Immunogenicity and safety of an investigational AS02(v)-adjuvanted hepatitis B vaccine in patients with renal insufficiency who failed to respond or to maintain antibody levels after prior vaccination: results of two open, randomized, comparative trials

An investigational AS02_v-adjuvanted hepatitis B (HB-AS02) was compared with a licensed conventional recombinant hepatitis B vaccine (HBVAXPRO™; Sanofi Pasteur MSD, Lyon, France) in pre-dialysis, peritoneal dialysis and hemodialysis patients aged ≥18 years who had failed either to respond to prior vaccination with a conventional hepatitis B vaccine (Study A; n = 251) or to maintain protective antibody concentrations after prior hepatitis B vaccination (Study B; n = 181). These were open, randomized, comparative trials. Mean (range) age was 65.9 (31-92) and 64.6 (29-92) years in the two studies, respectively. In Study A, two doses of HB-AS02 given one month apart were found to be superior to two doses of the licensed vaccine in terms of seroprotection rate (76.9% versus 37.6%) and anti-HBs geometric mean antibody concentration (GMC; 139.3 versus 6.9 mIU/ml), with antibody concentrations ≥100 mIU/ml in 61.1% and 15.4% of subjects in the two groups, respectively. In Study B, one month after administration of a single booster dose, seroprotection rates were 89.0% in the HB-AS02 group and 90.8% in the licensed vaccine group, 81.3% and 60.9% of subjects had antibody concentrations ≥100 mIU/ml, and anti-HBs GMCs were 1726.8 and 189.5 mIU/ml. HB-AS02 was found to be more reactogenic than the licensed vaccine. In summary, the investigational HB-AS02 vaccine induced higher seroprotection rates and anti-HBs GMCs than a licensed conventional hepatitis B vaccine in uremic patients who had failed to respond or to maintain protective antibody titers after prior hepatitis B vaccination.     

Presence of immune memory and immunity to hepatitis B virus in adults after neonatal hepatitis B vaccination

Neonatal vaccination against hepatitis B virus (HBV) infection was launched in the 1980s in Qidong, China, where HBV and hepatocellular carcinoma were highly prevalent. Presence of immune memory and immunity against HBV in adults needs to be clarified. From a cohort of 806 who received plasma-derived Hep-B-Vax as neonates and were consecutively followed at ages 5, 10, and 20 years, 402 twenty-four-year-old adults were recruited for booster test. Among them 4 (1%) were found to be HBsAg(+), 27 (6.7%) were HBsAg(−)anti-HBc(+), 121 (30.2%) were HBsAg(−)anti-HBc(−)anti-HBs(+), and 252 (62.4%) were HBsAg(−)anti-HBc(−)anti-HBs(−). Of them, 141 subjects with HBsAg(−)anti-HBc(−) were boosted with 10-μg recombinant HBV vaccine on day-0 and 1-month. The conversion rates of anti-HBs ≥10 mIU/ml on D10-12 and 1-month post-booster were 71.4% and 87.3% respectively in the vaccinees who were anti-HBs(+) at age 5, higher than in those who were anti-HBs(−) at age 5, 57.5% and 80.0% respectively, but no statistically significant. After the second dose of booster, all subjects with anti-HBs(+) at age 5 had anti-HBs >500 mIU/ml. However, 6/40 subjects, with anti-HBs(−) at age 5, had anti-HBs <10 mIU/ml, geometric mean concentration was 3.6 (95% CI 2.0-7.7). Of the subjects received booster, 44 subjects were determined the presence of T cell immunity on D10-12, 41 had HBsAg-specific T cells detectable, including 7/10 subjects whose anti-HBs were <10 mIU/ml 10-12 days post-booster. Among 27 HBsAg(−)anti-HBc(+) subjects, 19 had detectable serum HBV-DNA, and an “a” epitope mutation was found in 1/5 HBV isolates. One subject who was anti-HBc(+) at age 20 converted into HBsAg(+) 4 years later. The adults received neonatal HBV vaccination had immune memory and immunity against HBV infection. However, 31.9% of neonatal HBV vaccinees who responded weakly at an early age might be susceptible to HBV infection after childhood.     

