Hepatitis B vaccine in infants from an endemic area: long-term anti-HBs persistence and revaccination

Persistence of anti-HBs in 156 Senegalese infants immunized with hepatitis B vaccine was studied for periods ranging from 2 to 6 years after booster dose administration. Six years after the booster dose, 90.4% of the infants had detectable anti-HBs antibodies, with 78.1% having titers higher than 10 mIU/ml. The geometric mean titer was 60 mIU/ml. Females showed higher anti-HBs values than males. In a group of 11 infants who received no booster dose, anti-HBs antibodies were detectable 7 years after the first dose. However, the geometric mean titer was lower (26 mIU/ml). Revaccination (56 infants) led to an increase of the geometric mean titer to 469 mIU/ml 2 months later. These results show that a booster injection every 5-6 years should provide adequate protective anti-HBs levels in infants.     

Immunogenicity,Safety, and Antibody Persistence at 3, 5, and 10 Years Postvaccination in Adolescents Randomized to Booster Immunization with a Combined Tetanus,Diphtheria, 5-Component Acellular Pertussis,and Inactivated Poliomyelitis Vaccine Administered with a Hepatitis B Virus Vaccine Concurrently or 1 Month Apart

An understanding of the antibody persistence elicited by a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliovirus vaccine (Tdap-IPV) after adolescent vaccination is important to optimize booster dosing intervals. Our objectives were to compare the safety and immunogenicity of Tdap-IPV coadministered with hepatitis B vaccine (HepB) and sequential administration and evaluate humoral immunity at 3, 5, and 10 years after Tdap-IPV vaccination in adolescents. This phase II randomized, controlled, and open-label study enrolled 280 11- to 14-year-old adolescents with up to 10 years postvaccination follow-up. Group 1 (n = 145) received Tdap-IPV, followed by a HepB dose 1 month later, and group 2 (n = 135) received both vaccines simultaneously. No consistent increases in solicited reactions or unsolicited adverse events occurred with coadministration. All vaccinees attained seroprotective antibody levels at ≥0.01 IU/ml for diphtheria and tetanus, at a ≥1:8 dilution for poliovirus (serotypes 1, 2, and 3), and ≥10 mIU/ml for hepatitis B at 1 month postvaccination. Clinically relevant immunologic interactions did not occur with coadministration. For pertussis, all participants achieved seropositivity levels (at or above the lower limit of quantitation), and 72.7% to 95.8% had 4-fold increases in pertussis antibodies at 1 month postvaccination. At 10 years postvaccination, the remaining participants (62.8% of the original cohort) maintained seroprotective levels of ≥0.01 IU/ml for diphtheria and tetanus, a ≥1:8 dilution for all 3 poliovirus serotypes, and 74.1% to 98.2% maintained pertussis seropositivity levels depending on the antigen tested. There were no differences between the groups. These results support the coadministration of Tdap-IPV and HepB to adolescents and suggest that vaccination with Tdap-IPV can offer protection for 10 years after an adolescent booster vaccination.     

Hepatitis B immunity in teenagers vaccinated as infants: an Italian 17-year follow-up study

We assessed the persistence of hepatitis B surface antigen antibody (anti-HBs) and immune memory in a cohort of 571 teenagers vaccinated against hepatitis B as infants, 17 years earlier. Vaccinees were followed-up in 2003 and in 2010 (i.e. 10 years and 17 years after primary vaccination, respectively). When tested in 2003, 199 vaccinees (group A) had anti-HBs <10 mIU/mL and were boosted, 372 (group B) were not boosted because they had anti-HBs ≥10 mIU/mL (n = 344) or refused booster (n = 28) despite anti-HBs <10 mIU/mL. In 2010, 72.9% (416/571) of participants had anti-HBs ≥10 mIU/mL (67.3% in group A vs. 75.8% in group B; p 0.03). The geometric mean concentrations (GMCs) were similar in both groups. Between 2003 and 2010, anti-HBs concentrations in previously boosted individuals markedly declined with GMC dropping from 486 to 27.7 mIU/mL (p <0.001). Fifteen vaccinees showed a marked increase of antibody, possibly due to natural booster. In 2010, 96 individuals (37 of group A and 59 of group B) with anti-HBs <10 mIU/mL were boosted; all vaccinees of the former group and all but two of the latter had an anamnestic response. Post-booster GMC was higher in group B (895.6 vs. 492.2 mIU/mL; p 0.039). This finding shows that the immune memory for HBsAg persists beyond the time at which anti-HBs disappears, conferring long-term protection.     

