Search

This study followed up the immune memory after 3-dose revaccination among infants with non-and low-response following primary hepatitis B (HepB) vaccination. About 120 children without self-booster doses were finally included who had anti-HBs<10 mIU/ml (anti-HBs negative) at the time of follow-up, of whom 86 children completed blood sampling and anti-HBs testing. Before the challenge dose, all 86 children were negative for anti-HBs, and the GMC of anti-HBs was<10 mIU/ml. The seropositive conversion rate of anti-HBs was 100% and the GMC of anti-HBs was 886.11 (95% CI : 678.15-1 157.84) mIU/ml after the challenge dose. Compared with those with GMC<7 mIU/ml before the challenge dose, infants with GMC>7 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95% CI ) was 0.82 (0.18-1.46) ( P =0.012). Compared with those with GMC<1 000 mIU/ml at primary vaccination, infants with GMC≥1 000 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95% CI ) was 0.78 (0.18-1.38)( P =0.012). The results showed a stronger immune memory was found at 9 years after revaccination among infants with non-and low-response to HepB.

Objective: Assess the 10-year Immune persistence and the predictors after primary vaccination hepatitis B vaccine (HepB) among normal and high-responder infants. Methods: A total of 1 838 Infants of 7-12 months old located in Jinan, Weifang, Yantai and Weihai of Shandong Province who were induced normal or high antibody response (anti-HBs titer ≥ 100 mIU/ml) after primary vaccination (three dose with 0-1-6 procedure) with 5 μg recombinant HepB among newborns were included in the study, in 2009. 3 ml of venous blood samples were collected at baseline survey (T 0 ) and antibodies against hepatitis B surface antigen (anti-HBs), antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected using chemiluminescence microparticle immunoassay (CMIA) method. A self-designed questionnaire was used to collect information including the infant's age, sex, birth weight, premature birth, birth number, delivery location and mother's HBV infection status. In 2014 (followed up for 5 years) and in 2019 (followed up for 10 years) (T 1 ), 2 ml of venous blood samples were collected. Anti HBS and anti HBC were detected by CMIA method. Those with anti HBS<10 mIU/ml were detected by CMIA method. Multivariate unconditional logistic and linear regression models were used to analyze the influencing factors of anti-HBs positive rate and geometric mean concentration (GMC) at T 1 . Results: After 10 years follow-up, 73.94% of the subjects (1 359/1 835) finished the follow-up. 51.15% of the subjects, a total of 625 were boys. The positive rate of anti-HBs was 100% at T 0 and decreased to 53.44% (95% CI : 50.59%-56.26%) at T 1 . The average annual decline rate of anti-HBs positive rate from T 0 to T 1 was 6.07%. The GMC of anti-HBs decreased from 607.89 (95% CI : 579.01-642.62) mIU/ml to 16.44 (95% CI : 15.06-18.00) mIU/ml. The average annual decline rate of anti-HBs GMC in 10-year follow-up was 30.30%. Multivariate logistic analysis showed that the positive rate of anti-HBs at T 1 was lower in those who did not vaccinate the first dose in time ( OR =0.25, 95% CI :0.07-0.71). Compared with those with GMC<1 000 mIU/ml at T 0 , those with GMC ≥ 1 000 mIU/ml had a higher positive rate of anti-HBs at T 1 ( OR =2.29, 95% CI :1.76-2.97). Multivariate regression analysis showed that the GMC of anti-HBs at T 1 was lower in those who did not vaccinate the first dose in time (β=-0.50, 95% CI :-1.24-0.24). Compared with those with GMC<1 000 mIU/ml at T 0 , those with GMC ≥ 1 000 mIU/ml had a higher GMC of anti-HBs at T 1 (β=0.81, 95% CI : 0.62-1.05). Conclusion: Anti-HBs GMC decreased in 10 years after primary vaccination of 5 μg recombinant hepatitis B vaccine among normal and high-responders. The anti-HBs persistence was mainly associated with whether the first dose was vaccinated in time and the level of anti-HBs at the end of primary vaccination.

