Doses Of HBV Vaccine Research Articles

Immune response to second vaccination series of hepatitis B virus among booster dose non-responders

ObjectiveTo evaluate the response to second vaccination series among post-booster sero-negative children who had previously received compulsory HBV vaccination. Subjects and methodsAfter given a booster dose to 1070 children, 103 of them failed to generate anamnestic response (anti-HBs <10IU/L). Only 91/103 children received additional two doses of recombinant HBV vaccine (i.e. 2nd vaccination series) after 1 and 6 months post-booster. Blood sample was withdrawn aseptically one month later for quantitative assessment of anti-HBs to detect development of protective immune response (≥10IU/L). Immunological vaccination failure was assigned to children who did not develop protective immune response after 2nd vaccination series. ResultsProtective immune response was detected among 84/91 children (92.3%). While 7/91 (7.7%) whose age were ≥10 years did not respond and had post-booster undetectable anti-HBs. About 80% of children with post-booster detectable anti-HBs showed significant protective immune response (anti-HBs ≥100IU/L) and higher GMT (299.1±3.6IU/L) compared to those with undetectable 60% and 106.2±12.9IU/L respectively (P<0.05). No significant difference was detected as regards gender or residence, P>0.05. All children with history of rheumatic fever (7 children) or diabetes mellitus (1 child) developed immune response after 2nd vaccination series. ConclusionA booster dose of HB vaccine may be unable to induce sufficient immunological response in children who had undetectable anti-HBs titers. Revaccination for non-responders is an important procedure to increase HBV protection rate.

Seroprevalence of anti-HBs antibodies at young adulthood, before and after a booster vaccine dose, among medical personnel vaccinated in infancy

BackgroundQuestions remain regarding the long-term protection provided by childhood HBV vaccination. The goals of this study were to assess HBV seroprevalence among medical personnel purportedly vaccinated in infancy; to investigate the immune response after a booster dose given in young adulthood; and to identify predictors of non-responders. MethodsBetween 2011 and 2013 we studied Israeli male military recruits purportedly vaccinated in infancy. All subjects were born after January 1st 1992 and were undergoing medic training. We collected personal data and blood samples at baseline, and administered a dose of HBV vaccine. Subjects were retested one month later and received a second dose. A third blood draw was conducted one month after the second dose. Data collected at baseline were used as predictor variables of seropositivity (anti-HBs≥10mIU/ml). Results617 subjects were available for baseline analysis and 539 for paired observations at one month. Baseline seropositivity was 33.7%. Subjects who received post-infancy vaccine doses had a seropositivity rate double that of those denying additional doses (RR 2.22, 95% CI 1.55–3.18). One month after the first booster dose, the overall cumulative population seropositivity reached 87.7%. One month after the second vaccine dose, population seropositivity was 97.9%. Heavy smokers were 5 times less likely to demonstrate detectable antibodies after a single booster dose (OR 0.196, 95% CI 0.060–0.641, P=0.007). ConclusionsThis population-based study is important for informing public health vaccination policy. Our results strongly indicate that among cohorts vaccinated in infancy, two doses in adulthood will provide maximal protective antibody levels, while one dose will provide sufficient population protection.

O011 : A nationwide survey of hepatitis E virus infection in liver transplant recipients in Japan

Results: Infrequent intrahepatic total HBVDNA (2/22, 9.1%) and cccDNA (1/22, 4.5%) were detected in biopsies; HBsAg and HBcAg IHC staining was negative. HBV-specific T cell responses were similar between “anti-HBc alone” individuals and HBV resolvers (Figure 1). Circulating HBV-memory B cell responses were detected in all “anti-HBc alone” individuals, consistent with an HBsAgspecific memory pool. After one HBV vaccine dose, increased antiHBs antibody levels were observed, accompanied by an expansion of HBsAg-specific memory B cells (P =0.0226) (Figure 2). Conclusions: “Anti-HBc alone” individuals showed HBV-specific T cell and memory B cell responses typical of previous viral exposure and protective memory, suggesting a resolved infection.