Hepatitis B vaccine: immunogenicity and follow-up including two year booster doses in high-risk health care personnel in a London teaching hospital

One hundred forty-four adult health care personnel (aged 18-62 years, median 33 years) considered at high risk of future HBV infection were vaccinated with a plasma-derived hepatitis B vaccine (20 micrograms HBVax at 0, 1, and 6 months) and followed-up for 2 years. Anti-HBs was present in only 6.9% prior to vaccination, and prescreening to detect this group would not have been cost-effective. At 9 months, 8.3% were nonresponders and a further 9% had anti-HBs levels less than 50 mIU/ml. Multivariate analysis showed that age was the single most important determinant of a poor response. In 47 of 52 individuals retested 2 years later, anti-HBs levels had fallen by 80% or more, and in four it had become undetectable. Response to a booster dose at this stage was excellent, with anti-HBs levels 3 months later much higher than at the end of the initial course. Additional booster doses of vaccine in two of the initial nonresponders at 14 and 22 months, respectively, also led to seroconversion. Although a significant proportion of health care workers in this study did not make a satisfactory response to the hepatitis B vaccine, later booster doses were very effective in subsequently increasing anti-HBs levels.     

Recombinant-yeast-derived hepatitis B vaccine in healthy adults: safety and two-year immunogenicity of early investigative lots of vaccine

We tested the safety and long-term immunogenicity of two of the early investigative lots of a recombinant-yeast-derived hepatitis B vaccine in immunocompetent adults. Three 10-micrograms doses of recombinant hepatitis B vaccine (Merck Sharp & Dohme Research Laboratories, West Point, PA) were administered by deltoid intramuscular injection at time 0, 1, and 6 months to 65 seronegative adult health workers. Following a complete three-injection course, 98% of vaccinees acquired anti-HBs, 97% at levels greater than 10 mlU/ml, and 95% maintained such "protective" antibody levels at 1 year. At 2 years, 93% retained antibody, but only 68% had levels greater than 10 mlU/ml. In those who responded to vaccination by achieving any detectable level of antibody, the peak geometric mean titer of anti-HBs, measured at 9 months, was 741 +/- 6 mlU/ml; the geometric mean titer fell to 348 +/- 6 at 1 year and to 66 +/- 7 at 2 years. Side effects were trivial, and levels of yeast antibody, as measured by radioimmunoassay, were not changed from prevaccine levels. No serious adverse effects were encountered, and neither type B nor non-B hepatitis occurred in any vaccine. These findings demonstrate that the recombinant yeast hepatitis B vaccine is safe and immunogenic but that 10 micrograms of the early investigative lots of the recombinant vaccine is less immunogenic than 20 micrograms of the plasma-derived vaccine. Recipients of early investigative vaccine lots should be considered for booster vaccination with currently available, more immunogenic vaccine lots.     