Objective: To evaluate the persistence of HBsAg-specific antibodies eight years after revaccination with hepatitis B vaccine (HepB) among adults who were non-responsive to primary immunization. Methods: From August to September 2009, rural communities in Zhangqiu district of Ji'nan city were selected as the study site. The subject's inclusion criteria were 18 to 49 years old, local resident population, without HBV infection history and HepB vaccination history, and good health status. Antibodies against hepatitis B surface antigen (anti-HBs) were detected in adults following the standard primary vaccination. Those who were non-responders (anti-HBs titer <10 mIU/ml) were revaccinated with three doses of HepB and included in the study. Blood samples were collected from all of them at one month (T 1 ), two years, four years, and eight years after revaccination. The three indexes of anti-HBs, hepatitis B surface antigen (HBsAg), together with antibody against hepatitis B core antigen (anti-HBc), were measured by chemiluminescence microparticle immunoassay (CMIA). Results: The proportion of subjects with anti-HBs titers ≥10 mIU/ml was 85.12% (549/645) at T 1 , 60.60% (283/467) at two years, 55.90% (199/356) at four years and 55.09% (222/403) at eight years after revaccination. The first two years' annual decline rates, three to four years and five to eight years, were 15.62%, 3.96%, and 0.36%. The GMC of anti-HBs was 153.92 mIU/ml at T 1 , 21.43 mIU/ml at two years, 15.02 mIU/ml at four years, and 13.68 mIU/ml at eight years. In the first two years, three to four years and five to eight years, the annual decline rate of GMC was 62.69%,16.28%, and 2.31%, respectively. Multivariable analysis showed that the titer of anti-HBs at T 1 was independently associated with the persistence of anti-HBs at eight years after revaccination. Compared with anti-HBs titer <100 mIU/ml , those whose anti-HBs titers were 100-mIU/ml and ≥1 000 mIU/ml at T 1 had a higher positive rate of anti-HBs ( OR =14.13, P <0.001; OR = 62.91, P <0.001) and a higher probability of anti-HBs titer ( β =1.88, P <0.001; β =3.24, P <0.001) at 8 years after revaccination. Nobody was found seroconversion of HBsAg, and the anti-HBc positive rate was 14.14% (57/403). Conclusions: Following revaccination with three doses of HepB in adults who were non-responsive to primary immunization, anti-HBs titers declined rapidly within the first four years. They then maintained a stable level after the fifth year. More than half still kept anti-HBs protective titer at eight years after revaccination. The immunity persistence was associated with anti-HBs titer at one month after revaccination.

Objective: To estimate the immune memory at 12 years after hepatitis B vaccination and its risk factors among adults. Methods: The study was conducted in 20 villages of Qudi town in Jiyang county, Shandong province, China in 2003. Hepatitis B surface antigen (HBsAg), antibody against HBsAg (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were tested for all healthy residents aged 15-40 years in these villages. Those who had no history of hepatitis B vaccination and were negative for all three indicators were divided into two groups randomly. Hepatitis B vaccine (HepB) was administrated to them on 0-6 month schedule or 0-1-6 month schedule respectively. Blood samples were obtained at one month after the last dose for each receipt and were quantitatively detected for anti-HBs. Finally a total of 629 participants completed HepB vaccination and anti-HBs testing, including 288 of two-dose group and 341 of three-dose group respectively. In 2015, an additional dose of HepB (challenge dose) was administrated to those who were negative for anti-HBs at follow-up (anti-HBs <10 mIU/ml) to evaluate the immune memory. A total of 93 blood samples, including 50 of two-dose group and 43 of three-dose group respectively, were drawn at 14 days after the challenge dose and anti-HBs was quantitatively detected. The anti-HBs geometric mean concentrations (GMCs) after the challenge dose were compared between the two groups. Multivariate linear regression model was built to find the independent risk factors associated with immune memory response (anti-HBs GMC after the challenge dose). Results: The challenge dose of HepB and post-challenge anti-HBs detection were completed among 93 participants. Totally 92 (98.92%, 92/93) participants were found holding immune memory (anti-HBs after the challenge dose was ≥10 mIU/ml). The immune memory positive rates were 100% (50/50) and 97.67% (42/43) in the two-dose group and three-dose group respectively and the corresponding anti-HBs GMC after challenge dose were 2 684.30 (95 %CI : 1 721.71-4 185.08) mIU/ml and 3 527.48 (95 %CI : 2 145.15-5 800.58) mIU/ml ( P= 0.410). The anti-HBs GMC after the challenge dose were 1 908.33 (95 %CI : 1 190.01-3 060.27) mIU/ml, 4 004.20 (95 %CI : 2 257.90-7 101.12) mIU/ml and 8 682.16 (95 %CI : 5 813.94-12 965.36) mIU/ml among the participants whose anti-HBs titer was<4, 4-6 and 7-9 mIU/ml at follow-up, respectively ( P= 0.002). There was no correlation between immune schedule and anti-HBs GMC after the challenge dose; β (95 %CI ) was -0.07 (-0.34-0.20), P= 0.601. Conclusion: The immune memory after primary hepatitis B vaccination lasted for at least 12 years among adults. The immune memory response was independently associated with ant-HBs titer at follow-up, but might be similar between 0-6 month schedule and 0-1-6 month schedule.

