBsAg peptides as components of a synthetic hepatitis B vaccine was assessed. Each was used in turn as probes to analyse human immune responses to a licensed plasma-derived HBV vaccine. Both humoral and cellular responses were analysed with synthetic peptides representing residues 124-147 of the surface antigen of the virus (HBsAg) and residues 126-140 of the pre-S2 region. Antibody levels and affinities were assessed in radioimmunoassays with synthetic linear and cyclical forms of surface antigen peptides 124-137 and 139-147, with the gp30p25 polypeptide complex of HBsAg and with the linear pre-S2 peptide 126-140. Levels and affinities of antibodies to the antigens increased with time during immunization. However, antibodies binding the cyclical peptide representing amino acids 139 to 147 (C139) were present at higher levels and had higher affinities than were antibodies binding the other peptides, indicating that C139 more closely approximates a domain on the native antigen than do the other peptides. No humoral responses were measured with the pre-S2 peptide. Cellular responses were assessed by in vitro stimulation of peripheral blood lymphocytes by HBsAg and by the synthetic peptides. All vaccine recipients had demonstrable lymphocyte responsiveness to HBsAg after both second and third doses of the vaccine. Of the S and pre-S peptides used, only L124 failed to induce lymphocyte stimulation in all recipients. However, there were individual variations in both the time of initial responsiveness to peptides and in the level and time of maximal stimulation. Stimulation by native HBsAg particles, which corresponded to the appearance of anti-HBs antibody, preceded that observed using synthetic peptides. In all recipients, maximum stimulation indices with HBsAg were significantly higher than those observed with the peptides. In contrast to the absence of pre-S2 antibody, the lymphocytes from all recipients showed positive stimulation in response to the peptide representing residues 126-140 of the pre-S2 region. None of these individuals had antibodies to pre-S or an HB core peptide sequence nor did their lymphocytes respond to a synthetic peptide representing an HB core sequence.     

Detection of antibodies to pre-S2 encoded epitopes of hepatitis B virus by monoclonal antibody-enzyme immunoassay

An inhibition enzyme immunoassay (IEIA) for the detection of anti-pre-S2 antibody has been developed and used to evaluate anti-pre-S2 responses in the sera of patients recovering from acute type B hepatitis and in the sera of healthy recipients of HBV vaccine. In the assay, we used two monoclonal antibodies recognizing the nonoverlapping epitopes (pre-S2a and pre-S2b) of the pre-S2 protein of HBV envelope which compete with human anti-pre-S2 for the limited antibody-binding sites on recombinant HBsAg particles (pre-S and S gene product). Two variants of the method were assayed employing the reference pre-S2 antigen on the solid (IEIA-sp) or in the liquid phase (IEIA-lp). Two McAbs were used to detect antibodies reacting specifically with pre-S2a and pre-S2b epitopes of the pre-S2 sequence. Both variants gave similar results and were successfully used for the determination of anti-pre-s2 in sera. We demonstrated that during HBV infection as well as after vaccination against HBV both pre-S2 epitopes generate specific immune responses. Anti-pre-S2 were detected in 45.3% patients recovering from HBV infection and in 43.7% of healthy recipients of the HBV vaccine licensed in France. Anti-pre-S2a and anti-pre-S2b were detected in sera in dilutions up to 10(-5). IEIA may provide a specific and highly sensitive screening test for monitoring serum anti-pre-S2 levels during HBV infection and after immunization with HBV vaccine.     

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)     

Hepatitis B vaccination status in an at-risk adult population: long-term immunity but insufficient coverage