Long-Term Follow-Up of Hepatitis B Surface Antibody Levels in Subjects Receiving Universal Hepatitis B Vaccination in Infancy in an Area of Hyperendemicity: Correlation between Radioimmunoassay and Enzyme Immunoassay

The aims of the present study were to determine (i) the long-term immunogenicity and the decay rate of hepatitis B virus (HBV) surface antibody (anti-HBs) from universal hepatitis B vaccination at infancy for a healthy population in an area of hyperendemicity and (ii) whether the anti-HBs levels measured by enzyme immunoassay (EIA) were closely correlated with those assayed by radioimmunoassay (RIA) methods during long-term monitoring. A total of 1,337 apparently healthy children (696 boys and 641 girls) who were vaccinated against HBV at infancy and monitored for anti-HBs annually from 7 to 16 years of age entered the study. Serum samples were analyzed for anti-HBs by RIA at 7 to 15 years of age and were also analyzed by EIA at 13 to 16 years of age. Antibody titers were quantified in mIU/ml by EIA as well as by the ratio of the count in the sample to the count for a negative control (S/N) by RIA. In nonboosted children, the average decay of anti-HBs from 7 to 16 years of ages indicated that approximately 20% of the geometric mean titer decays per year. There was a good correlation between serum anti-HBs levels measured by the RIA and the EIA methods (r = 0.91; P < 0.0001). An equation for RIA to EIA level conversion was established: log EIA titer = −0.12 + (1.31 · log RIA S/N). The anti-HBs titers measured by EIA correlate well with the S/N assayed by RIA. The annual decay rate of the log anti-HBs level may help in planning booster immunizations for hyporesponders or individuals at risk in adolescence.     

Multicenter trial on the efficacy of HBIG and vaccine in preventing perinatal hepatitis B. Final report

In an attempt to interrupt perinatal transmission of hepatitis B, 92 infants born to HBsAg carrier mothers (49 to HBeAg-positive mothers, 30 to anti-HBe-positive with abnormally elevated ALT levels, and 13 to HBeAg/anti-HBe-negative mothers) received 0.5 ml/kg BW of HBIG at birth and at 1 month of age. Three IM injections of hepatitis B vaccine were given at 3, 4, and 9 months of life. All babies who were given the three doses of vaccine developed an active anti-HBs response: of these, 53 (62.3%) had antibody titers higher than 1,000 mIU/ml, 29 (34.2%) had levels between 100 and 1,000 mIU/ml, and the other three (3.5%) were below 100 mIU/ml. At the end of the 2-year follow-up, these three poor responders became anti-HBs negative, whereas the others still had antibody. All but three babies were protected by HBIG plus vaccine treatment. Two chronic HBV infections occurred within 6 months of life presumably because the babies were already infected when prophylaxis started. The third baby became an HBsAg carrier at 9 months of age in spite of a previous response to the vaccine. Simultaneous presence of HBsAg of y specificity and anti-HBs (anti-a) was still detectable at 24 months of age. The vaccine was well tolerated. Passive plus active immunization is an effective procedure for preventing perinatally transmitted HBV infection.     

Priming of Immunological Memory by Pneumococcal Conjugate Vaccine in Children Unresponsive to 23-Valent Polysaccharide Pneumococcal Vaccine

Pneumococcal polysaccharide vaccine (PPV) is of limited immunogenicity in infants and immunocompromised patients. Our prospective randomized controlled trial investigated whether priming with pneumococcal conjugate vaccine (PCV) induced specific immunological memory in previously nonresponders to PPV. Of a total of 33 children (2 to 18 years) with polysaccharide-specific immunodeficiency (PSI), group A (n = 16) received two doses of 7-valent PCV in a 4- to 6-week interval, and a booster dose of 23-valent PPV after one year. Group B (n = 17) received two doses of PPV in a 1-year interval exclusively. Specific antibody concentrations for serotypes 4, 5, 6B, 9V, 14, 18C, 19F, and 23F were determined (enzyme-linked immunosorbent assay) before and at 7 and 28 days after administration of the PPV booster and compared to an opsonophagocytosis assay. Of group A, 64 to 100% had antibody concentrations of ≥1 μg/ml on day 28 after the booster versus 25 to 94% of group B. Group A had significantly higher antibody concentrations for all PCV-containing serotypes already on day 7, indicating early memory response. Antibody concentrations were in accordance with functional opsonic activity, although opsonic titers varied among individuals. Pneumococcal vaccination was well tolerated. The incidence of airway infections was reduced after priming with PCV (10/year for group A versus 15/year for group B). Following a PPV booster, even patients primarily not responding to PPV showed a rapid and more pronounced memory response after priming with PCV.     