Objective: To compare the antibody persistence 5 years after primary immunization with 5 μg and 10 μg recombinant hepatitis B vaccine (HepB) among newborns with normal and high response. Methods: Newborns who completed three doses of 5 μg HepB made by recombinant dexyribonucleic acid technique in Saccharomyces (HepB-SC) or 10 μg HepB made by recombinant dexyribonucleic acid technique in Hansenula polymorpha (HepB-HP) were recruited. Standardized questionnaire was used and blood samples were collected 1-6 months (T(0)) and five years (T(1)) after the third dose respectively. The titer of anti-HBs was detected by chemiluminescence microparticle imunoassay (CMIA). Those who achieved normal or high antibody response (anti-HBs titer ≥100 mIU/ml) were included in the study and the positive rate (≥10 mIU/ml) and titer of anti-HBs at T(1) were compared between 5 μg HepB group and 10 μg HepB group. Multivariable analysis was conducted to identify the independent factors associated with the antibody persistence. Results: The positive rate of anti-HBs at T(1) was 49.92 % (943/1 883) and 75.92 % (1 135/1 495) respectively in 5 μg HepB group and 10μg HepB group, the difference was significant ( χ(2) =237.75, P <0.001). The anti-HBs geometric mean concentrations at T(1) were 10.23 mIU/ml (95 %CI : 9.38-11.16) and 28.91 mIU/ml (95 %CI : 26.65-31.35) in the two groups respectively, the difference was also significant ( F =280.36, P <0.001). Among those whose anti-HBs titer was<10 mIU/ml at T(1), the distributions of anti-HBs titer were significantly different between 5 μg HepB group and 10 μg HepB group ( χ (2)=39.75, P <0.001). The multivariable analysis showed that dosage of HepB was independently associated with both positive rate and titer of anti-HBs at T(1) after excluding the other factors[ P <0.001, OR =1.44 (95 %CI : 1.20-1.73); P <0.001, β =0.27 (95 %CI : 0.14-0.40)]. Conclusion: Five year anti-HBs persistence after primary immunization with 10 μg HepB might be better than that after primary immunization with 5 μg HepB among infants who achieved normal or high anti-HBs response after primary HepB immunization.