Antibody levels and immune memory 23 years after primary plasma-derived hepatitis B vaccination: results of a randomized placebo-controlled trial cohort from China where endemicity is high

The duration of protection of hepatitis B vaccine remains incompletely understood. To assess the long-term protection provided by a primary vaccine series, the current study again recruited all subjects of a previous randomized placebo-controlled trial cohort 23 years after vaccination. Two hundred and sixty-one healthy children aged 5-9 years living in a highly HBV-endemic country were enrolled in the primary trial and received three doses of plasma-derived vaccine or placebo. The primary placebo receivers who did not receive any immunization against hepatitis B were used as non-vaccinated controls in the current study. After eliminating the interference of an early booster dose and vaccines outside the study, 48.1% (39/81) vaccinees still maintained anti-HBs titers ≥10 mIU/mL at Year 23, higher than 34.7% (26/75) in non-vaccinated controls (P = 0.088). 75-100% of vaccinees with anti-HBs titer <10 mIU/mL at Year 23 in different sub-groups divided according to early immune backgrounds developed a rapid and robust antibody anamnestic response after a booster dose, highly significantly different from non-vaccinated controls who received the same dose of vaccine (7.5%, P < 0.01). No case of clinically significant HBV infection was found in the primary cohort during the whole 23 years, but 10 transient HBsAg seroconversions in the primary placebo group and one in the primary vaccine group were determined. Anti-HBc positive rate obviously tended to be lower in vaccinees compared with non-vaccinated controls at Year 23. These results suggest a persisting immune memory and certain protection for 23 years after primary vaccination in children living in highly HBV-endemic areas. Clinically insignificant infections, which cannot be avoided and may often occur in vaccinees, play a positive role in the maintaining of immunity to HBV. Booster doses should be unnecessary for more than 20 years after a full primary immunization in children (as catch-up vaccination) and, also likely, in newborns living in highly HBV-endemic areas.     

Comparison of long-term (10 years) immunogenicity of two- and three-dose regimens of a combined hepatitis A and B vaccine in adolescents

300 adolescents aged 12–15 years were randomised (1:1) into two groups to compare the long-term (10 years) immunogenicity profile of two doses of an Adult formulation [Group HAB_2D: 150; 0–6 months] vs. three doses of a Paediatric formulation [Group HAB_3D: 150; 0–1–6 months] of a combined hepatitis A and B (HAB) vaccine. At Year 10, anti-HAV seropositivity rate was 100% in both groups, while 85.9% and 85.1% subjects in the HAB_2D and HAB_3D groups, respectively, had anti-HBs antibody concentrations ≥10 mIU/mL. The anti-HAV antibody GMCs (HAB_2D: 429.3 mIU/mL; HAB_3D: 335.5 mIU/mL) and anti-HBs antibody GMCs (HAB_2D: 50.6 mIU/mL; HAB_3D: 60.1 mIU/mL) were similar in both groups. No vaccine-related serious adverse events were reported. Hence, with respect to long-term antibody persistence, the two-dose schedule of the combined HAB vaccine Adult formulation is an effective alternative to the conventional three-dose schedule of the Paediatric formulation in adolescents.     

Immune response to hepatitis B vaccine with high antigen content in non-responders after standard primary vaccination in Chinese adults

Context

Alternative schedules are needed to provide greater immunogenicity in adults who fail to respond to the standard hepatitis B (HB) vaccine regimen.

Objective

To evaluate the immunogenicity and safety of high antigen content HB vaccine formulations administered to non-responders after routine primary vaccination.

Design setting, and participants

This was a phase III, double-blind, controlled clinical trial in China. We enrolled healthy participants (16–60 years old) seronegative for HB surface (HBs) antigen after primary vaccination, who had HBs antibody (anti-HBs) titres <10 mIU/ml at 28 days following routine vaccination with licensed HB vaccine containing 10 μg of antigen. Participants were randomised (2:2:1) to receive three booster doses of HB vaccine formulations containing 60 μg, 30 μg or 10 μg of antigen per dose 28 days apart. Blood samples were obtained pre-vaccination and 28 days after each dose to assess immunogenicity. Reactogenicity and safety were evaluated up to 28 days after each vaccine dose.

