anti-HBs Seroconversion Rates Research Articles

Clinical study of hepatitis B vaccine in achieving hepatitis B surface antibody seroconversion in patients with functional cure

Hepatitis B Surface Antigen (HBsAg) seroclearance is the highest treatment goal recommended by the current guidelines for hepatitis B. Levels of antibodies to HBsAg (anti-HBs) are strongly associated with HBsAg recurrence, but hepatitis B vaccination may increase the anti-HBs seroconversion rate and reduce recurrence. We conducted a retrospective clinical study to ascertain the effect of this vaccination on the seroconversion rate and levels of protective anti-HBs after HBsAg. In this retrospective study, we distributed a questionnaire through an online survey platform to collect information related to hepatitis B vaccination in patients with functional cure of hepatitis B with Interferon-α (IFNα) therapy. We enrolled 320 patients who achieved functional cure from IFNα therapy. Of these, 219 patients had received hepatitis B vaccination according to their personal preference and drug accessibility after HBsAg seroclearance, whereas the remaining 101 patients did not receive hepatitis B vaccination. The anti-HBs seroconversion rate of 78.1% in the vaccinated group was significantly greater than that in the unvaccinated group (41.6%) (p < 0.001). Stratified comparisons with anti-HBs of ≥ 100 IU/L and ≥ 300 IU/L showed that both proportions in the vaccinated group were greater than those in the unvaccinated group (71.2% vs. 32.7% and 56.2% vs. 17.8%, respectively, all p-values < 0.001). Logistic regression analysis showed that the odds ratio of vaccination was 4.427, which was the strongest influencing factor for anti-HBs, reaching 100 IU/L or higher. Hepatitis B vaccination in patients after HBsAg seroclearance not only increased the anti-HBs seroconversion rate but also significantly increased antibody levels, with good safety, indicating the clinical value of vaccine therapy for patients with functional cure.

Seroconversion of hepatitis B surface antigen among those with previously successful immune response in Southern China

ABSTRACT Recommendations promoted worldwide have suggested a period of protection lasting more than 20 years against hepatitis B (HB) following primary immunization. Starting in 1987, universal HB vaccinations were carried out in Long An County, Guangxi Province, one of the earliest counties in which plasma-derived HB vaccine was delivered to newborns across China. Data collection targeted toward understanding the long term (26–33 years since primary immunization) immune effects of the plasma-derived HB vaccine was conducted in 2015; a second data collection was carried out in 2019 to assess seroconversion in the same cohort. This study qualitatively compared positive vs negative results and quantitatively assessed HB biomarkers – HB surface antigen (HBsAg), antibody to HBsAg (anti-HBs), HB e-antigen (HBeAg), antibody to HBeAg (anti-HBe), and antibody to HB core antigen (anti-HBc) – in serum 26–33 years after the full initial course of HB vaccination, then analyzed anti-HBs seroconversion using the two-phase sampling method in the same cohort and calculated the anti-HBs seroconversion rate from 2015 to 2019. The protective sero-conversion rate (anti-HBs ≥10mIU/mL) was 37.6% (192/511); the HBsAg-positive rate was 5.3% (27/511); the anti-HBs mean geometric titer (GMT) was 11.1 mIU/mL. Among the 143 participants involved in both 2015 and 2019 data collections, the seroconversion rate was 3.5% (5/143); two individuals had protective anti-HBs levels in 2015. These findings indicate that anti-HBs status can be seroconverted to a protective concentration level 4 years earlier in a high HBV epidemic region. The role of genomic mutations and the disappearance of immune memory and seroconversion should be investigated.

Immune responses to hepatitis B vaccination after hematopoietic stem cell transplantation in pediatric and young adult patients.