P0578 : HBsAg negative anti-HBc positive serology increases the risk of HCC in chronic hepatitis patients: A meta-analysis

Background and Aims: There are concerns with regards to the efficacy of combination (DTaP-IPV-HiB-HBV) vaccine, especially in infants with high risk of vertical transmission, and there has been no study comparing the vaccine efficacy in those receiving three doses of monovalent HBV vaccine versus two doses monovalent plus one dose of combination vaccine in infants of chronic HBVinfected mothers. The aim of this study is to examine the anti-HBs antibody levels of both vaccine regimens in a cohort of these highrisk infants. Methods: An observational cohort of term neonates was recruited from June 2009 to June 2014 from multiple primary to tertiary centres in Singapore. Anti-HBs antibody levels were measured at 9 months of age. Vaccine regimen administered were based on the individual institutions’ practice. Results: All term neonates received monovalent hepatitis B vaccine with hepatitis B immunoglobulin at birth with a repeat dose of monovalent hepatitis B vaccine at 1 month. They received either monovalent (n = 111) or combination vaccine (n =95) at 6 months. Baseline maternal age (31.3 year vs 32.9 years), hepatitis B e-antigen positivity (24% vs 28%, p = 0.78) and birth characteristics, including gestational age (38 weeks versus 38weeks, p = 0.34), birth weight (3.13 kg vs 3.16 kg, p = 0.62) were similar between groups. The mean anti-HBs antibody were both not statistically different (478 IU/L vs 469 IU/L, p = 0.88). Vaccine failure rate (anti-HBs antibody <10 IU/L) was 4.5% vs 4.7% (p =1.00). Vertical transmission rate (HBsAg or HBVDNA positive) was 1.8% vs 2.3% (p =0.78). Conclusions: For term neonates delivered by chronic HBVinfected mothers, both 3-dose monovalent and combination vaccine regimen showed similar vaccine efficacy, with no increased risk of vertical transmission.

Occult hepatitis B virus infection in children born to HBsAg-positive mothers after neonatal passive-active immunoprophylaxis.

Occult hepatitis B virus infection (OBI) is a well-recognized clinical entity characterized by the detection of HBV DNA in serum and/or liver in the absence of detectable HBsAg. Diagnosis of OBI requires a sensitive HBV DNA assay. We aimed at determining the frequency of OBI in infants, born to HBsAg-positive mothers, who received immunoprophylaxis at birth. Sixty-four infants and children, born to HBsAg-positive mothers, who received hepatitis B immunoglobulin and HBV vaccine within 48 h after birth, were tested for HBV serological profile and HBV DNA by real-time PCR at least 1 month after last dose of HBV vaccine and not before 6 months of age. The median age of the studied infants and children was 8 months, ranging from 6 to 132 months; 54.7 % were females. HBV DNA was detected in 2 infants. One case had OBI; she was negative for HBsAg, anti-HBc total, HBeAg and was positive for anti-HBs (titer 267 mIU/mL) with low level of viremia (HBV DNA 1.13 x 10(3) IU/mL). Another infant showed immunoprophylaxis failure with positive HBsAg, anti-HBc total, HBeAg, negative anti-HBe and anti-HBs; HBV viral load was 1.7 × 10(8) IU/mL. Both mothers were HBsAg and HBeAg-positive. OBI may occur in infants born to HBsAg-positive mothers despite the receipt of immunoprophylaxis. OBI was detected in a low frequency in the present study. Anti-HBs positivity does not exclude OBI.

Does Nigeria need the birth dose of the hepatitis B vaccine?