Results

Seroconversion rates were ≥92.1% and ≥87.1% as from the second dose of the 60 μg and 30 μg HB vaccine formulations, respectively, with geometric mean concentrations (GMCs) of ≥286.0 mIU/ml and ≥164.0 mIU/ml. In the 10 μg HB vaccine group the seroconversion rates were ≥83.0% and the GMCs ≥110.1 mIU/ml as from the second vaccine dose. All HB vaccine formulations were well tolerated: 352/1091 (32.3%) participants reported at least one injection-site or systemic adverse reaction (145/434 [33.4%] from the 60 μg group; 138/435 [31.7%] from the 30 μg group and 69/222 [31.1%] from the 10 μg group). Most reactions were mild or moderate and resolved within 24 h. No serious adverse events were reported.

Conclusion

Booster vaccination with a three-dose schedule of a high antigen content HB vaccine formulation was immunogenic and well tolerated in healthy adults.

Clinicaltrials.gov identifier

NCT01203319.     

Vaccine induced Hepatitis A and B protection in children at risk for cystic fibrosis associated liver disease

Objectives

Hepatitis A (HAV) and Hepatitis B (HBV) infections can cause serious morbidity in patients with liver disease, including cystic fibrosis associated liver disease (CFALD). HAV and HBV vaccinations are recommended in CFALD, and maintenance of detectable antibody levels is also recommended with chronic liver disease. A better understanding of factors predicting low HAV and HBV antibodies may help physicians improve protection from these viruses in CFALD patients.

Methods

We examined HAV and HBV vaccine protection in children at risk for CFALD. Clinical and vaccine histories were reviewed, and HAV and HBV antibody titers measured. Those with no vaccination history or low HAV or HBV titers received primary or booster vaccinations, and responses were measured.

Results

Thirty-four of 308 children were at risk for CFALD per project criteria. Ten had previous HAV vaccination, of which 90% had positive anti-HAV antibodies. Thirty-three of 34 had previously received primary HBV vaccination (most in infancy), but only 12 (35%) had adequate anti-HBs levels (≥10 mIU/mL). Children with adequate anti-HBs levels were older at first HBV vaccine (median 2.3 vs. 0.1 years, p < 0.01), and at final HBV vaccine (median 4.0 vs. 0.8 years, p = 0.01). Fourteen of 19 (74%) responded to HBV boosters. Z-scores for BMI at HBV booster were significantly lower in booster non-responders (p = 0.04).

Conclusions

Children at increased risk of CFALD have inadequate HAV and HBV antibody levels, and HBV antibody protection can be enhanced through vaccine boosters. HBV antibody titers should be assessed in CFALD patients with a history of vaccination, particularly in those who received HBV vaccines in infancy or who are malnourished.     

Differences in avidity of IgG antibodies to pertussis toxin after acellular pertussis booster vaccination and natural infection

Background

Pertussis toxin (PT) is a specific virulence factor of Bordetella pertussis and it is included in all acellular pertussis vaccines (aP). Although immunity after infection seems to persist longer than that after vaccination, the exact mechanism(s) is not known. Primary aim of this study was to develop an ELISA method for measuring avidity index (AI) of IgG-anti-PT antibodies and to compare antibody responses after booster vaccination and infection. Secondary aim was to evaluate if the AI-ELISA has potential in the serodiagnosis of pertussis.

Material

Serum samples from a total of 409 subjects were included in the study. Paired sera were taken from 97 adolescents who received booster vaccine ten years ago (dTpa-004) and from 80 young adults who received a second booster dose ten years after the previous booster vaccine (dTpa-040). Thirty-two paired sera from culture-confirmed pertussis patients, 161 single sera from serologically diagnosed patients and 39 single sera from healthy controls were included. AI of IgG-anti-PT antibodies were determined with newly developed ELISA using diethylamine (DEA) as a bond breaking agent. The IgG-anti-PT antibodies were measured by standardized ELISA.

Results

A significant increase was found in antibody concentrations and AI between PRE and one month POST vaccination ten years ago [GMC for antibody: 7.9 IU/ml vs. 98.3 IU/ml (p = 0.0001); for AI: 40.4% vs. 56.1% (p = 0.0001)]. Similar result was observed after the second booster dose [GMC for antibody: 9.2 IU/ml vs. 92.4 IU/ml (p = 0.0001); for AI: 36.1% vs. 59.5% (p = 0.0001)] and between the first and second sera of culture-confirmed patients [GMC for antibody: 6.9 IU/ml vs. 285.1 IU/ml (p = 0.0001); for AI: 40.5% vs. 68.4% (p = 0.0001)]. Healthy controls showed lower levels of both antibodies and AI.