Hematopoietic stem cell transplantation (HSCT) recipients require hepatitis B (HBV) revaccination. Hepatitis B surface antibody (anti-HBs) seroconversion rates after revaccination range from 64% to 79% in these patients. The seroconversion rate and factors associated with non-seroconversion have not been clearly elucidated in pediatric and young adult recipients after HSCT. To evaluate anti-HBs seroconversion rates in pediatric and young adult patients revaccinated after HSCT, and to identify factors associated with non-seroconversion. The current study was prospective and cross-sectional. Post-HSCT recipients aged ≤25years who had completed a course of three HBV revaccinations were recruited, and their anti-HBs titers were assessed. Non-seroconverted patients were administered a fourth vaccination. Those who subsequently remained seronegative were administered two additional vaccinations. Those who remained seronegative after all six vaccinations were defined as non-responders. A total of 118 patients were enrolled. The HBV-containing vaccines used included DTaP-IPV-HBV-Hib, DTwP-HBV-Hib, and monovalent vaccines. The anti-HBs seroconversion rate after three revaccinations was 82% (95% confidence interval [CI], 73.7-89.2). One patient (0.8%) was classified as non-responder. Factors associated with non-seroconversion after three revaccinations included cytomegalovirus (CMV) reactivation (odds ratio [OR] 10.63, 95% CI 1.16-97.00), anti-HBs seronegativity before HSCT (OR 7.01, 95% CI 1.55-31.78) and three DTwP-HBV-Hib revaccinations (OR 11.71, 95% CI 1.43-96.26). In the current study the anti-HBs seroconversion rate after three HBV revaccinations was excellent. CMV reactivation, anti-HBs seronegativity before HSCT, and three DTwP-HBV-Hib revaccinations were associated with non-seroconversion, but the non-responder rate was low.

Short-term immunogenicity of standard and accelerated hepatitis B virus vaccination schedules in healthy adults: a comparative field study in China.

World Health Organization recommends hepatitis B virus (HBV) immunization at 0, 1, and 6 months. However, studies have suggested that shortening the interval between the first and last HBV immunization can improve completion rates. Less clear is whether accelerated immunization is as immunogenic as standard immunization. Thus, the present study aimed to compare the short-term immunogenicity of yeast-derived hepatitis B vaccine in healthy adults immunized on an accelerated or standard schedule. Between June 2013 and March 2014, individuals from Jinfeng and Longmen, China were randomly assigned to receive the vaccine on an accelerated schedule (at 0, 1, and 2 months; n=201) or a standard schedule (at 0, 1, and 6 months; n=206). Subjects filled out a questionnaire asking about demographic and other health data, and they underwent physical examination. Blood was assayed for HBV surface antigen and HBV surface antibody (HBsAb) at 1–2 months after the three-dose schedule. Multivariate binary logistic regression was used to determine whether the rate of anti-HBs seroconversion differed with immunization schedule. Covariance analysis was used to compare geometric mean HBsAb concentration between the two schedules. The anti-HBs seroconversion rate was 84.6% in the accelerated group and 90.3% in the standard group. After controlling for several potential confounders, the accelerated schedule was associated with significantly lower anti-HBs seroconversion rate (OR: 0.560, 95% CI: 0.318–0.988). Similarly, the accelerated schedule was associated with significantly lower geometric mean HBsAb concentration. These results suggest that the standard schedule is more likely to lead to anti-HBs seroconversion and higher HBsAb levels in adults.

Analysis of hepatitis B surface antigen (HBsAg) using high-sensitivity HBsAg assays in hepatitis B virus carriers in whom HBsAg seroclearance was confirmed by conventional assays.

We investigated the utility of high-sensitivity hepatitis B surface antigen (HBsAg) assays compared with conventional HBsAg assays. Using serum samples from 114 hepatitis B virus (HBV) carriers in whom HBsAg seroclearance was confirmed by conventional HBsAg assays (cut-off value, 0.05IU/mL), the amount of HBsAg was re-examined by high-sensitivity HBsAg assays (cut-off value, 0.005IU/mL). Cases negative for HBsAg in both assays were defined as consistent cases, and cases positive for HBsAg in the high-sensitivity HBsAg assay only were defined as discrepant cases. There were 55 (48.2%) discrepant cases, and the range of HBsAg titers determined by high-sensitivity HBsAg assays was 0.005-0.056IU/mL. Multivariate analysis showed that the presence of nucleos(t)ide analog therapy, liver cirrhosis, and negative anti-HBs contributed to the discrepancies between the two assays. Cumulative anti-HBs positivity rates among discrepant cases were 12.7%, 17.2%, 38.8%, and 43.9% at baseline, 1year, 3years, and 5years, respectively, whereas the corresponding rates among consistent cases were 50.8%, 56.0%, 61.7%, and 68.0%, respectively. Hepatitis B virus DNA negativity rates were 56.4% and 81.4% at baseline, 51.3% and 83.3% at 1year, and 36.8% and 95.7% at 3years, among discrepant and consistent cases, respectively. Hepatitis B surface antigen reversion was observed only in discrepant cases. Re-examination by high-sensitivity HBsAg assays revealed that HBsAg was positive in approximately 50% of cases. Cumulative anti-HBs seroconversion rates and HBV-DNA seroclearance rates were lower in these cases, suggesting a population at risk for HBsAg reversion.