The control of hepatitis B infection involves several strategies of which the most effective is vaccination. Schedules which include a birth dose (which can prevent vertical transmission when administered within 24 hours of birth) are recommended for use in countries with a high rate of vertical transmission. Nigeria is highly endemic for hepatitis B infection. Nigeria had hitherto utilized the monovalent HBV vaccine in the three dose schedule that includes a birth dose, the recent introduction of an HBV containing pentavalent vaccine (which cannot be administered at birth) calls to question whether there should be continued use of the birth dose of HBV (using the monovalent vaccine) in addition to three doses of the pentavalent vaccine given subsequently. This is given the fact that most infections in Nigeria are reportedly acquired in childhood through horizontal rather than vertical transmission. There is also the question of cost- effectiveness of the four dose schedule compared to the three dose schedule in the setting of Nigeria’s hepatitis B epidemiologic profile.A review of the available evidence indicates that a significant proportion of Nigerian women of child bearing age and pregnant women are seropositive for HBsAg and HBeAg. Maternal to child transmission rates of HBsAg of 47-53.3% have been documented while a significant proportion of newborns were noted to have serological markers for HBV infection before receiving their first immunization. These data indicate that there is a significant potential for vertical transmission of HBV in Nigerian infants providing a compelling reason for the continued use of the birth dose of the HBV vaccine. Cost-effectiveness was not examined in this review.There are, however, challenges to the universal delivery of the birth dose in a timely fashion. Encouraging institutional delivery, routine screening of pregnant women (with the administration of HBV within 24 hours of birth to infants of seropositive mothers), retraining of health care workers on ensuring the timely receipt of the birth dose of HBV vaccine and health education of mothers and the community on the need for immunization within 24 hours of birth are suggested strategies to improve the timely uptake of the birth dose of HBVKeywords: Birth dose, Hepatitis Bvaccine, Nigeria, Infants

Seroprevalence of hepatitis B and immune response to hepatitis B vaccination in Chinese college students mainly from the rural areas of western China and born before HBV vaccination integrated into expanded program of immunization

The prevalence of hepatitis B surface antigen (HBsAg) in a population aged 15 y or older was high in China, but an immunization strategy for this population was unavailable. We investigated the seroprevalence of hepatitis B and immune response to HBV vaccine in Chinese college students (n = 2040 participants), 11.1%, 80.8%, and 8.1% had confirmed, unknown and no HBV vaccination history, respectively. The seropositive rates for HBsAg, anti-HBs sole and anti-HBs plus anti-HBc were 12.6%, 25.7%, and 30.1%, respectively. The HBsAg seropositive rate was significantly lower in participants with confirmed HBV vaccination history than in those with unknown or no vaccination history (5.3%, 13.6%, and 12.6%, respectively, P = 0.0019). The anti-HBs alone seropositive rate was significantly higher in participants with confirmed HBV vaccination history than in those with unknown or no vaccination history (37.6%, 25.3%, and 13.8%, respectively, P < 0.0001). Participants negative for HBsAg, anti-HBs, and anti-HBc at baseline (n = 600) were given three doses of recombinant HBV vaccine (GlaxoSmithKline) at month 0, 1, and 6. Robust immune response was elicited after two and three doses (seroprotective rate: 91.9% and 99.0%, respectively, and geometric mean concentration [GMC]: 95.8 and 742.6 IU/L, respectively). Fourteen months after the third dose, the anti-HBs seroprotective rate of the group remained more than 97%. The seroprotective rates and GMCs did not differ significantly by vaccination history. This study suggested that three doses of 20 μg HBV vaccine were needed for college students negative for HBsAg, anti-HBs, and anti-HBc to ensure high seroprotective rates and concentrations.

Observational Study of Vaccine Efficacy 24 Years after the Start of Hepatitis B Vaccination in Two Gambian Villages: No Need for a Booster Dose

