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.     

Seroprotection after recombinant hepatitis B vaccination among newborn infants: A review

Introduction

Hepatitis B vaccination starting at birth provides a safety net for infants exposed to hepatitis B virus (HBV) during delivery or in early life. Hepatitis B vaccine is recommended in the United States for infants prior to birthing facility discharge, and within the first 12 h of life for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. We performed a literature review and summarized the response to recombinant hepatitis B vaccine among infants.

Methods

Studies published between 1987 and 2011 assessing seroprotection from recombinant hepatitis B vaccine starting within the first 30 days of life were eligible. Seroprotection was defined using an antibody to hepatitis B surface antigen (anti-HBs) threshold of 10 mIU/mL at series completion. Infant seroprotection was compared in trial arms varying by maternal hepatitis B antigen status (e antigen [HBeAg], HBsAg), hepatitis B immune globulin (HBIG) administration, birth weight, vaccine dosage, schedule, and age at first dose.

Results

Forty-three studies were included. The median seroprotection proportion overall was 98% (range 52%, 100%). The final median seroprotection proportions did not vary appreciably by maternal HBsAg status, HBIG administration, or schedule. Higher compared to lower dosage resulted in earlier increases in anti-HBs but not in final seroprotection proportions. Infants with birth weights <2000 g compared to ≥2000 g had lower median seroprotection proportions (93% and 98%, respectively). Median seroprotection proportions were also lower when infants with birth weights <2000 g were vaccinated at 0–3 days of age compared to 1 month of age or older (68% versus 95%, respectively).

Conclusion

High levels of protection from recombinant hepatitis B vaccine are achieved in term infants vaccinated at birth, effectively preventing transmission of HBV and resultant morbidity and mortality. Implications, if any, for long-term protection are unknown for differences in responses among infants vaccinated at birth compared to ages older than 1 month.     

Hepatitis B vaccine immunogenicity among adults vaccinated during an outbreak response in an assisted living facility—Virginia, 2010

Background

Failure to adhere to infection control guidelines, especially during assisted monitoring of blood glucose, has caused multiple hepatitis B outbreaks in assisted living facilities (ALFs). In conjunction with the response to such an outbreak at an ALF (“Facility X”) where most residents had neuropsychiatric disorders, we evaluated seroprotection rates conferred by hepatitis B vaccine and assessed the influence of demographic factors on vaccine response.

Methods

Residents were screened for hepatitis B and C infection, and those susceptible were vaccinated against hepatitis A and hepatitis B with one dose of TWINRIX™ (GSK) given at 0, 1, and 7 months. Blood samples were collected 1–2 months after receipt of the third vaccine dose to test for antibody to hepatitis B surface antigen (anti-HBs).

Results

Of the 27 residents who had post-vaccination blood specimens collected, 22 (81%) achieved anti-HBs concentrations ≥10 mIU/mL. Neither age nor neuropsychiatric comorbidity was a significant determinant of seroprotection. Geometric mean concentration was lower among residents aged 60–74 years (74.3 mIU/mL) than among residents aged 46–59 years (105.3 mIU/mL) but highest among residents aged ≥75 years (122.5 mIU/mL). The effect of diabetes on vaccination response could not be examined because 16/17 (94%) diabetic residents had HBV infection by the time of investigation.

Conclusions

Adult vaccine recipients of all ages, even those over 60 years of age, demonstrated a robust capacity for achieving hepatitis B seroprotection in response to the combined hepatitis A/hepatitis B vaccine. The role for vaccination in interrupting HBV transmission during an outbreak remains unclear, but concerns about age-related response to hepatitis B vaccine may be insufficient to justify foregoing vaccination of susceptible residents of ALFs.     

Surface antibody and cytokine response to recombinant Chinese hamster ovary cell (CHO) hepatitis B vaccine

Objective

To compare the immune responses of the 10 μg and 20 μg doses of CHO hepatitis B vaccine on adults.