Persistence of Hepatitis B Immunity Following 3-dose Infant Primary Series in HIV-infected Thai Adolescents and Immunologic Response to Revaccination.

HIV infection may alter immunologic response and the establishment of immune memory to infant hepatitis B virus (HBV) vaccination. This study aimed to determine the need to revaccinate perinatally HIV-infected Thai adolescents. Cross-sectional serologic tests for HBV, including hepatitis B surface antigen, anti-hepatitis B surface antibody (anti-HBs) and anti-hepatitis B core antibody (anti-HBc), were performed in perinatally HIV-infected adolescents. Adolescents having anti-HBs <100 mIU/mL with negative anti-HBc and immune reconstitution from highly active antiretroviral therapy (HAART) were revaccinated using regular (10 μg) 3-dose schedule given intramuscularly at 0-, 2- and 6-month intervals. Of 193 adolescents who received 3-dose infant HBV vaccination, 6 were receiving HAART during vaccination, median (interquartile range) current age 14.5 (11.7-16.2) years, 7 (3.6%) had positive anti-HBc (indicating breakthrough infection), of which 4 (2%) had positive hepatitis B surface antigen (indicating chronic infection). Twenty-two (11.4%) adolescents had protective anti-HBs concentration >10 mIU/mL. Of 164 revaccinated adolescents, 142 (86.6%) had HIV viral load <40 copies/mL. Anti-HBs seroconversion rates >10 mIU/mL were 58.0% (94/162) after the first dose and 97.5% (158/162) after the third dose of revaccination. Forty-five (28%) subjects responded to the first dose with anti-HBs antibody ≥100 mIU/mL had a shorter median duration with CD4 count <15% than their counterparts (6.2 vs. 11.1 months; P = 0.049). Only half of perinatally HIV-infected adolescents were able to elicit anti-HBs response with a single-dose HBV vaccine. Revaccination with 3-dose schedule is required in perinatally HIV-infected adolescents who did not initiate HAART at the time of infant vaccination.

A Single Center Analysis of the Positivity of Hepatitis B Antibody after Neonatal Vaccination Program in Korea

The antibody to hepatitis B surface antigen (anti-HBs) seropositivity rate after 3 doses of hepatitis B virus (HBV) vaccination during infancy period is known to be higher than 90%. However, a considerable number of vaccines do not form protective anti-HBs or chronologic decrease of anti-HBs. We retrospectively collected data of HBV serologic test results in 20,738 individuals from 2000 to 2015. After exclusion criteria were applied, 19,072 individuals were included. We analyzed the anti-HBs seropositivity rate, anti-HBs disappearance rate, anti-HBs positive seroconversion rate after receiving a booster vaccine, and the difference in anti-HBs positivity between the 2 groups; group A (born before 2005, while both recombinant vaccines and plasma-derived vaccines were used) and group B (born after 2005, when only recombinant vaccines were used by national regulation). The anti-HBs seropositivity rate was 55.8%, but there was a significant difference in the rate of seropositivity for anti-HBs between the group A and B (53.0% vs. 78.1%, P < 0.001). There was no significant age-adjusted difference in the mean seropositivity rate between the 2 groups (P = 0.058). In addition, the anti-HBs positivity rate was significantly lower in the group A as compared with the group B during infancy (83.1% vs. 92.1%, P < 0.001). A total of 1,106 anti-HBs-positive subjects underwent serologic tests more than twice. Of these, 217 subjects (19.6%) showed anti-HBs disappearance. After booster vaccinations, 87.4% (83/95) achieved seroconversion from seronegative to seropositive. Our results highlight the importance of lifelong protection against HBV and the possible necessity of booster vaccination after adolescent period.