Vaccination against the hepatitis B virus (HBV) is extensively used as an effective method to prevent HBV infection. However, nearly 10% of healthy adults fail to produce a protective level of antibodies against the hepatitis B vaccine, and multiple genetic variants are known to affect the immune response to the hepatitis B vaccine. The aim of the present study was to investigate the association between polymorphisms in immunoresponsive gene 1 (IRG1) gene and the immune response to hepatitis B vaccination in a Chinese Han population. Four single nucleotide polymorphisms (SNPs) located in the IRG1 gene were genotyped in 1230 high-responders and 451 non-responders to hepatitis B vaccination. The SNPs rs17470171 and rs17385627 were associated with the immune response to hepatitis B vaccination (P = 0.014 and 0.029, respectively). In addition, the haplotypes G-A-A-A (rs614171-rs17470171-rs9530614-rs17385627, P = 0.0042, OR = 0.68) and A-A (rs17470171-rs17385627, P = 0.0065, OR = 0.72) exerted a protective role in the immune response to hepatitis B vaccination. Allele 'A' of rs17470171 and allele 'A' of rs17385627 show higher levels of expression for the IRG1 gene compared with allele 'C' of rs17470171 and allele 'T' of rs17385627 as demonstrated by luciferase reporter and overexpression assays. In addition, we observed that IRG1 inhibited the HBV life cycle and that IRG1 rs17385627 allele 'A' was more effective than rs17385627 allele 'T' at eliminating HBV in HepG2.2.15 cells. These findings suggest that polymorphisms in the IRG1 gene are associated with the immune response to hepatitis B vaccination. The antiviral effect of IRG1 was confirmed using HBV infection cell models., (© 2017 Wiley Periodicals, Inc.)

Objective: Assess the 4-year antibody against hepatitis B surface antigen (anti-HBs) persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responder infants following primary vaccination. Methods: According to stratified cluster sampling, a total of 4 147 infants were enrolled and primarily vaccinated with 5 μg HepB derived in Saccharomyces Cerevisiae (HepB-SC) at 0-1-6 months schedule from 75 towns of Jinan, Weifang, Yantai, Weihai prefectures, Shandong Province, China in Aug and Sep 2009. Blood samples were collected one to six months after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). 717 infants who appeared low response (10 mU/ml ≤ anti-HBs<100 mU/ml) were revaccinated with 3-dose of HepB. Blood samples were collected from a total of 315 infants one month (T(0)), four years (T(1)) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected by CMIA. Information about their birth, primary vaccination were collected. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple non-conditional logistic regression analysis and multifactor linear regression model analysis, respectively. Results: Among 315 children, 165 (52.38%) were male and 150 (47.62%) were female. The positive rate was 83.81% (264/315) at T(0) and it decreased to 16.51% (149/529) at T(1). The corresponding GMC decreased from 473.15 mU/ml to 17.37 mU/ml. The average annual decreasing rate of positive rate and GMC was 33.38% and 56.23% from T(0) to T(1). Multivariable analysis showed the positive rate and GMC among those whose anti-HBs titer higher at T(0) were significantly higher at T(1). The positive rate at T(1) among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000, ≥1 000 mU/ml at T(0) were significantly higher than those whose anti-HBs titer less than 200 mU/ml. The OR (95 %CI ) of the positive rate was 4.29 (1.03-17.84), 4.53 (1.25-16.47), 4.19 (1.10-15.97) and 9.13 (2.91-28.63), respectively. The GMC at T(1) among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000 mU/ml and those whose anti-HBs titer ≥1 000 mU/ml at T(0) were higher than those whose anti-HBs titer < 200 mU/ml. The b value (95 % CI ) of GMC was 0.84 (0.06-1.62), 1.13 (0.46-1.79), 1.33 (0.65-2.01) and 1.88 (1.33-2.44), respectively. GMC among full-term infants were significantly higher than premature infants at T(1). The b value (95 % CI ) of GMC was 0.86 (0.04-1.68). Conclusion: Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responder infants, but still kept good protection. The anti-HBs persistence after revaccination was associated with anti-HBs level of titer one month after revaccination.