Methods

Adults aged 18-45 years who gave a history of never having received hepatitis B vaccine and lacked serologic evidence of infection to hepatitis B virus (HBV) infection or previous vaccination were enrolled into the study. A total of 642 eligible participants were randomized to receive 3 doses of either the 10 μg or the 20 μg formulation of CHO hepatitis B vaccine in a 0-1-6 month schedule. Each study subject had a serologic specimen collected one month following the third vaccine dose that was tested for markers of HBV infection and anti-HBs by Abbott I2000. Persons who tested negative for anti-HBs negative persons were tested for HBV DNA. Logistic regression was used to identify factors associated with antibody response. Among the participants, 153 subjects had their lymphocytes cultivated and tested for cytokine production. Enzyme-linked immunospot (ELISPOT) was used to test spot numbers of IL-4, IFN-γ which produced by lymphocyte.

Results

The anti-HBs seroconversion rate was 88.8% (95% CI: 85.4-92.2%) and 95.3% (95% CI: 93.0-97.6%), respectively in 10 μg and 20 μg group. Geometric mean titers (GMT) were 173.42 mIU/ml and 585.51 mIU/ml, respectively in 10 μg and 20 μg groups. Multivariate analysis demonstrated that diabetes, spouse is hepatitis B virus infector, older age and receipt of the 10 μg dose were all negatively associated with antibody response (P < .05). Cellular immunity results showed: IL-4 immunity spot numbers in 20 μg group was higher than 10 μg group. With anti-HBs increased, the IL-4 immunity spot numbers increased significantly which had significant positive correlation (Spearman coefficient = 0.538, P < 0.0001). IFN-γ spot numbers had no statistical significant between the two groups.

Conclusion

The humoral immunity and cytokines response among the group that received the 20 μg CHO hepatitis B vaccine dose was superior compared to the group that received the 10 μg dose. The 20 μg dose of CHO hepatitis B vaccine should be prioritized for adult vaccination programs in China.     

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.     

Evaluation of hepatitis B vaccine immunogenicity among older adults during an outbreak response in assisted living facilities

Background

During the past decade, in the United States, an increasing number of hepatitis B outbreaks have been reported in assisted living facilities (ALFs) as a result of breaches in infection control practices. We evaluated the seroprotection rates conferred by hepatitis B vaccine among older adults during a response to an outbreak that occurred in multiple ALFs and assessed the influence of demographic and clinical factors on vaccine response.

Methods

Residents were screened for hepatitis B and C infection prior to vaccination and susceptible residents were vaccinated against hepatitis B with one dose of 20 μg Engerix-B™ (GSK) given at 0, 1, and 4 months. Blood samples were collected 80-90 days after the third vaccine dose to test for anti-HBs levels.

Results

Of the 48 residents who had post-vaccination blood specimens collected after the third vaccine dose, 16 (33.3%) achieved anti-HBs concentration ≥10 mIU/mL. Age was a significant determinant of seroprotection with rates decreasing from 88% among persons aged ≤60 years to 12% among persons aged ≥90 years (p = 0.001). Geometric mean concentrations were higher among non-diabetic than diabetic residents, however, the difference was not statistically significant (5.1 vs. 3.8 mIU/mL, p = 0.7).

Conclusions

These findings highlight that hepatitis B vaccination is of limited effectiveness when administered to older adults. Improvements in infection control and vaccination at earlier ages might be necessary to prevent spread of infection in ALFs.     

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.     