Comparison of seroconversion rates between low-dose intradermal and recommended dose intramuscular hepatitis B vaccination in children

Introduction Massive hepatitis B vaccination is expensive. Re-sults of studies showed that reduced dosage given intradermallyto adults and intramuscularly to children were able to induceseroconversion.Objective To compare the anti-HBs seroconversion (seropositiveand seroprotective) rates between intradermal low-dose of 2 mg(ID-2) and intramuscular recommended dose of 10 mg (IM-10)vaccination against hepatitis B.Methods In a randomized clinical trial, using the hepatitis B plasmavaccine, elementary school children in Tanjung Enim subdistrict,80-168 months of age, were randomly assigned to be given threedoses of either the ID-2 (n=59) or IM-10 (n=64) vaccinations atone month intervals. Seropositive (anti HBs titer &gt;2.1 mIU/l) andseroprotective (anti HBs &gt;10 mIU/l) rates as well as the seroposi-tive and seroprotective geometric mean antibody titers (GMTs) werecompared one month after each inoculation. A p value of &lt;0.1was considered statistically significant.Results One month after the third inoculation, there was no sig-nificant difference in the seropositive rate (95% vs. 89%),seroprotective rate (85% vs. 83%), seropositive GMTs (55.85 mIU/l vs. 61.24mIU/l), and seroprotective GMTs (73.86 mIU/l vs. 72.49mIU/l) between the ID-2 and the IM-10 groups (all with p&gt;0.1)Conclusion Reduced doses of the hepatitis B vaccine given in-tradermally may offer protection against hepatitis B, thus it may beuseful for mass vaccination programs

Antibody response to revaccination among adult non-responders to primary Hepatitis B vaccination in China

About 10% adult failed to develop antibody response after primary hepatitis B vaccination, and revaccination may be an option to improve immune response, but the antibody responses to revaccination in adult non-responders have not been fully examined. Adult non-responders to primary 3-dose hepatitis B vaccination were randomly divided into 2 groups and revaccinated with 20 μg hepatitis B vaccine (HepB) derived from Saccharomyces Cerevisiae (HepB-SC) or 20 μg HepB derived from Chinese hamster ovary cells (HepB-CHO), respectively, at 0-, 1-, 6- month. Seroconversion rate and titer of antibody against hepatitis B surface antigen (anti-HBs) was measured one month after the 1st and 3rd revaccination dose. Anti-HBs seroconversion rates significantly increased from 54.98% [95% confidence interval (CI) 48.60%–61.24%] after the 1st revaccination dose to 89.24% (95% CI: 84.74%–92.79%) after the 3rd revaccination dose (P < 0.001), and the geometric mean titer (GMT) of anti-HBs increased from 12.18mIU/ml (95%CI: 7.81–18.98 mIU/ml) to 208.31 mIU/ml (95% CI: 148.87–291.47 mIU/ml) (P = 0.008).Compared with those with anti-HBs titer <2 mIU/ml after primary vaccination, those with antibody titer ≥2 mIU/ml after primary vaccination had higher seroconversion rate after the 1st dose revaccination (38.36% vs. 78.10%, P < 0.001) and after the 3rd dose of revaccination (84.25% vs. 96.19%, P = 0.003), and had higher antibody titer after the 1st dose of revaccination (3.32mIU/ml vs. 74.21mIU/ml, P < 0.0001) and after the 3rd dose of revaccination (145.73mIU/ml vs. 342.34mIU/ml, P = 0.01). Anti-HBs titer was significantly higher in those revaccinated with HepB-CHO than those revaccinated with HepB-SC after the 3rd dose (131.46 mIU/ml vs. 313.38mIU/ml, P = 0.01). Revaccination on adult HepB non-responders increased the immune response to HepB and may confer further protection against hepatitis B virus infection. If possible, revaccination might be an option to HepB non-responders to secure more protection.