Objective: To assess the 4-year anti-HBs persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responsive adults., Methods: A total of 24 237 healthy adults who had no history of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling method. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 μg HepB-SC and 10 μg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The 892 low-responders were revaccinated with three doses of HepB at 0-1-6 months schedule and the type of HepB was the same as which was used for primary immunization. During the follow-up to low-responders, the following informations were collected: the demographic characteristics (including age, gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases. Blood samples were collected one month (T1) and four years after revaccination and anti-HBs, anti-HBc and HBsAg (if anti-HBs <10 mU/ml) were detected by CMIA. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis respectively. Anti-HBs titer at T1 was grouped according to the level and was considered as the independent variable in the model analysis., Results: A total of 529 participants were identified from 892 low-responders. Among 529 participants, 276 (52.2%) were males and 253 (47.8%) were females. The positive rate was 82.6% (437/529) at T1 and it decreased to 28.2% (149/529) four years after revaccination. The corresponding GMC decreased from 542.06 (95% CI: 466.72-629.56) mU/ml to 27.69 (95% CI: 23.08-33.23) mU/ml. Multivariable analysis showed the positive rate of anti-HBs 4 years after revaccination was independently associated with anti-HBs titer at T1. The positive rate among those whose anti-HBs titer more than 1 000 mU/ml at T1 was significantly higher than those whose anti-HBs titer less than 100 mU/ml. The OR (95%CI) was 39.67 (13.81-114.01). The GMC was associated with HepB type for revaccination and anti-HBs titer at T1. The GMC among those revaccinated 20 μg HepB was significantly higher than those revaccinated 20 μg HepB-CHO, 10 μg HepB-SC and 10 μg HepB-HP. The b (95% CI) was -0.40 (-0.78--0.02), -0.57 (-1.01- -0.15) and -0.63 (-1.03- -0.23), respectively. The GMC among those whose anti-HBs titer 100-999 mU/ml and those whose anti-HBs titer ≥1 000 mU/ml at T1 were higher than those whose anti-HBs titer <100 mU/ml. The b (95% CI) was 0.93 (0.53-1.33) and 3.31 (2.88-3.73) respectively., Conclusion: Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responsive adults, but still kept good protecion. The anti-HBs persistence after revaccination was associated with HepB type for revaccination and anti-HBs level of titer one month after revaccination.

With the effective control of hepatitis B infection among children, the adults especial the young ones become the main population for new hepatitis B virus infection. Now the adults receive hepatitis B vaccination voluntarily and at their own expense in China and the coverage is low. The high immunogenicity of hepatitis B vaccine has been proven among healthy adults. Although the safety of hepatitis B vaccination has been documented among high-risk population such as HIV-infected people, injecting drug users and patients with chronic hepatitis disease, their antibody seroconversion rate after hepatitis B vaccination is lower than the healthy adults. Hepatitis B vaccination is recommended to population at high risk officially in many countries and some effects have been achieved. It is urgent to improve the strategy of hepatitis B vaccination among adults to fasten the control of hepatitis B in China, along with the researches about the long-term efficacy of hepatitis B vaccine among adults, the immunogenicity of hepatitis B vaccination among high-risk adults and the economical evaluation about different adult immunization strategy of hepatitis B.

Objective: To explore anti-HBs persistence four years after revaccination with hepatitis B vaccine (HepB) among adults who were non-responsive to HepB primary immunization., Methods: A total of 24 237 healthy adults who had no history of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and aged 18-49 years were selected from 79 villages of Zhangqiu County, Shandong Province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-1-6months schedule: 20 μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 μg HepB-SC and 10 μg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The non-responders were followed up and their basic information and the histories of hepatitis B infection, HepB vaccination, smoking and drinking were investigated. Then they were revaccinated with three doses of HepB with the same schedule as the primary immunization. Blood samples were collected from all of them one month (T1), two years and four years after revaccination and anti-HBs, anti-HBc and HBsAg were detected by CMIA. A total of 356 participants were followed up from 645 low-responders four years after revaccination, and the ratio was 55.2%. The risk factors associated with the positive rate and geometric mean concentration (GMC) of anti-HBs after four years of revaccination were analyzed using multivariate unconditional logistic regression model and multivariate linear regression model, respectively., Results: Among 356 participants, 172 (48.3%) were males and 184 (51.7%) were females. The anti-HBs positive rate was 90.4% (322 cases) at T1 and was 55.9% (199 cases) four years after revaccination. The GMC of anti-HBs was 240.5 (95% CI: 186.4-310.4)mU/ml at T1 and decreased to 15.0 (95%CI: 12.2-18.5) mU/ml four years after revaccination. The average annual decreasing rate of GMC was 50.63% from one month after revaccination to four years after revaccination. The corresponding rate was 64.89% in the first two years, which was 2.12 times the rate in the latter two years (30.57%). When compared with those whose anti-HBs titer was less than 99 mU/ml at T1, the significantly higher anti-HBs four years after revaccination was observed in those whose anti-HBs titer at T1 was 100-999 mU/ml and those whose anti-HBs titer at T1 was ≥1 000 mU/ml. The OR (95%CI) was 7.14 (3.90-13.05) and 28.40 (13.16-61.30) respectively. When compared with those whose anti-HBs titer was ≤99 mU/ml at T1, the GMC of anti-HBs four years after revaccination was also significantly higher among those whose anti-HBs titer at T1 was 100-999 mU/ml and those whose anti-HBs titer at T1 was ≥1 000 mU/ml. The b (95%CI) was 1.66 (1.26-2.05) and 3.16 (2.72-3.60), respectively., Conclusion: The positive rate and GMC of anti-HBs decreased four years after revaccination among non-responsive adults, but still kept anti-HBs above protective level. The immunity durability after revaccination is mainly associated with anti-HBs titer one month after revaccination.