Persistence of antibodies and immune memory to hepatitis B vaccine 20 years after infant vaccination in Thailand

Booster vaccination against hepatitis B (HBV) is not currently recommended, although debate continues on the duration of protection after priming. We assessed antibody persistence and immune memory to hepatitis B 20 years after priming with a recombinant HBV-vaccine during infancy. Infants were vaccinated at birth, 1, 2 and 12 months of age. A subset received a booster dose at Year 5. Antibody persistence was measured approximately yearly until Year 20. Immune memory was assessed by administration of HBV booster dose. At Year 20, anti-HBs seroprotection rates and GMCs tended to be higher in Year 5 boosted than unboosted recipients (83.9% versus 60.5%). After the Year 20 booster dose, anti-HBs anamnestic responses were within the same range 95.8% of subjects in both groups. Primary and booster vaccination with HBV-vaccine in infants induces sustained seroprotection and immune memory against hepatitis B for up to 20 years. Higher persisting seroprotection rates in subjects boosted at Year 5 did not translate into apparent differences in immune memory in a high endemic country.     

Significance and anamnestic response in isolated hepatitis B core antibody-positive individuals 18 years after neonatal hepatitis B virus vaccination in Taiwan

Aim

To investigate the significance of isolated hepatitis B core antibody (anti-HBc) and to analyze the response to hepatitis B virus (HBV) booster vaccination in young adults with isolated anti-HBc who had been fully vaccinated with HBV vaccine as infants.

Materials and methods

We screened 1734 new university entrants who had been fully vaccinated against HBV in infancy for the presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and anti-HBc upon university entry. Results positive for isolated anti-HBc were reconfirmed by testing for the presence of HBsAg and anti-HBc once more, and further evaluated for anti-HCV, anti-HIV, and HBV DNA status 6 months later. Students were also offered HBV booster vaccinations at that time. Geometric mean titers (GMT) of anti-HBs after one booster dose of HBV were compared between students with isolated anti-HBc and students with HBV naïve status.

Results

The overall prevalence of isolated anti-HBc in our student cohort was 1.2% (21 of 1734). No evidence of occult HBV infection was observed. A “booster” anamnestic response (anti-HBs titer ≥10 mIU/mL) was noted in 95% (20 of 21) of subjects with isolated anti-HBc. After re-measurement of anti-HBc, 13 (62%) of the 21 subjects with isolated anti-HBc were reclassified as having resolved HBV infection with a loss of anti-HBs. In the remaining 8 subjects (38%), isolated anti-HBc was determined to be false positive. The HBV status of these 8 subjects was HBV naïve due to the waning-off effect of anti-HBs of the neonatal HBV vaccination. There was no significant difference in anamnestic response to a single HBV booster dose of vaccine between students with isolated anti-HBc (n = 13) and those with HBV naïve (n = 323) status (GMT 50.6 vs 47.7 mIU/mL, P = 0.90).

Conclusion

The presence of isolated anti-HBc 18 years after HBV vaccination can be attributed to post-HBV infection with a loss of anti-HBs and to a decline in anti-HBs elicited by vaccine. A single HBV booster dose of vaccine is recommended for subjects with isolated anti-HBc who were fully vaccinated with HBV vaccine as infants. This finding needs to be replicated in further studies with larger cohorts.     

Post-vaccination serological test results of infants at risk of perinatal transmission of hepatitis B using an intensified follow-up programme in a London centre

Immunisation of infants born to hepatitis B virus (HBV) infected mothers is an important public health measure to prevent mother-to-child transmission of HBV. Post-vaccination serological tests (PVST) inform the success of the infant HBV immunisation programme and identify infected infants. Previous studies suggested that the rates of PVST in the UK programme were unsatisfactory. We introduced an intensified local follow-up programme and offered an earlier PVST 2–3 months after the third vaccination at age 4–5 months. Of 219 infants born between 2009 and 2011, 193 infants (88.1%) had at least one PVST: 145 (66.2%) early; 94 (42.9%) standard; 46 (21.0%) both and 26 (11.9%) never tested. Twenty-four infants were identified as high risk for mother-to-child transmission according to national criteria and received both hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine at birth. These infants had a significantly lower hepatitis B surface antibody (anti-HBs) levels at early PVST compared to the lower risk group who received hepatitis B vaccine only (median of 59 vs. 376 mIU/ml, P = 0.006). None of the infants tested were infected with hepatitis B. This study illustrates that the rate of PVST can be improved by using an intensified follow-up programme offering an early PVST. The significantly lower anti-HBs levels in the HBIG subgroup is of concern as this group of infants is already at higher risk for acquiring HBV infection. Infants with poor antibody responses can be identified by an early PVST and offered a timely extra booster dose.     