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.     

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.     

Persistence and immune memory to hepatitis B vaccine 20 years after primary vaccination of Thai infants, born to HBsAg and HBeAg positive mothers

This study assessed antibody persistence and immune memory to hepatitis B vaccine 20 y after priming with a recombinant hepatitis B virus (HBV) vaccine during infancy. Infants were vaccinated according to a 0, 1, 6 mo schedule with or without simultaneous administration of hepatitis B immunoglobulin (HBIg). Half of the subjects enrolled received an interim booster dose at year 5 (boosted) group, whereas the other half of the subjects enrolled did not (unboosted group). Antibody persistence was assessed until year 20. Immune memory was assessed by administration of a final HBV vaccine challenge dose at year 20 in a second study. At year 20, anti-HBs antibody concentration ≥ 10 mIU/ml rates and GMCs were higher among subjects in the boosted group (84.2% [16/19]; 95%CI: 60.4-96.6) when compared with those in the unboosted group [44.0% (11/25)]; 95% CI: 24.4-65.1). After the HBV vaccine challenge dose at year 20, anti-HBs anamnestic response for subjects in the unboosted and boosted groups was observed in 93.1% (95% CI: 77.2-99.2) and 100% (95% CI: 76.8-100) of subjects, respectively. The mean anti-HBs antibody concentration (GMC) was 562.0 mIU/ml (292.5-1079.7 mIU/ml) post administration of the challenge dose; this is a 28.5 fold increase from the pre- to post-challenge dose administration at year 20. This study demonstrates persistence of anti-HBs antibodies and presence of immune memory following hepatitis B vaccination for up to at least 20 y in Thailand. Immune memory was demonstrated for virtually all subjects, regardless whether they received they had received the additional HBV dose or not. The challenge dose at year 20 was well tolerated and a robust response was demonstrated. ClinicalTrials.gov Identifier: NCT00240526, NCT00774995.     

Very low dose hepatitis B vaccination in the newborn: anamnestic response to booster at four years

Seventy-eight children who had received three very low doses (1 or 2 microg) of Merck, Sharp and Dohme (MSD) plasma-derived vaccine (PDV) in early infancy were followed to approximately four years of age. Of the 70 who had responded to the initial course of vaccine with measurable anti-HBs, levels had fallen to below 10 mlU/ml in 38% of subjects given 1 microg doses and in 17% of those who had been given 2 microg doses. None of the children were positive for anti-HBc. Two weeks after 2 microg dose of MSD recombinant DNA (rDNA) vaccine all subjects had more than 10 mlU/ml of anti-HBs, with 90% exceeding 1,000 mlU/ml. A response to hepatitis B vaccine in infancy is followed by an effective immunological memory for several years, even if anti-HBs falls to low levels. The rDNA hepatitis B vaccine (MSD) in 2 microg doses is an effective booster following a primary course of plasma derived vaccine.     

Long-term follow-up of Hepatitis B Surface antibody levels in subjects receiving universal Hepatitis B vaccination in infancy in an area of hyperendemicity: correlation between radioimmunoassay and enzyme immunoassay