In France, hepatitis B (HB) vaccine has been offered to all infants since 1994, and was proposed to all children aged 11 years from 1994 to 1998. Nevertheless, HB vaccine hesitancy may result in low vaccination coverage in present-day at-risk adults. We aimed to determine HB vaccination coverage in adults attending a free testing center for sexually transmitted infections (STI). As part of routine care, three classes of data were anonymously collected from attendees over a 3-month period: results of HB serologic tests; date and number of past anti-hepatitis B virus (HBV) immunization(s) (if any) according to health records; and the risk of STI and blood-transmitted infections (BTI). The study included 735 participants (age 27.9?±?9.2; 59.9% men). According to available health records (341 participants), 56.6% had received at least three and 67.2% at least one vaccine injection(s); 57.7% had received their last injection between 1994 and 1998, reflecting the strong vaccine policy during these years. Serologic testing (in 705 participants) showed evidence of a past or active HBV infection for 33 participants; of the remaining patients, 55.3% had anti-HBs antibody titers ≥10 IU/L. This rate was not higher in participants considered at risk for STI/BTI. Of the participants who received their last vaccine injection more than 15 years previously, 90.5% had anti-HBs antibody concentrations ≥10 and 60.3% ≥100 IU/mL. HB vaccination coverage is low in this population. Most of the vaccinated participants were immunized between 1994 and 1998, suggesting a failure of catch-up immunization of adolescents and at-risk adults. Long-term seroprotection persisted among vaccinated participants.     

Comparative evaluation of the immunogenicity of yeast-derived (recombinant) and plasma-derived hepatitis B vaccine in infants.

The immunogenicity of plasma-derived (HB Vax,MSD) and recombinant hepatitis B virus (Engerix B, SK&F) vaccines was evaluated in infants born to hepatitis B virus carrier mothers. The vaccination was carried out at 1 day, 1 month, and 6 months of age using 10 micrograms of the vaccine given intramuscularly. A total of 83/88 (94.3%) and 74/79 (93.6%) of the infants receiving the plasma-derived vaccine and yeast-derived vaccine showed antibody to hepatitis B surface antigen (anti-HBs). None of the maternal factors studied apart from the HBeAg positivity corellated with vaccine failure. The yeast-derived vaccine gives marginally lower antibody titre than the plasma-derived vaccine. The group-specific anti-"a" antibody was less than 10% of the total anti-HBsAg titre. It was observed that the vaccine alone without prior administration of hepatitis B immunoglobulin is effective in perinatal infection.     

Occurrence of pre-S1 antigen in viremic and nonviremic carriers of hepatitis B surface antigen

The proteins of viral envelope, encoded by the pre-S1 region of HBV-DNA, were measured quantitatively with enzyme immunoassay using monoclonal antibodies directed to pre-S1 epitope and correlated with the expression of pre-S2 region encoded epitope and other HBV markers. In acute HBV infection, both pre-S encoded proteins were detected in sera along with markers of viral replication and disappeared shortly before complete virus clearance while high HBsAg titers were still present. Pre-S1 antigen was present in most (95.5%) symptomatic and asymptomatic chronic HBsAg carriers. There was no correlation between the presence of pre-S1 and HBeAg or HBV-DNA in serum: 73% of sera with pre-S1 determinants were anti-HBe positive, and only 25.4% were positive for HBV-DNA. Most pre-S1 activity in sera of viremic carriers was detected in fractions of sucrose gradient containing subviral 22-nm particles, and much less in those containing infectious virions. In asymptomatic, nonviremic HBsAg carriers, pre-S1 was located only on subviral 22-nm forms. Pre-S1 positive particles had no accessible pre-S2 epitope, which is recognized specifically by monoclonal anti-pre-S2 (F124) antibody. These results show that the synthesis of the large protein of HBV envelope may occur also in the absence of active viral replication, and in these cases pre-S1 encoded sequences are on subviral particles of HBsAg. Therefore, pre-S1 is not a serologic marker of infectious virus. Disappearance of pre-S1 epitopes on HBsAg occurs only before complete clearance of the virus, and this may have potential prognostic relevance.     

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.     