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.     

Anti-hepatitis B core antibody is not required for prevaccination screening in healthcare workers

Vaccination against hepatitis B virus (HBV) is recommended for health care workers (HCWs), but it is not clear whether HBV vaccination is required for HCWs who have isolated antibody to hepatitis B core antigen (anti-HBc), or whether prevaccination screening for anti-HBc is needed in HCWs. Among 1812 HCWs, subjects with isolated anti-HBc and those with no HBV markers (control) were screened. The anamnestic response (antibody to hepatitis B surface antigen over 50 mIU/mL after the first vaccine injection) was compared prospectively between the two groups. The prevalence of isolated anti-HBc was 2.3%. Their anamnestic response was lower than that of controls (27.5% vs. 46.9%, P = 0.020). The subjects who had isolated anti-HBc were older and predominantly male, compared with the controls. Multivariate analysis revealed that age (odds ratio [OR], 0.67; confidence interval [CI], 0.51-0.90) and prior vaccination (OR, 3.36; CI, 2.04-5.54) were independent predictors of the anamnestic response, regardless of the anti-HBc status. Serum HBV DNA was not detected in any subject. Anti-HBs seroconversion was achieved in most of the anti-HBc-positive subjects after full vaccination, and the rate was comparable with controls (89.5% vs. 96.6%, P = 0.067). Isolated anti-HBc-positive HCWs are rare and most of them respond to vaccination. Anti-HBc testing is not a prerequisite for vaccination. This serology suggests a loss of acquired anti-HBs rather than occult HBV infection. Their reduced immunity to vaccination may be related to old age.     

Induction of a robust T- and B-cell immune response in non- and low-responders to conventional vaccination against hepatitis B by using a third generation PreS/S vaccine

Non-responsiveness to conventional hepatitis B vaccines in individuals at high risk of exposure to hepatitis B virus (HBV) is an important public health problem and of particular relevance in health care providers. Yeast-derived conventional HBsAg vaccines fail to induce protective antibody titers in up to 10% of immune competent vaccinees. Therefore, a third generation HBV vaccine, Sci-B-Vac™, was developed which contains in addition to the small S antigen the PreS1 and PreS2 antigens. This vaccine proved to induce a highly potent cellular and humoral immune response in healthy individuals as well as protective antibody levels in non- and low-responders to conventional HBV vaccines. The aim of the study was to examine whether Sci-B-Vac™ triggers cellular and humoral immunity in individuals who failed immunization with conventional vaccines. We immunized 21 volunteers (15 non- and 6 low-responders) according to the standard vaccination schedule (0, 4 and 24 weeks), determined the cellular immunity by proliferation assay and interferon (IFN)-γ ELISpot and measured the anti-HBs antibody titers prior to each vaccination and four weeks after the third vaccine dose. Following three vaccinations, PreS/S-specific T-cell proliferation was detected in 8 out of 15 non-responders and 5 out of 6 low-responders. Specific IFN-γ responses were measured in 2 out of 15 non-responders and 4 out of 6 low-responders. All but one (20/21) study participants developed anti-HBs titers ≥10 IU/l after three vaccinations. Anti-HBs ≥100 IU/L were detected in 12 out of 15 non-responders and in 6 out of 6 low-responders. Anti-HBs ≥10 IU/l and <100 IU/l were found in 2 non-responders. These results indicate that Sci-B-Vac™ induces cellular immunity as well as protective anti-HBs antibody titers in non- and low-responders. In conclusion, these results confirm that Sci-B-Vac™ should be administered to non-responders to conventional HBV vaccines and patients with impaired immune function.     