The aims of the present study were to determine (i) the long-term immunogenicity and the decay rate of hepatitis B virus (HBV) surface antibody (anti-HBs) from universal hepatitis B vaccination at infancy for a healthy population in an area of hyperendemicity and (ii) whether the anti-HBs levels measured by enzyme immunoassay (EIA) were closely correlated with those assayed by radioimmunoassay (RIA) methods during long-term monitoring. A total of 1,337 apparently healthy children (696 boys and 641 girls) who were vaccinated against HBV at infancy and monitored for anti-HBs annually from 7 to 16 years of age entered the study. Serum samples were analyzed for anti-HBs by RIA at 7 to 15 years of age and were also analyzed by EIA at 13 to 16 years of age. Antibody titers were quantified in mIU/ml by EIA as well as by the ratio of the count in the sample to the count for a negative control (S/N) by RIA. In non-boosted children, the average decay of anti-HBs from 7 to 16 years of ages indicated that approximately 20% of the geometric mean titer decays per year. There was a good correlation between serum anti-HBs levels measured by the RIA and the EIA methods (r=0.91; P<0.0001). An equation for RIA to EIA level conversion was established: log EIA titer=-0.12+ (1.31 . log RIA S/N). The anti-HBs titers measured by EIA correlate well with the S/N assayed by RIA. The annual decay rate of the log anti-HBs level may help in planning booster immunizations for hypo-responders or individuals at risk in adolescence.     

Long-term anti-HBs antibody persistence and immune memory in children and adolescents who received routine childhood hepatitis B vaccination

This paper presents data from two studies that evaluated 5-y and 10-y persistence of antibodies against hepatitis B (HBV) surface antigen (anti-HBs) and immune response to an HBV vaccine challenge in children and adolescents who had received three doses of a HBV vaccine in infancy as part of routine clinical practice [NCT00519649/NCT00984139]. Anti-HBs antibody concentrations ≥ 10 mIU/ml persisted in 83.3% (95% confidence interval [CI]: 78.5–87.5) and 78.3% (95% CI: 73.1–83.0) of subjects aged 7–8 y and 12–13 y, respectively 5–10 y after infant vaccination. One month postchallenge dose, 98.2% (95% CI: 95.9–99.4) and 93.7% (95% CI: 90.2–96.2) of subjects in the two age groups, respectively had anti-HBs antibody concentrations ≥ 100 mIU/ml. Overall, 99.6% (95% CI: 98–100) and 97.2% (95% CI: 94.5–98.8) of subjects aged 7–8 y and 12–13 y mounted an anamnestic response to the HBV challenge dose, which was well-tolerated. Healthy children aged 7–8 y and adolescents aged 12–13 y received three doses of a monovalent pediatric HBV vaccine (10 μg of HBsAg) before 18 mo of age. Serum samples collected before and one month post-HBV vaccine challenge dose were tested for anti-HBs antibody concentrations. Safety assessments were made for the HBV vaccine challenge dose. A three-dose childhood HBV immunization regimen induced persistence of antibodies against HBV infection for 10 y, up to adolescence. This vaccination regimen also conferred long-term immune memory against HBV as evidenced by the strong anamnestic response to the HBV vaccine challenge, despite waning anti-HBs antibody levels.     

Reactivity and immunogenicity of Engerix B, the recombinant DNA vaccine against hepatitis B

A group of 67 health workers with no markers indicating previous hepatitis B infection were vaccinated against hepatitis B with a new DNA recombinant vaccine, Engerix B (commercially manufactured by Smith-Kline-RIT, Belgium). Three injections were given according to the 0-1-6 schedule. One month after the last injection the vaccinees were tested for anti-HBs antibodies by the enzyme-linked assay. Antibody titers equal or less than 10 mIU/ml were found only in three subjects or in 4.5% of them. Titers ranging from 11 to 99 mIU/ml were found in 7 subjects (10.4%), from 100 to 999 mIU/ml in 28 (41.8%) and those equal or more than 1000 mIU/ml in 29 subjects (43.3%). It is inferred that the seroconversion rate is 95.5%. Only one subject did not develop detectable antibodies but three subjects had titers over 10000 mIU/ml. No one developed overt hepatitis B during the trial nor did the high responders experienced inapparent infections. They were tested for anti HBc with negative results. Postvaccinal reactions were mild and almost exclusively local. There were no complications. For its high immunogenicity and acceptable reactogenicity the Engerix B vaccine has a promising future.     