Conclusions

Our results suggest that there may be difference in quality and quantity of antibodies to PT after vaccination and after infection. Furthermore, AI could be a help for vaccine studies.     

Prevalence of protective level of hepatitis B antibody 3 years after revaccination in HIV-infected children on antiretroviral therapy

After responding to highly active antiretroviral therapy (HAART), HIV-infected children had a good response to hepatitis B immunization. However, there are limited data on the durability of antibody to hepatitis B surface antigen (anti-HBs) in these children. The primary objective of this study is to determine the prevalence of protective anti-HBs level 3 years after a 3-dose HBV revaccination among HIV-infected children with immune recovery (CD4 cell ≥15%) while on HAART. The secondary objective is to assess immunologic memory among children who had waning of anti-HBs. An anti-HBs level of ≥10 mIU/mL was defined as a protective antibody level. Sixty-nine HIV-infected children who had history of a 3-dose HBV revaccination while receiving HAART were enrolled. The mean (SD) of CD4 cell and duration of HAART at time of revaccination was 27.2% (6.7) and 5.9 years (0.4), respectively. The proportion of children with protective anti-HBs level 3 years after the revaccination was 71.0% [95% CI, 58.8-81.3]. The geometric mean titer was 114(SD 5) IU/mL. By multivariate logistic analysis, the predictors for protective anti-HBs level 3 years after revaccination were CD4 cell count ≥500 cells/mm³ at the time of vaccination (p = 0.04) and anti-HBs level ≥ 100 IU/mL at 1 month after completion of the 3-dose vaccination (p < 0.001). Anamnestic response after one booster dose was demonstrated among 14 of 17 children who had waning protective anti-HBs level (82.4% [95% CI, 62.2-102.6]). Our findings support the recommendation of giving a 3-dose HBV vaccination to HIV-infected children with immune recovery while receiving HAART.     

Assessment of long-term efficacy of hepatitis B vaccine

In a healthy cohort of 462 subjects in which hepatitis B vaccine was administered between 1990 and 1992 a follow-up study was carried out to determine the duration of protection. Individuals with antibody against the hepatitis B virus surface antigen (anti-HBs) titer lower than 100 mIU/ml were administered a booster dose and antibodies determined 30 days later. The proportion of protection 6.5 years after vaccination was 85% (95% CI: 82–88). Only nine vaccinees seroconverted to anti-HBc positivity without becoming carrier or ill. In 125 subjects in which a booster dose was administered a significant increase in geometric mean of anti-HBs titer was observed (609 mIU/ml) as compared to late (13 mIU/ml) and early post-vaccination antibody levels (256 mIU/ml, Wilcoxon's test, p < 0.001) suggesting the existence of an anamnestic response. We conclude that in immunocompetent population it is not necessary to administer a booster dose 6.5 years after hepatitis B vaccination.     

Immunogenicity of hepatitis B vaccine among hemodialysis patients: effect of revaccination of non-responders and duration of protection

Background

Hepatitis B vaccination is recommended for patients on hemodialysis, however, seroprotection after a primary vaccine series is suboptimum. Limited data are available on the effect of revaccination of non-responders and on persistence of immunity in this population.

Methods

Hepatitis B vaccine (40 μg/dose) was given to 77 susceptible patients on hemodialysis (0, 1, and 6 month schedule). Levels of hepatitis B surface antibody (anti-HBs) were tested ≥28 days after the third dose was administered, and non-responders revaccinated with an additional 3-dose series. Vaccine responders (anti-HBs ≥10 mIU/mL) were re-tested every 6 months and booster doses given as needed. Kaplan-Meier survival curve was used to estimate the probability of maintaining protective antibody level. Cox-proportional hazards models were used to assess the association between time to loss of protective antibody levels and certain explanatory variables.

Results

Overall primary vaccine-induced response was 79.2% (95% CI 68.2%, 87.3%), including 49/77 (63.6%; 95% CI 51.8%, 74.7%) patients who received the initial primary hepatitis B vaccine series and 12/21 (57.1%; 95% CI 34.4%, 77.4%) non-responders who were revaccinated with an additional series. Among weak responders (anti-HBs level 10.0-99.9 mIU/mL), protective antibody levels persisted in 44% for 12 months post-vaccination; whereas among strong responders (anti-HBs level ≥100 mIU/mL), protective antibody levels persisted in 92% for 12 months, and 68% for 24 months post-vaccination. A weak post-vaccination response increased the risk of losing protective antibody levels (adjusted hazard ratio, 9.7; 95% confidence interval, 3.5-28.5; p < 0.0001).