Effects of hepatitis B immunization on prevention of mother-to-infant transmission of hepatitis B virus and on the immune response of infants towards hepatitis B vaccine

Background

Combined immunization with hepatitis B immunoglobulin (HBIG) plus hepatitis B vaccine (HB vaccine) can effectively prevent perinatal transmission of hepatitis B virus (HBV). With the universal administration of HB vaccine, anti-HBs conferred by HB vaccine can be found increasingly in pregnant women, and maternal anti-HBs can be passed through the placenta. This study was designed to evaluate the effect of hepatitis B immunization on preventing mother-to-infant transmission of HBV and on the immune response of infants towards HB vaccine.

Method

From 2008 to 2013, a prospective study was conducted in 15 centers in China. HBsAg-positive pregnant women and their infants aged 8–12 months who completed immunoprophylaxis were enrolled in the study and tested for HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc). Antepartum administration of HBIG to HBsAg-positive women was based on individual preference. HBsAg-negative pregnant women and their infants of 7–24 months old who received HB vaccines series were enrolled and tests of their HBV markers were performed.

Results

1202 HBsAg-positive mothers and their infants aged 8–12 months were studied and 40 infants were found to be HBsAg positive with the immunoprophylaxis failure rate of 3.3%. Infants with immunoprophylaxis failure were all born to HBeAg-positive mothers of HBV-DNA ≥ 6 log₁₀ copies/ml. Among infants of HBeAg-positive mothers, immunoprophylaxis failure rate in vaccine plus HBIG group, 7.9% (29/367), was significantly lower than the vaccine-only group, 16.9% (11/65), p = 0.021; there was no significant difference in the immunoprophylaxis failure rate whether or not antepartum HBIG was given to the pregnant woman, 10.3% (10/97) vs 9.0% (30/335), p = 0.685. Anti-HBs positive rate was 56.3% (3883/6899) among HBsAg-negative pregnant women and anti-HBs positive rate was 94.2% in cord blood of anti-HBs-positive mothers. After completing the HB vaccine series, anti-HBs positive rate among infants with maternal anti-HBs titers of <10 IU/L, 10–500 IU/L and ≥500 IU/L was 90.3% (168/186), 90.5% (219/242) and 80.2% (89/111) respectively, p = 0.011. Median titers of anti-HBs (IU/L) among infants in the three groups was 344.2, 231.9 and 161.1 respectively, p = 0.020.

Conclusions

HBIG plus HB vaccine can effectively prevent mother-to-infant transmission of HBV, but no HBV breakthrough infection was observed in infants born to HBeAg-negative mothers who received HB vaccine with or without HBIG after birth. Antepartum injection of HBIG has no effect on preventing HBV mother-to-infant transmission. High maternal titer of anti-HBs can transplacentally impair immune response of infants towards HB vaccine.     

Effect of age and frequency of injections on immune response to hepatitis B vaccination in drug users

Despite the high immunogenicity of the hepatitis B vaccine, evidence suggests that immunological response in drug users is impaired compared to the general population.A sample of not-in-treatment adult drug users from two communities in Houston, TX, USA, susceptible to hepatitis B virus (HBV), was sampled via outreach workers and referral methodology. Participants were randomized to either the standard multi-dose hepatitis B vaccine schedule (0, 1, and 6 months) or to an accelerated (0, 1, and 2 months) schedule. The participants were followed for 1 year. Antibody levels were measured at 2, 6 and 12 months after enrollment in order to determine the immune responses.At 12 months, cumulative adequate protective response was achieved in 65% of the HBV susceptible subgroup using both the standard and accelerated schedules. The standard group had a higher mean antibody titer (184.6 mIU/mL vs 57.6 mIU/mL). But at 6 months, seroconversion at the adequate protective response was reached by a higher proportion of participants and the mean antibody titer was also higher in the accelerated schedule group (104.8 mIU/mL vs. 64.3 mIU/mL). Multivariate analyses indicated a 63% increased risk of non-response for participants 40 years or older (p = 0.046). Injecting drugs more than once a day was also highly associated with the risk of non-response (p = 0.016).Conclusions from this research will guide the development of future vaccination programs that anticipate other prevalent chronic conditions, susceptibilities, and risk-taking behaviors of hard-to-reach populations.     