不同剂量乙肝疫苗与HBIG联合免疫阻断HBV母婴传播的效果对比

目的 探讨10 μg和20 μg乙肝疫苗与HBIG联合免疫阻断HBV母婴传播的效果.方法 124例HBsAg阳性孕妇所生的婴儿随机分为两组,即10 μg乙肝疫苗组和20 μg乙肝疫苗组.婴儿于出生6h内及30 d分别注射200 IU HBIG,同时分别于出生24 h内、1个月及6个月注射3次10 μg或20 μg重组酵母乙肝疫苗.检测婴儿出生时以及1岁时血清HBV标志物.结果 两组新生儿血清HBsAg、HBeAg及抗-HBe阳性率与滴度之间差别均无统计学意义（P＞0.05）.所有新生儿血清HBV DNA水平均小于检测下限（500 U/ml）.出生12个月时,所有124例婴儿血清HBsAg和HBeAg检测结果均为阴性;血清HBV DNA水平均在检测下限以下;10 μg和20 μg乙肝疫苗组血清抗-HBs阳性率分别为90.3％和96.8％,差异无统计学意义（P＞0.05）;抗-HBs水平分别为325.5±342.2 mIU/ml和463.7±353.3 mIU/ml,后者显著高于前者（P=0.01）.而且,20 μg乙肝疫苗组产生高应答抗-HBs（＞ 100 mIU/ml）的比例显著高于10μg乙肝疫苗组（P =0.035）.结论 20 μg乙肝疫苗联合HBIG方案阻断HBV母婴传播的效果优于10 μg乙肝疫苗联合HBIG方案.     

Accelerated schedule of hepatitis B vaccination in patients with hemophilia

Early development of immunity after hepatitis B vaccination is particularly important for patients such as hemophiliacs, at high risk for acquiring hepatitis B from potentially infectious plasmaderived concentrates. The purpose of this study was to evaluate whether or not protective antibody titers could be achieved quickly and maintained in hemophiliacs by an accelerated vaccination schedule. A yeast-recombinant hepatitis B vaccine (Engerix B, SKF Ritt) was given subcutaneously in the deltoid region and repeated 2 and 6 weeks later to 85 hemophiliacs negative for hepatitis B virus (HBV) markers. After the first 22 patients had been enrolled, a modification of the schedule involving a fourth booster dose 24 weeks after the first dose of vaccine was applied to the next 63 consecutive vaccinees. Fifty-three percent of vaccinees had antibody titers to hepatitis B surface antigen (anti-HBs≥ 10 mlU/ml) by week 6, even though the mean titers of anti-HBs were somewhat lower than those achieved historically in normal individuals. The protection rate had increased to 87% by week 10, one month after the third dose of vaccine, and to 93% by week 24. One year after starting vaccination, the rate for the vaccinees who did not receive the fourth booster dose was 71%, and 96% for those who did receive the fourth dose, with only 2 patients not responding despite the booster dose. It is concluded that even though the accelerated schedule of immunization produced rapidly high rates of protective antibody titers, a booster dose is required to obtain higher titers and provide more persistent immunity.     

Immunogenic effect of hepatitis B vaccine in children: comparison of two- and three-dose protocols

The immunogenic effect of hepatitis B vaccine was evaluated in 183 seronegative infants from Senegal. Seventy-two seronegative infants received two 5-micrograms doses of vaccine at a two-month interval and 111 seronegative infants received three 5-micrograms doses at one-month intervals. All the children had a booster dose one year after the first injection of vaccine. No difference between the two groups was observed in the seroconversion rate (93.1% and 94.6%, respectively); in the proportion of high anti-HBs titer; or in the anti-HBs geometric mean titer (82 and 92 mIU/ml, respectively). These results demonstrate that two doses of 5 micrograms of hepatitis B vaccine are sufficient in infants to obtain a high immunogenic effect.     