ObjectivesTo determine the duration of protection from hepatitis B vaccine given in infancy and early childhood and asses risk factors for HBV infection and chronic infection.MethodsIn 1984 infant HBV vaccination was started in two Gambian villages. Cross sectional serological surveys have been undertaken every 4 years to determine vaccine efficacy. In the current survey 84.6% of 1508 eligible participants aged 1–28 years were tested. A spouse study was conducted in females (aged 14 years and above) and their male partners.ResultsVaccine efficacy against chronic infection with hepatitis B virus was 95.1% (95% confidence interval 91.5% to 97.1%), which did not vary significantly between age groups or village. Efficacy against infection was 85.4% (82.7% to 87.7%), falling significantly with age. Concentrations of hepatitis B antibody fell exponentially with age varying according to peak response: 20 years after vaccination only 17.8% (95% CI 10.1–25.6) of persons with a low peak response (10–99 mIU/ml) had detectable HBs antibody compared to 27% (21.9% to 32.2%) of those with a high peak response (>999 mIU/ml). Time since vaccination and a low peak response were the strongest risk factors for HBV infections; males were more susceptible, marriage was not a significant risk for females. Hepatitis B DNA was not detected after infection, which tested soley core antibody positive. An undetectable peak antibody response of <10 mIU/ml and a mother who was hepatitis B e antigen positive were powerful risk factors for chronic infection.ConclusionsAdolescents and young adults vaccinated in infancy are at increased risk of hepatitis B infection, but not chronic infection. Married women were not at increased risk. There is no compelling evidence for the use of a booster dose of HBV vaccine in The Gambia.

The Hepatitis B Vaccine and Celiac Disease: More Lights Than Shadows?

Dear Editor, Actually, in literature, it is known that HLA-DQ2 haplotype is over-represented in celiac population and since both HBsAg protein fragments and gliadin peptides bind to HLA-DQ2 molecules; their competition may favors a defective antibody response against the recombinant HBsAg vaccine in active celiac disease (1). On the other hand, some studies demonstrate that in celiac individuals, the gluten intake at the time of vaccination influences the vaccine-induced immune response (2). All these hypotheses are still argument of debate because the non-responsiveness of celiac patients to the HBV vaccine remains a significant public health problem, although there is no convinced evidence that patients with viral hepatitis B show an increased risk of celiac disease (3). It would be important to assess the possible vaccination strategy in order to reduce this potential “healthy-reservoir” of infection. Regarding to this, new vaccination strategies for celiac patients were proposed in literature: the first one was the use of booster doses of HBV vaccine by intra-muscular route (IM), using higher doses or a higher number of injections after a gluten free diet; the second was the performance of vaccine boosters by intra-dermal route (ID) (4). The rational of the second strategy is that as opposed to intramuscular vaccination (IM), which relies on a T-cell mediated response, the vaccine directly introduced into the skin activates a dendritic-cell-mediated immune response, using a lower dose of antigen (5). The comparison of both routes suggests that both ID and IM routes are effective options to administer a booster dose of HBV vaccine in celiac patients although the ID route seems to result in a higher percentage of patients with an anti-HBs titer > 1000 IU/L (6). A recent retrospective cost-benefit analysis of ID hepatitis B vaccination reported a cost reduction exceeding 50% in comparison with a standard IM vaccine regimen (7). In fact the increase of anti-HBs antibodies is satisfactory after ID injection in all patients, a lower dose of the vaccine can be used, the cellular immune responsiveness to HBsAg can be easily assessed by the development of a skin reaction at the injection site (8) and thanks to the setup of this reaction there is no need of venous withdraws to test the serum anti-HBs concentration after the booster dose. On this debate, few shadows remains unsolved, because it is still not clear if celiac non-responders show an immunity energy since birth and do not respond since the first dose of vaccination or they lose their antibody protection with the flow of time, as physiologically happens in normal people, even if in a shorter period of time. Consequently, two subgroups of non-responders should be classified: the first group is the pure non-responders, that are celiac patients with a non-responsiveness since the first booster dose of HBV vaccine, and the second is the group of patients that lost their memory after a period of time after the vaccine injection. On this regard, in literature it is also demonstrated that immunological memory persists more than 10 years after the immunization of infants and adolescents with a primary course of vaccination (9) and there is general consensus that successfully vaccinated people who have lost their antibodies years after primary vaccination usually show a rapid anamnestic response when boosted (9). This means that the immunological memory for HBsAg can outlast antibody detection, providing long-term protection against the disease and the development of the carrier state. Therefore, until new data shed light on this issue good advice seems to be: 1) In consideration of the possible relationship between anti-HBs titers and compliance with gluten free diet (GFD), they should be always revaccinated after the decrease of specific celiac antibodies, which usually occurs after about 1 year of a strict GFD in order to maintain a high level of immunization. 2) After all, patients with CD should always receive a booster dose of vaccine every 10 years independently by their status of “pure” unresponsiveness. 3) HBV vaccine by intradermal route should be preferred instead of intramuscular route because of the use of lower doses of vaccine and the possibility to assess cellular immune responsiveness to HBsAg by the development of a skin reaction at the injection site (8).