Conclusion

Revaccinating patients undergoing hemodialysis who do not respond to a primary vaccine series substantially increases the pool of protected patients. The threshold for defining hepatitis B vaccine-induced immunity should be revisited in this patient population to maximize the duration of protection.     

Long-term (5-year) antibody persistence following two- and three-dose regimens of a combined hepatitis A and B vaccine in children aged 1–11 years

This study compared the long-term persistence of anti-hepatitis A (anti-HAV) and B (anti-HBs) antibodies, 5 years after vaccination of subjects aged 1–11 years with a combined hepatitis A and B vaccine either in a two-dose (0, 6 months, Adult formulation) or a three-dose (0, 1, 6 months, Paediatric formulation) schedule. At the end of the 5 years, all subjects (100%) in both groups continued to have anti-HAV antibodies ≥15 mIU/mL, while 94–97% of subjects in both groups had anti-HBs antibody concentrations ≥10 mIU/mL. Subjects with anti-HBs antibody concentration ≤10 mIU/mL were administered a challenge dose of hepatitis B vaccine. All subjects mounted a vigorous immune response to the challenge indicating the presence of immunological memory to HBV.     

Randomized study of intradermal compared to intramuscular hepatitis B vaccination in HIV-infected children without severe immunosuppression

HIV infected individuals have poorer response to hepatitis B vaccine (HBV) compared to normal host. Intradermal administration (ID) facilitates the exposure of antigen to antigen-presenting cells compared to intramuscular administration (IM).HIV-infected children aged 1-18 years with CD4% ≥ 15% or 200 cells/mm³ who had negative HBs Ag, antiHBs, and antiHBc were randomized to receive 3-dose of HBV via ID (2 μg/dose) or IM (10 μg/dose) route at months 0, 2, and 6. AntiHBs titers were measured at months 2, 6 and 7 after first HBV. AntiHBs ≥ 10 mIU/mL was considered protective and AntiHBs > 100 mIU/mL was considered good response.Participants included 41 in ID and 39 in IM arms. 64% had completed 3-doses HBV during infancy. The mean (SD) of age, nadir CD4% and current CD4% were 12 (3.3) years, 10.6 (7.9)% and 28 (8.0)% respectively. 91% were on HAART and 84% had undetectable HIV-RNA.Proportion of children with protective antiHBs in ID vs. IM group were 19.5% vs. 25.6% at month 2, 56.1% vs. 76.9% at month 6, and 90.2% vs. 92.3% at month 7 (NS, all). The geometric mean (95% confidence interval) of antiHBs titer in ID vs. IM group were 112.5 (34.4-367.6) vs. 141.2 (49.4-404.1) mIU/mL at month 2 (p = 0.74), 70.4 (39.8-124.4) vs. 132.1 (79.4-219.8) mIU/mL at month 6 (p = 0.10), and 157.0 (103.0-239.3) vs. 458.9 (324.0-647.0) mIU/mL at month 7 (p < 0.001). However, only 56.1% of the ID arm had good response to HBV compared to 82.1% in the IM arm (p = 0.01). The predictors for being a good responder to HBV were IM administration [OR 4.0, 95%CI 1.4-11.8, p = 0.012] and body weight <35 kg at baseline [OR 3.8, 95%CI 1.3-10.8, p = 0.013]. No adverse events grade 3/4 occurred.In conclusion, HIV-infected children without severe immune suppression, both ID and IM routes of HBV resulted in similar rates of protective antibody titers. However, high antibody titers to HBV were more common with IM; therefore, IM administration is preferred.     

Long-term immunogenicity of hepatitis B vaccination in a cohort of Italian healthy adolescents

In 1992, 620 adolescents were vaccinated against hepatitis B. Anti-HBs concentrations were measured in 480 (77.4%) adolescents 1 month after completion of the primary course of vaccination. To assess the persistence of anti-HBs, 347 and 228 of such vaccinees were retested for anti-HBs in 1999 and for anti-HBs and anti-HBc in 2003. More than 10 years after vaccination, individuals with anti-HBs >or=10 mIU/ml were considered protected while those with antibody <10 mIU/ml were given a booster dose and retested 2 weeks later. Check performed in 2003 showed that 208/228 (91.2%) vaccinees retained protective concentrations of anti-HBs. All vaccinees were anti-HBc negative. 11 of the 12 (91.7%) individuals who were given a booster dose of vaccine showed a vigorous anamnestic response while the remaining one showed a weak response (10.6 mIU/ml). These data suggests that hepatitis B vaccination can confer long-term immunity and that immunological memory can outlast the loss of antibody. Hence, the use of routine booster doses of vaccine does not appear necessary to maintain long-term protection in successfully vaccinated immunocompetent individuals.     