Optimal vaccination program for healthy adults in China

There is still no suitable routine hepatitis B immunization strategy for adults in China. To establish an optimal vaccination schedule for healthy adults, we investigated various schedules in healthy adults. In this randomized 5143 healthy adults received 10 μg hepatitis B vaccine at 0, 1 and 3 months(group A), 0, 1 and 6 months(group B), or 0, 1 and 12 months(group C). Blood samples were collected after 1 month and 12 months after the third dose. The geometric mean titer (GMT), seroconversion rate (levels of anti-HBs ≥10 mIU/mL) and high response rate (levels of anti-HBs ≥100 mIU/mL) were assayed. In our study, 2438 healthy adults finished the full vaccination program and follow-up. The seroconversion/sero-protective rate of groups A–C at one and 12 month after administration of the third vaccine dose was 100%, 99.9% and 97.9% verse 64.9%, 75.7% and 79.0%, respectively. GMT for anti-HBs tested in group A to C within 1 or 12 month after the third vaccination was 213.16, 432.58 and 451.47 mIU/ml verse 22.07, 46.70 and 56.18 mIU/ml, respectively. There were significant differences of seroconversion/sero-protective rate and GMT among the 3 groups (p < 0.01). Given the high anti-HBs seroconversion rate and GMT in all 3 groups, a flexible schedule for Hepatitis B vaccine should be recommended to adults, but 0-1-12 schedule is a better choice.

Efficacy of antigen dosage on the hepatitis B vaccine response in infants born to hepatitis B-uninfected and hepatitis B-infected mothers

ObjectiveTo compare the safety and immunogenicity of two dosages of recombinant hepatitis B (HB) vaccine administered to infants born to HB-uninfected and HB-infected mothers. MethodsA phase III, controlled, single-blinded clinical trial was conducted with 506 healthy newborns. The newborns were assigned to three groups based on maternal levels of HB surface antigen (HBsAg) and HB e antigen (HBeAg): Group A, HBsAg negative; Group B, HBsAg positive and HBeAg negative; and Group C, HBsAg positive and HBeAg positive. Three doses of 10 or 5μg recombinant HB vaccine were randomly administered by 1:1 within 24h after birth, at 1 month and at 6 months. Safety data and pre- and postvaccination blood samples were collected. ResultsA total of 326, 93, and 87 subjects were included in Groups A, B, and C, respectively. Both dosages of HB vaccine were well tolerated by all subjects. The most common injection-site adverse reactions (ARs) and systemic ARs were pain and fever. After 1 month of the third dose, the Group A infants who received the 10μg HB vaccine achieved a higher geometric mean concentration (GMC) of HB surface antibody (anti-HBs) than those who received the 5μg dosage. Maternal anti-HBs serostatus did not influence HB vaccine immunogenicity at either dosage. In contrast, there was no significant difference in the anti-HBs seroconversion rate, GMCs, or estimated vaccine efficacy (EVE) against perinatal transmission between Groups B and C, regardless of dosage. However, the seroconversion rate and EVE of the 5μg HB vaccine was lower in Group C than in Group B. ConclusionsBoth dosages of the HB vaccine were well tolerated and elicited a good immune response in infants of Group A, regardless of the maternal anti-HBs serostatus. EVE did not significantly differ between Groups B and C.Clinicaltrails.gov identifier: NCT02152709

Chronic hepatitis B in children with or without malignancies: a 13-year follow-up.

To evaluate the outcome of chronic hepatitis B (CHB) in children with or without malignancies. Twenty four children (15 boys and 9 girls) with malignancies, followed up by the pediatric gastroenterology outpatient clinic for CHB between January 2000 and December 2013, were enrolled in the study (Group 1). Group 2 was formed with twenty five children (11 girls and 14 boys) diagnosed with CHB without malignancies. The data from the patients' records were compared between the two groups. Hepatitis B e antigen (HBeAg)/antiHBe seroconversion was observed in 3 patients (12.5%) in group 1 and 15 patients (60%) in group 2, with annual seroconversion rates of 1.61% and 16.6%, respectively, and the difference was significant (P<0.01). One patient (6.6%) in Group 1 and 9 patients (53%) in Group 2 showed HBeAg/antiHBe seroconversion after treatment and the difference between the two groups was significant (P<0.06) Loss of hepatitis B surface antigen was observed in one patient in each of group 1 and 2. No clinical, laboratory and imaging findings of liver disease were observed in any of the patients at the end of the study. HBeAg/antiHBe seroconversion rate was lower in patients who had recovered from cancer.