Hepatitis B vaccination status and associated factors among health care workers in Burkina Faso

The purpose of this study was to evaluate anti-HBV vaccination status and factors associated with vaccination against HBV among health care workers in Burkina Faso. In August and September 2010, we conducted a cross-sectional study on health care workers having practiced in a health facility for at least three months. Data were collected using a self-administered questionnaire. Blood samples were collected from consenting participants to search for anti-HBs antibodies, markers of immune status. A total of 452 health care workers were surveyed. Among the respondents, 47.7 % had received at least one dose of HBV vaccine. The full immunization coverage against HBV was estimated at 10.9 %. Factors associated with vaccination status were age (p = 0.005), occupation (p = 0.005), and seniority in the profession (p = 0.001). Anti-HBs was found in 61.6 % of respondents, with significant differences (p = 0.01) between subjects who received at least one dose of vaccine (76.7 %) and those who reported never having been vaccinated (50.3 %). Hepatitis B vaccination coverage among health care workers is low in Burkina Faso, hence the need to promote vaccination against HBV in health facilities.

The risk factors of transmission after the implementation of the routine immunization among children exposed to HBV infected mothers in a developing area in northwest China

We aimed to evaluate the present situation and possible risk factors of HBV transmission after the implementation of the routine immunization among children exposed to HBV infected mothers in a developing area in northwest China. Two hundred and twenty one HBsAg carrier mothers and 247 children born to them were finally recruited in Wuwei city, Gangsu province, China in 2010. Serum samples were taken from those HBsAg carrier mothers and their children. Children who had detectable HBsAg or HBV DNA were considered to be HBV infection. Conditional logistic regression model was used to identify potential risk factors of HBV mother-to-child transmission. Of the 247 children born to HBsAg carrier mothers, 8 (3.24%) were HBsAg positive, 15 (6.07%) were HBV DNA positive. The rate of HBV mother-to-child transmission was 7.29% (18/247). The univariate analysis and multivariate analysis showed that maternal HBV DNA positive (OR=4.83, 95% CI: 1.38–16.98, p=0.0140), the delayed injection of the first dose of HBV vaccine after premature birth (OR=9.73, 95% CI: 1.78–53.21, p=0.0087) and the missing use of HBV vaccine (OR=8.29, 95% CI: 1.42–48.23, p=0.0186) were significantly associated with an increased risk for HBV mother-to-child transmission. The rate of HBV infection of the children received HBV vaccine and HBIG together after birth (2.56%, 4/156) was lower than those children received HBV vaccine alone (11.39%, 9/79) (χ2=7.83, p=0.0052). In conclusion, the rate of mother-to-child transmission of HBV was still high in the northwest of China. Besides the positivity of maternal HBV DNA and the missing of HBV vaccination after birth, the delayed injection of the first dose of HBV vaccine after premature birth was also a possible independent risk factor for HBV mother-to-child transmission. The HBV prevention and treatment guidelines should make it clear that all of the new born infants need to receive HBV vaccine injection after birth in 24h, including the premature infants.