Active pre-exposure immunisation against hepatitis B virus: immunogenicity of hepatitis B vaccine in healthy Thai adults and children

The immunogenicity of plasma derived hepatitis B vaccine (Hevac B) was studied for active pre-exposure immunisation in 176 healthy volunteer adults and 162 randomised children who had no hepatitis B virus markers. All subjects received three injections of 5 micrograms of hepatitis B vaccine intramuscularly at one month intervals. Seroconversion at 2 months after the third dose of vaccine was 96.30 percent in the children and 92.00 percent in the adults with mean anti-HBs titres of 800 mlU/ml and 353 mlU/ml respectively. The difference of anti-HBs levels between these two groups was statistically significant (p less than 0.05). Female adults had exhibited higher immune response to HB vaccine than male adults but there was no seroconversion difference between boys and girls. There were no serious local or systemic side effects of hepatitis B vaccination. It was concluded that active immunisation with plasma derived hepatitis B vaccine in non-immune children and adults is highly effective without any serious side effects or complications. The prevention of horizontal transmission of hepatitis B virus should be done by vaccination in children since they have a much better immune response to hepatitis B vaccine than adults.     

Active immunization of homosexual men using a recombinant hepatitis B vaccine

Twenty homosexual men [13 anti-human immunodeficiency virus (HIV)-positive, seven anti-HIV negative] without HBsAg, anti-HBs, and anti-HBc were vaccinated with three 20 micrograms doses of a recombinant hepatitis B vaccine. All anti-HIV-positive homosexuals were nonresponders independent of the initial number of CD4-positive cells. Among seven anti-HIV-negative individuals, five responded. After three doses of the vaccine, CD4-positive cells fell in anti-HIV positive individuals by 22.4%. A similar fall in CD4-positive cells of an average 24.9% was noted in 17 matching, but nonvaccinated, anti-HIV-positive homosexuals. The study indicates that the efficacy of vaccination in anti-HIV-positive individuals is questionable. There is, however, no evidence that vaccination against hepatitis B might be harmful to anti-HIV-positive subjects.     

Efficacy and Safety of Revaccination against Tetanus,Diphtheria, Haemophilus influenzae Type b and Hepatitis B Virus in a Prospective Cohort of Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

Data on immunogenicity and safety of the recommended revaccination schedule against diphtheria, tetanus, poliomyelitis, pertussis, Haemophilus influenzae type b (Hib), and hepatitis B in adult allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients are limited. This prospective single-center cohort study (April 2014 to March 2018) included adult allo-HSCT recipients referred to a dedicated vaccinology consultation and vaccinated with the pediatric combined diphtheria, tetanus, acellular pertussis, hepatitis B virus, inactivated poliovirus, and Haemophilus influenzae type b (DTaP(±HB)-IPV-Hib) vaccine (3 doses 1 month apart, booster dose 1 year later). The proportion of responders to tetanus, diphtheria, Hib, and hepatitis B vaccine and geometric mean concentrations (GMCs) of antibodies were assessed before and up to 24 months after vaccination. A total of 106 patients were vaccinated at a median (interquartile range) time of 12.4 (10 to 18.4) months post-transplant. At 5.3 (4.8 to 6.6) and 23.1 (21.1 to 25.1) months after vaccine initiation, high and sustained rates of protective antibody titers were achieved for tetanus (97.8% [95% confidence interval (95% CI), 92.4% to 99.7%], n = 91/93 and 100% [95% CI, 92% to 100%], n = 44/44), diphtheria (94.6% [95% CI, 87.9% to 98.2%], n = 88/93 and 90.9% [95% CI, 78.3% to 97.5%], n = 40/44), Hib (96.6% [95% CI, 90.4% to 99.3%], n = 85/88 and 93% [95% CI, 80.9% to 98.5%], n = 40/43), and hepatitis B (83.5% [95% CI, 73.5% to 90.9%], n = 66/79 and 81.1% [95% CI, 64.8% to 92%], n = 30/37). Underlying disease, stem cell source, chronic graft-versus-host-disease, and extracorporeal photopheresis differentially influenced GMCs of tetanus, diphtheria, and hepatitis B antibodies after 3 doses but not in the long term (24 months). Six (5.7%) patients experienced mild side effects. The pediatric DTaP(±HB)-IPV-Hib vaccine was safe and effective in eliciting a sustained protective humoral response in adult allo-HSCT recipients. Hepatitis B revaccination might be optimized by using higher antigen doses.     

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.