Effect of HLA‐DP and IL28B gene polymorphisms on response to interferon treatment in hepatitis B e‐antigen seropositive chronic hepatitis B patients

The reason why the majority of chronic hepatitis B (CHB) patients do not respond to conventional interferon (IFN)-α or pegylated interferon (PEG IFN) treatment has not been formally demonstrated. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) and response to IFN-α or PEG IFN therapy in Chinese patients with CHB. Four SNPs among the HLA-DPA1, HLA-DPB1 (rs3077 and rs9277535) and IL28B (rs12979860 and rs8099917) regions were genotyped using the MGB-TaqMan SNP genotyping assay in 144 hepatitis B e-antigen (HBeAg) seropositive CHB patients who had received 6-12 months IFN-α or PEG IFN treatment. Patients were classified as responders who achieved any of the four targets: (i) the loss of HBeAg; (ii) anti-HBe seroconversion; (iii) suppression of hepatitis B virus (HBV) DNA level to below 3 log of baseline; and (iv) alanine aminotransferase normalization. By multivariate analysis at 6 months of therapy and 6 months post-therapy, the results showed that rs3077-GG genotype was independently associated with higher HBeAg loss rate and anti-HBe seroconversion rate, and rs9277535-GG genotype was independently associated with decline of HBV DNA level. However, we did not observe the significant association between SNP near IL28B and the response to IFN-α or PEG IFN treatment. This study suggested that HLA-DPA1 and HLA-DPB1 variants were significantly associated with HBeAg loss, anti-HBe seroconversion and HBV DNA level suppression in HBeAg seropositive CHB patients who received IFN-α or PEG IFN treatment.

The effects of different dosage levels of hepatitis B vaccine as booster on anti-HBs-negative children 5–15 y after primary immunization; China, 2009–2010

The changes in lgG antibody levels to hepatitis B surface antigen (HBsAg) and in antibody to HBsAg (anti-HBs) seroconversion rates due to different dosages of hepatitis B vaccine (HepB) were compared in 2106 children. Children who had been previously vaccinated as infants with HepB were revaccinated at 5–15 y of age, after which the antibody titers were determined. After the first booster dose, the anti-HBs seroconversion rate (defined as an anti-HBs ≥10 mIU/ml) with 10 μg of HepB (93.6%) was significantly greater than the rate with 5 µg of HepB (90.3%) (P < 0.05); the anti-HBs seroconversion rate in 10–15-y-old boys vaccinated with 10 μg of HepB (90.9%) was significantly greater than the rate with 5 µg of HepB (84.3%) (P < 0.05). The anti-HBs seroconversion rates after the third booster dose with 5 or 10 μg of HepB were greater than those after the first booster dose (99.6% and 99.7%, vs. 90.3% and 93.6%, P < 0.05); as was the corresponding GMTs (658 ± 4 mIU/ml and 2599 ± 3 mIU/ml, vs. 255 ± 11 mIU/ml and 877 ± 11 mIU/ml [P < 0.05]). The immunization effects of booster vaccination with 3 doses of HepB with 5 or 10 µg are effective; a single booster dose with 10 µg of HepB for 10–15-y-old boys and with 5 or 10 µg of HepB for 5–9 y old boys and for 5–15-y-old girls are effective in generating protective antibody against HBV; however, for anti-HBs-negative children after a single dose of booster, 3 doses are needed.

The effects of booster vaccination on combined hepatitis A and hepatitis B vaccine in both anti-HBs and anti-HAV negative children 5–15 y after hepatitis B vaccine primary immunization

In the present study, we investigated the changes in both anti-HAV lgG and anti-HBs lgG levels and compared the antibody seroconversion rates of different doses of combined hepatitis A and hepatitis B vaccine in children. Children who were vaccinated as infants with Hepatitis B vaccine were revaccinated at 5–15 y of age, then the antibody titers were monitored. Among 283 children, this study found that the anti-HAV seroconversion rates (defined as anti-HAV ≥ 1mIU/ml) after the first and the third dose were 79.9% and 100% respectively; these observed differences were statistically significant (P < 0.05); the corresponding geometric mean titers (GMTs) were 4.72 ± 2.63 mIU/ml and 13.46 ± 1.16 mIU/ml respectively. The anti-HBs seroconversion rates (defined as an anti-HBs ≥ 10 mIU/ml) were 82.3% and 99.0% respectively; these observed differences were statistically significant (P < 0.05); and the corresponding titers were 319.95 ± 5.16 mIU/ml and 418.59 ± 3.89 mIU/ml respectively. After the first booster dose, the difference in anti-HAV seroconversion rate was statistically significant in children aged 5–9 y and 10–15 y (P < 0.05), as was the difference of anti-HBs seroconversion, whereas after the third dose the difference was not statistically significant (P > 0.05). This study demonstrated that the immunization effects of booster vaccination with combined hepatitis A and hepatitis B vaccine is successful for children. A single booster dose is adequate for younger children, while three doses are needed for older children.