Vaccination against hepatitis B with 4-double doses increases response rates and antibodies titers in HIV-infected adults

BackgroundAntibody responses to standard regimens of hepatitis B (HBV) vaccination are lower in HIV-infected subjects and the best hepatitis B vaccine schedule in this population is not known. ObjectiveTo assess the immunogenicity and to evaluate predictors of serologic response of a modified regimen of a HBV recombinant vaccine in a cohort of HIV-infected subjects. MethodsHIV-infected subjects received 4 doses (40μg) of a recombinant HBV vaccine at 0, 1, 2 and 6 months. Demographic information as well as CD4 cell count and plasma viral load were assessed at baseline. Protective and strong responses were defined as an anti-HBs titer ≥10mIU/mL and ≥100mIU/mL, respectively and were evaluated one month after the third and the fourth doses. Results163 HIV-infected individuals were evaluated 67 (40%) were male and median age was 37 years. Median CD4 cell count was 385cells/mm3 and 113 (70%) had undetectable HIV-1 viral load. Protective antibody response was observed in 83 and 91% and a strong antibody response was observed in 62 and 80% of the subjects after 3 and 4 doses, respectively.In a multivariate logistic model undetectable HIV-1 viral load and higher CD4 cell counts were independent predictors of a strong antibody response after 4 doses. Patients with undetectable HIV viral load were almost 3 times more likely to have anti-HBs titers above 100mIU/mL than those with detectable viral load. ConclusionsA 4-double-dose regimen of a recombinant HBV vaccine increased response rates and determined higher antibody titers which may translate in prolonged protection agains HBV. Inclusion of a fourth dose of HBV vaccine for HIV-infected subjects should be considered in the public health setting.

Clarification to Long-term anti-HBs antibody persistence and immune memory in children and adolescents who received routine childhood hepatitis B vaccination. Hum Vaccin Immunother 2012; 8:813-8

Purpose: This paper presents data from two studies that evaluated 5-year and 10-year 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]. Results: Anti-HBs antibody concentrations ³ 10mIU/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 years and 12−13 years, respectively 5−10 years after infant vaccination. One month post-challenge 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 ³ 100mIU/ml. Overall, 99.6% (95% CI: 98−100) and 97.2% (95% CI: 94.5−98.8) of subjects aged 7−8 years and 12−13 years mounted an anamnestic response to the HBV challenge dose, which was well-tolerated. Methods: Healthy children aged 7−8 years and adolescents aged 12−13 years received three doses of a monovalent pediatric HBV vaccine (10µg of HBsAg) before 18 months 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. Conclusions: A three-dose childhood HBV immunization regimen induced persistence of antibodies against HBV infection for 10 years, 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.

Patterns of hepatitis B infection in Egyptian children in the era of obligatory hepatitis B vaccination

Background and study aimsMass compulsory HBV vaccination was applied in Egypt in 1992. The first dose of vaccine is administered at 2months of age and routine screening of pregnant women for HBsAg is not applied. We aimed to evaluate the pattern of HBV infections after the implementation of HBV vaccination in Egyptian children. Patients and methodsFifty-six children with HBV infection presented to the Paediatric Hepatology Unit, Cairo University Children’s Hospital, over the period from 1992 to 2006. Their data were reviewed for risk factors, clinical, serological and histopathological profiles. These cases were followed-up for 6.3±3.4years. The data of those born before 1993 (did not receive HBV vaccine) (group I) was compared to those who received the vaccine (group II). ResultsSixty percent of HBV infected cases were born before 1993. Comparison of data of both groups revealed: (1) A significant younger age of onset in group II (3.34±3.31years vs. 9.84+2.95years; p⩽0.01). (2) Vertical transmission was a significant risk factor in group II. (3) Chronic hepatitis developed in almost half of cases in both groups but cirrhosis was diagnosed only in 4 cases (all from group I) (p=0.04). ConclusionVertically transmitted HBV infection is becoming an important risk factor for acquisition of HBV among children born after the era of mass vaccination in Egypt. Mass screening for HBsAg of pregnant Egyptian women and/or giving a birth dose of HBV vaccine is becoming mandatory with the increased incidence of vertical transmission.