Impact of maternal carrier status on immunologic markers for protection after hepatitis B vaccination in infancy: A meta-analysis

Better protection against hepatitis B infection in offspring of carrier mothers has been postulated because of a booster effect by close maternal contact. Empirical evidence, however, is inconclusive. Immunologic markers for protection against hepatitis B are anti-HBs≥10mIU/ml or response to booster in case anti-HBs had fallen below 10mIU/ml. The objective of this paper was to asses whether immunologic markers suggest a higher protection after hepatitis B vaccination in offspring of carrier mothers. A systematic review was performed in order to identify all studies in offspring of carrier and non-carrier mothers reporting the proportions of individuals with anti-HBs≥10mIU/ml after infant hepatitis B vaccination with a presently recommended dose in children aged 5years or older or response to a booster dose in case anti-HBs was below 10mIU/ml. Associations between carrier status and the proportions of anti-HBs≥10mIU/ml or booster response were analysed by random effects models with adjustment for age and potential confounders. We identified 19 studies providing proportions of anti-HBs≥10mIU/ml with explicit information regarding the maternal carrier status. These studies reported 3245 children of carrier mothers aged up to 20years and 4602 children of non-carrier mothers aged up to 14years. Antibody titres≥10mIU/ml were detected in 75.8% of children of carrier and 63.6% of non-carrier mothers. A random effects model with adjustment for confounding yielded an odds ratio of 2.43 (95% CI 1.24-4.75) suggesting a markedly higher probability of anti-HBs≥10mIU/ml in offspring of carrier compared to non-carrier mothers. The distribution of proportions of individuals with post booster increase of anti-HBs titres≥10mIU/ml stratified by age at booster (≤10years and >10years) showed no differences between offspring of carrier and non carrier mothers up to the age of 10years and only marginal differences thereafter. In conclusion the proportions of anti-HBs≥10mIU/ml were clearly higher in offspring of carrier mothers years after infant vaccination but there appeared to be no clinically relevant difference in response to booster. It is unclear to which extent higher proportions of breakthrough infections contribute to the higher proportions of protective antibody titres in offspring of carrier mothers.     

The induction of breast milk pertussis specific antibodies following gestational tetanus–diphtheria–acellular pertussis vaccination

Background

Center for Disease Control and Prevention recommends vaccination of pregnant women with tetanus–diphtheria–acellular pertussis (Tdap).

Aim

To measure pertussis specific antibodies, total protein and their ratio in breast milk following gestational Tdap vaccination.

Methods

Women who received Tdap after the 20th week of pregnancy were recruited and unvaccinated women served as controls. Breast milk total protein, immunoglobulin A (IgA) to pertussis toxin (PT), filamentous hemagglutinin (FHA) and immunoglobulin G (IgG) to PT, FHA and pertactin (PRN) were measured. To overcome the dilution that occurs in the transition from colostrum to mature breast milk, we calculated pertussis specific antibody to total protein ratio.

Results

Pertussis specific IgA was the predominant pertussis immunoglobulin in the colostrum of Tdap vaccinated women with the geometric mean concentrations (GMCs) of IgA to FHA higher than for IgA to PT, 24.12 ELISA units/milliliter (EU/mL) vs. 8.18 EU/mL, respectively, p < 0.004. There were differences between the vaccinated women and controls in the GMCs of IgA to FHA and IgG to PRN in the colostrum, 24.12 EU/mL vs. 6.52 EU/mL, p = 0.01 and 2.46 EU/mL vs. <0.6 EU/mL, p = 0.03, respectively. The GMCs of total protein showed significant decline over 8 weeks in the vaccinated women and controls, p < 0.004. Among vaccinated women, there was significant decline in the GMCs of IgA to PT and FHA over 8 weeks, p < 0.001. The geometric mean ratio of IgA to FHA to total protein also declined significantly over 8 weeks in the vaccinated women, p < 0.01, demonstrating a true decrease, however, pertussis IgA was measurable at 8 weeks.