The effect of diabetes mellitus on immunological response to hepatitis B virus vaccine in individuals with chronic kidney disease: A meta-analysis of current literature

Background

Patients with chronic kidney disease (CKD) often fail to produce protective antibodies to hepatitis B virus (HBV) surface antigen after vaccination. Diabetes mellitus (DM) is the most common cause of CKD; however it is not clear whether it affects immunological response to HBV vaccine in these patients.

Aims

We aimed to evaluate the immunological response to HBV vaccine in diabetic patients with CKD by conducting a meta-analysis of the current literature.

Methods

Only studies that evaluated the seroprotection rate for diabetic against non-diabetic CKD patients or the immunological response of these groups to HBV vaccine were included. We applied the random effects model of DerSimonian and Laird, with heterogeneity (Q statistic), publication bias (Egger and Begg test) and sensitivity analyses. The rate of patients showing seroprotective anti-HBsAg titers (>10 IU/mL) at completion of HBV vaccination schedule in the diabetic versus the non-diabetic CKD patients was set as our end-point of interest.

Results

We identified seven studies that fulfilled our inclusion criteria involving 15,073 unique patients with CKD. Aggregation of study results showed a significant decrease in response rates among the diabetic versus the non-diabetic patients [pooled odds ratio = 0.58 (95% CI 0.37–0.89), Q(6) = 11.3, I² = 50%]. The P-value was 0.07 for our test of heterogeneity.

Conclusions

Our meta-analysis determined that HBV vaccination's seroprotection rate in diabetic CKD patients is significantly lower than that in non-diabetic CKD patients. Therefore, using vaccine adjuvants such as oral levamisole, granulocyte macrophage-colony stimulating factor or intradermal injection might be advisable in these patients.     

Antibody response following hepatitis B vaccination in dialysis patients: Does depression and life quality matter?

Previously, it was demonstrated that antibody production against hepatitis B virus (HBV) surface antigen (anti-HBs) achieved in hemodialysis patients is suboptimal. Decreased health-related quality of life (HRQOL) and depression is common among hemodialysis patients. This study evaluated whether HRQOL and depressive behavior are associated with antibody response against HBV surface antigen in hemodialysis patients. Depressive symptoms and HRQOL were assessed by Beck Depression Inventory (BDI) and Medical Outcomes Study Short Form (SF-36), respectively. Patients were separated into non-seroconversion (anti-HBs antibody titers <10 IU/L) and seroconversion (anti-HBs antibody titers ≥10 IU/L) groups. Among 188 patients, 37 (19.7%) were diagnosed as nonresponsive to vaccination (anti-HBs antibody titers <10 1U/L). Anti-HBs response is positively associated with Physical Component Summary Score of SF-36 (odds ratio: 1.44; P: 0.009) and albumin (odds ratio: 10.615, P: 0.007), and negatively with BDI score (odds ratio: 0.903, P: 0.007). We concluded that HRQOL and depression is closely related with antibody response following HBV vaccine in hemodialysis patients.     

Long-term antibody persistence and immune memory to hepatitis B virus in adult celiac patients vaccinated as adolescents

Aim of this study was to investigate the anti-HBs antibody persistence and immune memory to hepatitis B virus in adult celiacs vaccinated as adolescents and the effect of a booster administration in non-protected individuals. Eleven years after primary vaccination, the proportion of vaccinees with titres ≥10 mIU/ml and antibody geometric mean concentrations (GMCs) were lower among celiac patients than among controls (68.6% vs 91.7%, p < 0.01; GMCs 29.38 mIU/ml vs 250.6 mIU/ml, p < 0.001). Participants with anti-HBs below 10 mIU/ml received a booster dose and were retested 2 weeks later to assess the anamnestic response. Post-booster anti-HBs levels were still <10 mIU/ml in 71.4% celiacs and 25% controls (p < 0.01).Our findings indicate that the prevalence of seroprotective levels of anti-HBs detected eleven years after primary immunization as well as the frequency of response to a booster dose of vaccine are lower in celiac patients compared to healthy controls.     