GM-CSF Fails to Improve Immune Responses to Booster Hepatitis B Vaccination in HIV-Infected Individuals

Background:Hepatitis B (HBV) vaccination is an important preventive intervention for HIV-infected population. Data regarding booster HBV vaccine for persons with low HBV surface antibody (sAb) titers after vaccination in this immunocompromised population is lacking.Methods:We randomized 60 HIV-infected subjects lacking HBV protection after completion of 3 doses of HBV vaccine to receive a booster dose of HBV vaccine with 250mcg GM-CSF as an adjuvant or booster vaccine alone.Results:GM-CSF was safe with expected side effects. However, only 35% of persons receiving GM-CSF developed protective sAb while 50% in vaccine only arm developed protection (P = 0.47). Overall, only 28% of subjects maintained protective sAb 1 year after vaccination.Conclusions:GM-CSF failed to improve responses to the booster HBV vaccination. Overall, response was poor with only 42% of persons responding at one month post-vaccination confirming booster vaccination with the current HBV vaccine has poor immunogenicity among HIV-infected persons. Further research is needed to develop optimal vaccination strategies in HIV-infected persons.

Indoleamine 2,3-dioxygenase is increased in hemodialysis patients and affects immune response to hepatitis B vaccination

Background Acquired immunity is impaired in hemodialysis (HD) patients. Indoleamine 2,3-dioxygenase (IDO) is inducible by inflammation and through tryptophan depletion and generation of kynurenine pathway products suppresses adaptive immune response. In the present study plasma IDO levels were assessed in HD patients. Its effect on response to HBV vaccination program was evaluated. Patients and methods Sixty-six HD patients and twenty-four healthy volunteers enrolled into the study. All the HD patients were initially vaccinated with four double doses of recombinant HBV vaccine. All doses were repeated in patients who had not responded after complete first vaccination series. Only one boost dose was being administered in patients with initial adequate antibody levels against the HBV surface antigen (anti-HBs > 10 IU/L) who then presented with reduced anti-HBs levels. IDO, CRP, IL-6 and TNF-α were measured by means of ELISA. Results Compared to healthy volunteers, IDO levels were twice higher in HD patients. CRP, IL-6 and TNF-α were also much higher in HD patients. IDO levels were almost twice higher in HD patients with inadequate response to HBV vaccination, than in those with adequate immune response. CRP, IL-6 and TNF-α did not differ between the two patients’ groups. IDO was negatively correlated with all markers of inflammation in HD patients. Conclusion IDO is increased in HD patients. It is possible that after its initial upregulation due to chronic inflammation, IDO curtails its own provoking agent, i.e., inflammation. Increased IDO suppresses adaptive immunity in HD patients, as it is assessed by the response to HBV vaccination.

Spotlight on DTPa-HBV-IPV/Hib Vaccine (Infanrix hexa™)†

Infanrix hexa, administered intramuscularly, is a diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine, indicated for primary and booster vaccination of infants. Infanrix hexa should be administered as a two- or three-dose primary vaccination course in infants aged < or =6 months, followed by booster vaccination between 11 and 18 months of age, with an interval of at least 6 months between the last dose of primary vaccination and the booster dose. This spotlight reviews the immunogenicity and protective effectiveness, as well as the reactogenicity and safety of Infanrix hexa. Infanrix hexa as primary and booster vaccination was safe and highly immunogenic for all its component toxoids/antigens in infants aged <2 years, regardless of vaccination schedules. Its immunogenicity and safety profiles were generally similar to those of currently available vaccines, the diphtheria, tetanus and acellular pertussis-based pentavalent vaccines plus monovalent HBV or Hib vaccines. In large clinical studies, Infanrix hexa elicited a strong immune response against vaccine toxoids/antigens, as indicated by high seroprotection/seropositivity/vaccine response rates and geometric mean titers. Moreover, antibodies against vaccine toxoids/antigens persisted for up to a mean of approximately 6 years after booster vaccination, and the vaccine induced long-term immune memory against hepatitis B surface antigen and Hib antigen. A strong immune response against Infanrix hexa toxoids/antigens after primary vaccination was also induced in infants who had received a dose of HBV vaccine at birth and in pre-term infants, although the response in the latter group was somewhat lower than that in full-term infants. In addition, when coadministered with other childhood vaccines, the immunogenicity of Infanrix hexa or that of the concomitantly administered vaccine was generally not altered. Hexavalent vaccines, including Infanrix hexa, were protective against invasive Hib disease; Infanrix hexa is also expected to be protective against pertussis. Most solicited local and general symptoms with Infanrix hexa were mild to moderate in intensity and the vaccine was associated with few unsolicited adverse events. Available clinical data from more than 10 years' experience with the vaccine suggest that Infanrix hexa as primary and booster vaccination is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B and invasive Hib disease.