Conclusions

Select colostrum pertussis antibody levels were significantly higher among women vaccinated with Tdap during pregnancy compared with unvaccinated women. Among vaccinated women, maximal levels of pertussis specific IgA were in the colostrum but still detected at 8 weeks. Lactation may augment infant's protection against pertussis.     

Hepatitis B vaccine response among infants born to hepatitis B surface antigen-positive women

Purpose

Annually, an estimated 25,000 infants are born to hepatitis B surface antigen (HBsAg)-positive women in the United States. Hepatitis B (HepB) vaccine and hepatitis B immune globulin (HBIG) are recommended at birth, followed by completion of vaccine series and post-vaccination serologic testing (PVST). In a large cohort of infants born to HBsAg-positive women, factors influencing vaccine response were evaluated.

Methods

Data were from HBsAg-negative infants born to HBsAg-positive women in the Enhanced Perinatal Hepatitis B Prevention Program (EPHBPP) from 2008 to 2013. Vaccine non-responders were defined as infants with antibody to hepatitis B surface antigen (anti-HBs) <10 mIU/mL at PVST after receiving ≥3 vaccine doses. Multivariable analyses modeled statistically significant predictor variables associated with non-response.

Results

A total of 17,951 maternal-infant pairs were enrolled; 8654 HBsAg-negative infants born to HBsAg-positive mothers received ≥3 doses of vaccine with anti-HBs results. 8199 (94.7%) infants responded to a primary HepB series; 199 (94.8%) to a second series. Factors associated with anti-HBs <10 mIU/mL included gestational age <37 weeks, vaccine birth dose >12 h after birth, timing of final vaccine dose <6 months after birth, receipt of 3 vs. 4 vaccine doses, and PVST interval >6 months from final vaccine dose in bivariate analysis. PVST interval >6 months from final vaccine dose (OR = 2.7, CI = 2.0, 3.6) was significantly associated with anti-HBs <10 mIU/mL; the proportion increased from 2% at 1–2 months to 21.6% at 15–16 months after the final dose. Receipt of a 4th dose improved the response rate (OR = 0.5, CI = 0.3, 0.8).

Conclusions

Ninety-five percent of a large cohort of uninfected infants born to HBsAg-positive mothers in the United States responded to primary HepB vaccine series. The proportion of infants with anti-HBs <10 mIU/mL increased with longer interval between the final vaccine dose and PVST. Optimal timing of PVST is within 1–2 months of final vaccine dose to avoid unnecessary revaccination.     

The immunogenicity and impact on nasopharyngeal carriage of fewer doses of conjugate pneumococcal vaccine immunization schedule

The immunogenicity and impact on carriage of fewer doses of pneumococcal conjugate vaccine (PCV7) followed by booster with pneumococcal polysaccharide vaccine (PPV) were investigated. 684 infants were assigned randomly to one of the three groups that received one (A), two (B) or three (C) doses of PCV7 between 2 and 4 months of age, plus PPV at 10 months. Following primary vaccination protective antibody titers of >0.35 μg/ml against the PCV7 serotypes combined increased significantly with the number of PCV7 doses, 44% vs. 77% vs. 94% (p < 0.001), and correlated positively with the opsonophagocytic indices, but negatively with nasopharyngeal carriage of pneumococcus. The differences in antibody responses and pneumococcal carriage between the groups diminished following booster with PPV, implying that administration of one or two doses of PCV7, with a booster dose of PPV might lower the cost of protection against IPD in young children in resource poor countries.     