Sequential therapy with entecavir and PEG‐INF in patients affected by chronic hepatitis B and high levels of HBV‐DNA with non‐D genotypes

Complete eradication of hepatitis B virus (HBV) is rarely achieved. Treatment options include currently available nucleos(t)ide analogues and pegylated interferon. The aim of our exploratory study was to assess the effectiveness of sequential therapy for chronic hepatitis B (CHB) vs the current standard of care. We evaluated an association with entecavir and pegylated interferon alfa-2a (PEG-IFN) in 20 patients with hepatitis B, high HBV viremia and genotypes A, B, C and E. Patients received entecavir alone for 12 weeks, then entecavir and PEG-IFN for 12 weeks, lastly PEG-IFN alone for 36 weeks. The results were compared with 20 patients (control group) treated in the past with 48 weeks of PEG-IFN monotherapy. Our results show that complete sustained virological response (SVR) and partial SVR were, respectively, 60% and 80% in the study group and 10% and 30% in the control group; anti-HBe seroconversion rate were 76.9% vs 15%, and anti-HBs seroconversion were 20% vs 0%, respectively. We found a correlation among different genotypes and virological and serological outcomes - genotype C has a better virological response, while genotype A had a better serological response, and E genotype had a poor response. These results show that a sequential approach is a promising strategy of treatment in patients with CHB and high viremia in comparison with PEG-IFN monotherapy. The E genotype seems to have the worse rate of response and requires other treatment strategies.

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

ObjectiveTo compare the immune responses of the 10μg and 20μg doses of CHO hepatitis B vaccine on adults. MethodsAdults 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 10μg or the 20μg 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. ResultsThe anti-HBs seroconversion rate was 88.8% (95% CI: 85.4–92.2%) and 95.3% (95% CI: 93.0–97.6%), respectively in 10μg and 20μg group. Geometric mean titers (GMT) were 173.42mIU/ml and 585.51mIU/ml, respectively in 10μg and 20μg groups. Multivariate analysis demonstrated that diabetes, spouse is hepatitis B virus infector, older age and receipt of the 10μg dose were all negatively associated with antibody response (P<.05). Cellular immunity results showed: IL-4 immunity spot numbers in 20μg group was higher than 10μg 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. ConclusionThe humoral immunity and cytokines response among the group that received the 20μg CHO hepatitis B vaccine dose was superior compared to the group that received the 10μg dose. The 20μg dose of CHO hepatitis B vaccine should be prioritized for adult vaccination programs in China.

Study on the cellular and humoral immunity effect of recombinant Chinese hamster ovary cell hepatitis B vaccine in adults

To evaluate the cellular and humoral immunity effect of 10 µg and 20 µg recombinant Chinese hamster ovary (CHO) cell hepatitis B vaccine in adults by randomized double-blind controlled trials. A total of 642 adults aged 18 - 45 years old, non-vaccinated against hepatitis B, and hepatitis B five blood indicators negative were selected as the study subjects. The study subjects were randomly divided into two groups and each group had 321 subjects. The subjects were given 10 µg and 20 µg recombinant CHO hepatitis B vaccination respectively by 0, 1st, 6th month schedule. Blood sample was collected from each study subject one month after the second dose vaccination. The anti-HBs level was detected by Abbott chemiluminescence detection method (I2000) to evaluate humoral immunity status. Of all the study objects, 153 cases were randomly selected by the Excel random function. Their blood samples were collected and Lymphocyte were separated to detect the IL-4 and IFN-γ levels in vitro by enzyme-linked immunospot (ELISPOT) method to evaluate the cellular immunity status. The anti-HBs seroconversion rates in 10 µg and 20 µg dose group were 88.8% (285/321) and 95.3% (306/321) respectively, and 95%CI were 85.4% - 92.2% and 93.0% - 97.6% respectively. The spot forming cell (SFC) of IL-4 of the 20 µg-dose group (x(-) = 20.31) were significantly higher than the 10 µg-dose group (x(-) = 8.19, t = 3.27, P < 0.01). With the increasing of anti-HBs titer, the SFC of IL-4 also went up significantly. There was a positive correlation between SFC of IL-4 and anti-HBs (Spearman correlation coefficient = 0.538, P < 0.0001). No significant difference was found for IFN-γ SFC in two groups (10 µg group: x(-) = 1.49; 20 µg group: x(-) = 0.86; t = 1.83, P > 0.05). The humoral and cellular immune effects of 20 µg recombinant CHO hepatitis B vaccine are better than that of the 10 µg recombinant CHO hepatitis B vaccine.20 µg recombinant CHO hepatitis B vaccine should be chosen as the adult's hepatitis B prevention vaccine.

