The immunogenicity in healthy infants and efficiency to prevent mother to child transmission of Hepatitis B virus of a 10µg recombinant yeast-derived Hepatitis B vaccine (Hep-KSC).

BACKGROUND AND AIMS: To evaluate immunogenicity and efficacy of a 10µg recombinant Saccharomyces cerevisiae-derived hepatitis B vaccine (Kangtai Biological Products Co. Ltd, Shenzhen, China) (Hep-KSC) in newborns. METHODS: Overall 1197 infants born to mothers negative for HBV markers (NM group) and 534 born to HBsAg-positive mothers (PM Group) were enrolled. Infants in NM group were given 10µg Hep-KSC, 10µg Engerix-B or 5µg Hep-KSC and those in PM group received 10µg Hep-KSC or 10µg Engerix-B at 0, 1 and 6 months, with an additional 200IU HBIG at birth for the latter. RESULTS: For NM Group, 10µg Hep-KSC paralleled 10µg Engerix-B but outperformed 5µg Hep-KSC regarding seroprotective rate (95.06% vs 94.83% vs 89.67%, p=0.0077) and anti-HBs geometric mean concentration (GMC) (798.87mIU/ml vs 790.16mIU/ml vs 242.04mIU/ml, p<0.0001) at 7 months. The proportion of infants with anti-HBs greater than 1000mIU/ml was higher in 10µg Hep-KSC than 5µg Hep-KSC group (45.77% vs 11.93%, p<0.0001) at 7 and 12 months. For PM Group, the HBsAg positivity rate in 10µg Hep-KSC and 10µg Engerix-B group was 1.60% and 4.27% at 7 months, respectively. In 10µg Hep-KSC group, 93.61% and 91.29% achieved seroprotection at 7 and 12 months, respectively, and correspondingly 90.24% and 86.96% in 10µg Engerix-B group. The anti-HBs GMC was comparable between 10µg Hep-KSC and 10µg Engerix-B group at 7 and 12 months (575.31mIU/ml vs 559.64mIU/ml; 265.79mIU/ml vs 264.48mIU/ml). CONCLUSIONS: 10µg Hep-KSC might be appropriate for neonatal immunization with good immunogenicity and efficacy, especially for infants born to HBsAg-positive mothers.

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.

A predictive value of quantitative HBsAg for serum HBV DNA level among HBeAg-positive pregnant women.

BACKGROUND: The high maternal HBV DNA level is the most important factor contributing to HBV perinatal transmission. This study is to explore whether HBsAg can be used as a surrogate marker of serum HBV DNA for HBsAg-positive pregnant women. METHODS: A total of 975 HBsAg-positive pregnant women and their infants were enrolled in this study. All infants received three doses of a yeast-derived recombinant Hepatitis B vaccine at 0, 1 and 6 months. They were also given Hepatitis B immunoglobulin (HBIG) at birth. HBsAg and HBeAg were determined using Abbott Architect assays while serum HBV DNA level was detected by the Abbott Real Time HBV DNA assay. RESULTS: Of the 975 subjects, 367 (37.6%) were HBeAg-positive and 608 (62.4%) were HBeAg-negative. Among the HBeAg-positive group, the samples with HBV DNA levels of ≥7.0 logIU/mL were 76.6% (281/367), and it was only 0.7% (4/608) for the HBeAg-negative group. HBV DNA level was positively correlated with HBsAg in HBeAg-positive group (r=0.786, p<0.001) but not in HBeAg-negative group (r=0.022, p=0.593). Among HBeAg-positive group, the area under the receiver-operator curve (ROC) of HBsAg titer for high HBV DNA level (≥7.0 logIU/mL) was 0.961 (95% CI, 0.940-0.983, p<0.001). The optimum cut-off point HBsAg titer above 4.1 logIU/mL had a sensitivity of 85.1%, specificity of 96.5%, and accuracy of 87.5% to predict HBV DNA levels of ≥7.0 logIU/mL. Of 367 infants born to mothers with HBeAg-positive, perinatal transmission was detected in 24 infants (6.5%, 24/367). Their mothers all had serum HBV DNA levels of ≥7.0 logIU/mL, 23 (95.8%) had HBsAg titers of ≥4.1 logIU/mL and the other mother had HBsAg titer of 3.9 logIU/mL. Of 608 infants born to mothers with HBeAg-negative, only one (0.2%, 1/608) became HBsAg-positive at the age of 7 months, and the mother of the infant had serum HBV DNA level of 3.4 logIU/mL and HBsAg titer of 1.8 logIU/mL, respectively. CONCLUSION: Serum HBsAg titer may be used as a surrogate marker of serum HBV DNA for HBeAg-positive pregnant women.

A type-specific nested PCR assay established and applied for investigation of HBV genotype and subgenotype in Chinese patients with chronic HBV infection.

BACKGROUND: Many studies have suggested that hepatitis B virus (HBV) genotypes show not only geographical distribution and race specificity, but also are associated with disease progression and response to interferon treatment. The objective of this study was to develop a nested polymerase chain reaction (nPCR) assay for genotypes A-D and subgenotypes B1, B2, C1 and C2 of hepatitis B virus (HBV) and to investigate the distribution characteristics of HBV genotypes/subgenotype in China. METHODS: After redesigning the primers and optimizing the reaction conditions using common Taq polymerase, the sensitivity, specificity and reproducibility of the method were evaluated using plasmids and serum samples. In total, 642 serum samples from patients with chronic HBV infection were applied to investigate the distribution of HBV genotype and subgenotype in China. RESULTS: The genotype and subgenotype could be identified when the HBV DNA load of a sample was ≥10(2.3) IU/mL. For the 639 successfully genotyped samples, the sequencing results of 130 randomly selected samples (20.3%, 130/639) were consistent with those of the nPCR method. The present study showed that HBV genotype B (11.2%, 72/642), C (68.2%, 438/642) and D (7.2%, 46/642) were circulating in China, while genotype C was the dominant strain except for western region where genotype D was the prevalent strain. The main subgenotypes of genotypes B and C were B2 (87.5%, 63/72) and C2 (92.9%, 407/438), respectively. CONCLUSIONS: The low-cost nPCR method would be a useful tool for clinical and epidemiological investigation in the regions where genotypes A-D are predominant.