Interchangeability of Quinvaxem during primary vaccination schedules: Results from a phase IV,single-blind,randomized, controlled,single-center,non-inferiority study

Combination vaccines against diphtheria, tetanus and pertussis (DTP) represent the core of childhood vaccination programs. Quinvaxem, a fully-liquid, pentavalent combination vaccine containing inactivated hepatitis B (HepB), Haemophilus influenzae type b (Hib) and whole-cell pertussis (wP) antigens, and tetanus and diphtheria toxoids, has been shown to be suitable for boosting children primed in infancy with another DTwP–HepB–Hib vaccine. This single-blind, randomized, controlled study was designed to demonstrate non-inferiority of a primary vaccination course (6–10–14 week schedule) of Tritanrix HB + Hib (first dose) and Quinvaxem (second/third doses) versus three doses of Quinvaxem with respect to the seroprotection/seroconversion rates for all antigens one month after vaccination course completion. Four hundred healthy subjects eligible for the local Expanded Program on Immunization were enrolled and equally randomized to the two treatment regimens. All subjects achieved seroprotection for tetanus and Hib, all except one for diphtheria, and all except two achieved seroconversion against Bordetella pertussis. Seroprotection against hepatitis B was achieved by 97.4% of Tritanrix HB + Hib followed by Quinvaxem and 94.9% of Quinvaxem subjects. Therefore, one month after vaccination course completion, seroprotection rates (seroconversion rate for B. pertussis) of Tritanrix HB + Hib followed by Quinvaxem were non-inferior to those elicited by Quinvaxem only, thus meeting the primary objective. Adverse events were comparable between the groups and were in line with the safety profile of the vaccines. The switch of vaccine had no apparent effect on safety endpoints. Our results support the use of Quinvaxem interchangeably with Tritanrix HB + Hib in a primary vaccination course and provides further evidence for the interchangeability of pentavalent vaccines (Clinical Trials.gov registry: NCT01357720).     

Strong influence of human leukocyte antigen-DP variants on response to hepatitis B vaccine in a Japanese population

Genome-wide association studies (GWASs) have reported that human leukocyte antigen (HLA) variants are associated with chronic hepatitis B, spontaneous hepatitis B virus (HBV) clearance, and response to hepatitis B vaccine. Single nucleotide polymorphisms (SNPs) in HLA-DP (rs9277535 and rs3077) and HLA-DQ (rs2856718 and rs7453920) have been repeatedly associated with chronic hepatitis B and spontaneous HBV clearance. However, the data on the SNPs associated with response to hepatitis B vaccine are inconclusive. The objective of this study was to determine whether these four HLA SNPs that have been identified as risk loci for chronic HBV infection are associated with response to hepatitis B vaccine in a Japanese population. We enrolled 278 medical students who received hepatitis B vaccination and measured anti-hepatitis B surface (HBs) antibody titers 1 month after a three-dose vaccination series. We found that rs9277535 and rs3077 in HLA-DP were strongly associated with response to hepatitis B vaccine (odds ratio [OR] = 0.31 and 0.32, P = 0.004 and 0.010, respectively). These two SNPs were significantly associated with anti-HBs titers in an allele-dependent manner. On the other hand, rs2856718 and rs7453920 in HLA-DQ were not associated with response to hepatitis B vaccine. These results indicate that rs9277535 and rs3077 in HLA-DP are the major determinants of response to hepatitis B vaccine, whereas rs2856718 and rs7453920 in HLA-DQ have little effect on the immune response to hepatitis B vaccine.