Study on the immuno-effects and influencing factors of Chinese hamster ovary (CHO) cell hepatitis B vaccine among adults, under different dosages

To evaluate the immuno-effect and related influencing factors on 10 µg and 20 µg Chinese hamster ovary (CHO) cell hepatitis B vaccine, using the randomized double-blind controlled trials in adult population. A total of 642 adults aged 18 - 45 years old, non-vaccinated against hepatitis B, and negative on five blood indicators for hepatitis B, were selected as the study objects from four districts in Beijing. The study objects were randomly divided into two groups, and then accepted 10 µg and 20 µg recombinant CHO hepatitis B vaccination by 0 - 1 - 6 month schedule. Influencing factors were investigated by means of questionnaire. Blood samples were collected one month after the third dose of vaccination. Anti-HBs level was detected by Abott chemiluminescence detection method. For the anti-HBs negative person, fluorescent quantitative PCR method was used to find out if the person had been infected with HBV. Logistic regression analysis was used to find out the influencing factors of anti-HBs seroconversion on every studied subject. The anti-HBs seroconversion rates on 10 µg and 20 µg dose groups were 88.8% (95%CI: 85.4% - 92.2%) and 95.3% (95%CI: 93.0% - 97.6%) respectively. Taking the anti-HBs level < 100 mIU/ml as the low/non-response standard, the low response and non-response rates were 34.3% and 17.4% respectively. The geometric mean titers (GMT) of anti-HBs were 173.42 mIU/ml for the 10 µg dose group and 588.51 mIU/ml for the 20 µg dose group. Data from the Multivariate analysis showed that:diabetes, spouses infected with hepatitis B virus and old age were unfavorable factors for anti-HBs Seroconversion. 20 µg dose of the vaccine was conducive to seroconversion. 20 µg CHO hepatitis B vaccine seemed better than 10 µg CHO hepatitis B vaccine while many factors need to be taken into account for evaluation on hepatitis B vaccines.

Determination of immune memory to hepatitis B vaccination through early booster response in college students

The long-term protection of hepatitis B (HB) vaccination has been debated for years. The purpose here was to evaluate the kinetic changes of antibody to HB surface antigen (anti-HBs) and define immune memory of the HB vaccine among college students who had previously received full neonatal immunization against HB. In all, 127 college students aged 18-23 years born after July 1984 who had completed HB vaccination and were seronegative for all three HB viral markers, including HB surface antigen (HBsAg), antibody to HB core protein (anti-HBc), and anti-HBs, were recruited. They received three doses of HB vaccine at enrollment, 1 month and 6 months after enrollment. Their anti-HBs titers were assayed at enrollment, 7-10 days, 1 month, 6 months, and 7 months following the first dose of HB vaccine. The anti-HBs seroprotective rates for subjects 7-10 days, 1 month, 6 months, and 7 months postvaccination were 20.5%, 75.6%, 94.5%, and 99.2%, respectively. Those who were seroprotective at 7 to 10 days after one dose of HB vaccine booster developed significantly higher levels of anti-HBs at 1 and 6 months than those not developing seroprotective anti-HBs response at an earlier timepoint. At least one-quarter of HB vaccinees have lost their immune memory to the HB vaccine when entering college. Immune memory to HB vaccine was identified by early seroconversion, which was present in only 20% of vaccinees in the present study. To ensure higher than 90% anti-HBs seroconversion rates, at least 2 doses of HB booster vaccines are recommended for at-risk youths who received complete HB vaccinations in neonatal or infant periods but are seronegative for HBsAg, anti-HBs, and anti-HBc in adolescence.