Responses to a Conjugate Pneumococcal Vaccine in Preterm Infants Immunized at 2, 3, and 4 Months of Age

Preterm infants are at an increased risk of invasive pneumococcal disease infection and, additionally, have a diminished response to Haemophilus influenzae type b (Hib) conjugate vaccines. There are little data examining the response of preterm infants to a seven-valent pneumococcal conjugate vaccine (PCV7). We examined the responses of preterm infants immunized at 2, 3, and 4 months of age to PCV7. A total of 133 preterm and 54 term infants were immunized with PCV7 and the Neisseria meningitidis group C (MCC), diphtheria, tetanus, pertussis, polio, and Hib vaccines. Pneumococcal serotype-specific IgG was measured by enzyme-linked immunosorbent assay (ELISA) pre- and postimmunization and at 12 months or following a booster of PCV7. Term and preterm responses were compared using linear and logistic regression analyses. Term infants had higher preimmunization geometric mean concentrations (GMCs) for all serotypes. Preterm infants had lower postimmunization GMCs for serotype 23F. Gestational age affected postimmunization GMCs for serotypes 4, 6B, and 23F. Preterm infants were as likely to have levels of ≥0.35 μg/ml as term infants for all serotypes except 23F. The proportions of infants with titers of ≥0.35 μg/ml for all 7 serotypes were comparable between groups. A total of 28 of 29 term infants who received a booster had levels of ≥0.35 μg/ml for all serotypes. One infant had undetectable levels for serotype 6B. Of the 32 preterm infants boosted, 9 had levels of <0.35 μg/ml for 1 serotype, and 1 had levels of <0.35 μg/ml for 2 serotypes. In nonboosted infants, GMCs for all serotypes except 6B had fallen by 12 months of age. These results support the need for a booster dose in the second year of life.The primary immunization schedule of the United Kingdom (UK) is continually evolving. While a vaccine may be demonstrated to be immunogenic in one population when administered according to one schedule, apparently, minor changes to that schedule can have an adverse effect on vaccine response. Preterm infants are at an increased risk of many of the infections we immunize against, for example, pertussis (9). Almost half the children who develop pertussis are under 4 months of age (9). Preterm infants are currently recommended to be vaccinated at the same chronological age as term infants rather than at the same age postconception.The UK primary immunization schedule in place between September 2004 and September 2006 consisted of a combined vaccine against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type b (diphtheria-tetanus-acellular pertussis [DTaP]/inactivated polio vaccine [IPV]/Haemophilus influenzae type b [Hib]) (Pediacel; Aventis Pasteur MSD) and a conjugate vaccine against Neisseria meningitidis group C (MCC) given at 2, 3, and 4 months of age, with no booster in the second year of life (5). In 2002, the chief medical officer advised that children under 2 years of age at risk of invasive pneumococcal disease (IPD) should receive three doses of the seven-valent pneumococcal conjugate vaccine (PCV7; pneumococcal capsular polysaccharide conjugated to the carrier protein CRM₁₉₇), with their primary immunizations followed by a booster in the second year of life (4). Infants were considered to be at increased risk of IPD if they had a chronic respiratory, cardiac, renal, or liver disease or an immunodeficiency. Many preterm infants are included in these categories.A postal questionnaire survey of 73 UK neonatal intensive care units highlighted the fact that many preterm infants who are at an increased risk of IPD were not being adequately immunized because of the lack of evidence that these infants are protected by the conjugate pneumococcal vaccine (11). This survey indicated that many infants who were immunized were not receiving the recommended booster dose in the second year of life. In the UK immunization schedule at this time, none of the other vaccines in the primary schedule were boosted.The immunogenicity of PCV7 when administered to preterm infants according to the then-current UK immunization schedule was examined and compared to the response of a cohort of term infants that was previously described. As many preterm infants were not routinely receiving their 12 -month booster, we also measured antibody levels at 12 months of age.     

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.