DTPa-HBV-IPV/Hib Vaccine (Infanrix hexa™)

Infanrix hexa, administered intramuscularly, is a diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine, indicated for primary and booster vaccination of infants. Infanrix hexa should be administered as a two- or three-dose primary vaccination course in infants aged <or=6 months, followed by booster vaccination between 11 and 18 months of age, with an interval of at least 6 months between the last dose of primary vaccination and the booster dose. This article reviews the immunogenicity and protective effectiveness, as well as the reactogenicity and safety of Infanrix hexa. Infanrix hexa as primary and booster vaccination was safe and highly immunogenic for all its component toxoids/antigens in infants aged <2 years, regardless of vaccination schedules. Its immunogenicity and safety profiles were generally similar to those of currently available vaccines, the diphtheria, tetanus and acellular pertussis-based pentavalent vaccines plus monovalent HBV or Hib vaccines. In large clinical studies, Infanrix hexa elicited a strong immune response against vaccine toxoids/antigens, as indicated by high seroprotection/seropositivity/vaccine response rates and geometric mean titres. Moreover, antibodies against vaccine toxoids/antigens persisted for up to a mean of approximately 6 years after booster vaccination, and the vaccine induced long-term immune memory against hepatitis B surface antigen and Hib antigen. A strong immune response against Infanrix hexa toxoids/antigens after primary vaccination was also induced in infants who had received a dose of HBV vaccine at birth and in pre-term infants, although the response in the latter group was somewhat lower than that in full-term infants. In addition, when coadministered with other childhood vaccines, the immunogenicity of Infanrix hexa or that of the concomitantly administered vaccine was generally not altered. Hexavalent vaccines, including Infanrix hexa, were protective against invasive Hib disease; Infanrix hexa is also expected to be protective against pertussis. Most solicited local and general symptoms with Infanrix hexa were mild to moderate in intensity and the vaccine was associated with few unsolicited adverse events. Available clinical data from more than 10 years' experience with the vaccine suggest that Infanrix hexa as primary and booster vaccination is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B and invasive Hib disease.

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 <10mIU/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 ≥10mIU/mL. All but one of the 14 boosted subjects responded to the additional HBV vaccine dose with anti-HBs concentrations ≥100mIU/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.

Immune memory to hepatitis B virus in 4-to-9-year old children vaccinated in infancy with four doses of hexavalent DTPa-HBV-IPV/Hib vaccine

The combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) vaccine produces similar hepatitis B responses as the HBV monovalent vaccine. Booster vaccination of immunocompetent individuals primed against hepatitis B in infancy is currently not recommended. We investigated persisting immunity to hepatitis B in 4-6 (Study A; 106745) and 7-9 (Study B; 106744) year-old children primed in infancy and boosted in the second year of life with DTPa-HBV-IPV/Hib. Immunity was assessed by measuring persisting anti-HBs antibodies and evaluating the response to a challenge dose of HBV vaccine. At 4-6 years of age 86.0% of 186 subjects had persisting anti-HBs ≥10mIU/ml increasing to 98.4% after the challenge. At 7-9 years of age, 78.0% of 186 subjects continued to have anti-HBs antibody concentrations ≥10mIU/ml, increasing to 98.9% after the challenge. In both studies anti-HBs antibody GMC rose >80-fold. An anamnestic response to the HBV challenge was observed in 95.7% and 98.9% of subjects in Studies A and B, respectively. In both studies, 87% of 38 subjects with initially undetectable circulating anti-HBs antibodies (