抗-HBs衰减青少年乙肝疫苗加强免疫效果研究

目的研究乙肝疫苗(Hepatitis B Vaccine,HepB)基础免疫后12～15年乙肝病毒表面抗原抗体(抗-HBs)衰减者加强免疫前后抗体水平间的关系,比较不同剂次的加强免疫效果。方法选择婴儿期完成HepB基础免疫的1993—1997年出生的儿童,采集静脉血,使用化学发光法检测后,HBsAg及抗-HBc阴性而抗-HBs降至保护性水平(10mIU/ml)以下作为研究对象。按抗-HBs滴度水平分为3组:Ⅰ组(﹤0.1 mIU/ml)、Ⅱ组(0.1～1 mIU/ml)和Ⅲ组(﹥1 mIU/ml);按0、1、6免疫程序加强免疫3剂10μg的重组乙肝疫苗(汉逊酵母)(HepB-HPY),分别于免疫1剂和3剂后1个月采集静脉血,检测抗-HBs。结果 453名研究对象加强免疫1剂后各组抗-HBs阳转率分别为67.96%、85.61%和97.60%,抗体滴度分布差异有统计学意义(χ2=132.88,P﹤0.05),几何平均浓度(GMC)分别为37.31、152.77和1310.27 mIU/ml(F=86.11,P﹤0.05);加强免疫3剂后各组抗-HBs阳转率分别为99.00%、99.21%和99.49%(Fisher确切概率法,P﹤0.05),GMC分别为1714.67、1502.32和3383.68 mIU/ml(F=16.59,P﹤0.05)。全程采血的425名儿童在免疫1剂和3剂后抗体阳转率分别为87.76%和99.29%(χ2=46.68,P﹤0.05)。结论对于完成HepB基础免疫后抗体衰减至10 mIU/ml以下的12～15岁儿童有必要进行加强免疫,加强免疫前抗体滴度较高者加强免疫效果较好;加强免疫3剂比1剂效果好。     

Evaluation of the response to a booster dose of hepatitis B vaccine in previously immunized healthcare workers.

INTRODUCTION: Hepatitis B vaccination is recommended for all healthcare workers (HCW) at risk of exposure to infectious body fluids. However, the absolute duration of protection from immunization is unknown. The purpose of this randomized comparison trial was to determine how previously immunized HCW respond to different booster doses of hepatitis B vaccine. METHOD: Adult HCW (n=59) were classified by level of hepatitis B surface antigen (anti-HBs), either <10 milli-International Units per milliliter (mIU/ml) or 10-50 mIU/ml. Participants were then randomized to receive a 2.5 or 10 microg dose of hepatitis B vaccine. Evaluation of anti-HBs levels were conducted 10 to 14 days, one month and one year postbooster. RESULTS AND DISCUSSION: All participants responded to the booster dose with increased anti-HBs levels. At 14 days, mean anti-HBs levels were significantly higher for those with higher levels at baseline (P=0.004) and those receiving the 10 microg dose (P=0.016). At one month, those with higher anti-HBs levels at baseline and those receiving the 10 microg dose were significantly higher (P<0.01 for both). At one year, the increase for the higher dose was no longer statistically significant when examined by itself (P=0.081); statistical significance (P=0.021) was achieved after adjusting for anti-HBs level at baseline. For all participants, the geometric mean anti-HBs level was 2618 mIU/ml at 14 days, 2175 mIU/ml at one month and 88.9 mIU/ml at one year. At all time points the increase in anti-HBs levels represented an increase over the geometric mean baseline level of anti-HBs (7.4 mIU/ml). Hepatitis B immunized adults responded to a booster dose of hepatitis B vaccine from 3 to 13 yr postvaccination series. Data support current recommendations that immunized HCW do not require periodic antibody testing or vaccine boosters.     

Antibody persistence six years after two doses of combined hepatitis A and B vaccine

Persistent immunity to hepatitis A and hepatitis B antibodies six years after vaccination of adolescents (aged 12–15 years) with a combined hepatitis A and B (HAB) vaccine following a 0, 6 month or a 0, 12 month schedule was assessed. Yearly (Year-2–6) serum samples were tested for anti-HAV and anti-HBs using EIA. Subjects with anti-HBs concentrations <10 mIU/mL (14/23) at Year-5 or Year-6, received an additional HBV vaccine dose ∼12 months after Year-6. Blood samples were collected pre-booster and 1 month post-booster to assess booster response. 240 subjects were vaccinated in the study; at Year-6, data were available from 88 subjects. At that time 84.8% (39/46; 0, 6 month) and 92.9% (39/42; 0, 12 month) of subjects had anti-HBs concentrations ≥10 mIU/mL. All but one of the 14 boosted subjects responded to the additional HBV vaccine dose with anti-HBs concentrations ≥100 mIU/mL. All seroconverted subjects who returned at Year-6 were seropositive for anti-HAV. Simplification, reduced number of doses and similar long-term persistence of immunity make the 0, 6 month and 0, 12 month schedule preferable for immunization against HAV/HBV in this population.