Objective: To assess the 3-year anti-HBs persistence after primary vaccination with three-dose of hepatitis B vaccine (HepB) among normal and high-responder adults., Methods: A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in local areas for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling method. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 μg HepB-SC and 10 μg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). During the follow-up to normal and high-responders, the following information was collected: the demographic characteristic (including age and gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases. Blood samples were collected one month (T1) and three years after primary vaccination (T2) and anti-HBs, anti-HBc and HBsAg (if anti-HBs<10 mU/ml) were detected by CMIA. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis, respectively., Results: A total of 4 677 normal and high-responders were identified. Among 4 677 participants, 2 014 (43.06%) were males and 2 663 (56.94%) were females. The positive rate was 100% at T1 and it decreased to 80.99% (3 788/4 677) three years after vaccination. The corresponding GMC was decreased from 1 413.48 (95%CI: 1 358.86-1 470.30) mU/ml to 60.33 (95%CI: 56.97-63.90) mU/ml. When comparing with those vaccinated 20 μg HepB-CHO, the significantly lower positive rate of anti-HBs three years after vaccination was observed in those vaccinated 20 μg HepB-SC, 10 μg HepB-SC and 10 μg HepB-HP. The OR (95%CI) was 0.65 (0.50-0.84), 0.52 (0.41-0.67) and 0.31 (0.28-0.45), respectively. The GMC of anti-HBs was also significantly lower among those vaccinated 20 μg HepB-SC, 10 μg HepB-SC and 10 μg HepB-HP. The b (95%CI) was -0.33 (-0.47- -0.20), -0.41 (-0.55- -0.28) and -0.78 (-0.92- -0.65), respectively. The GMC of anti-HBs in those aged 30-39 years old and 40-49 years old were lower than that in 18-29 years. The b (95%CI) was -0.31 (-0.47- -0.15) and -0.24 (-0.39- -0.09), respectively. When comparing with those whose anti-HBs titer was less than 999 mU/ml at T1, the significantly higher positive rate of anti-HBs three years after vaccination was observed in those whose anti-HBs titer was 1 000-1 999 mU/ml, those whose anti-HBs titer was 2 000-9 999 mU/ml and those whose anti-HBs titer was ≥10 000 mU/ml. The OR (95%CI) was 4.97 (3.80-6.49), 7.87 (16.19-10.01) and 9.67 (6.47-14.44), respectively. When comparing with those whose anti-HBs titer was ≤999 mU/ml at T1, the GMC of anti-HBs three years after vaccination was also significantly higher among those whose anti-HBs titer at T1 was 1 000-1 999 mU/ml, those whose anti-HBs titer at T1 was 2 000-2 999 mU/ml and those whose anti-HBs titer at T1 was ≥10 000 mU/ml. The b (95%CI) was 1.00 (0.87-1.14), 1.85 (1.74-1.97) and 3.28 (3.12-3.44), respectively. Four subjects showed HBsAg seroconversion and anti-HBc conversion rate was 4.68% at T2., Conclusions: Anti-HBs GMC decreased rapidly three years after primary vaccination among normal and high-responder adults, while the positive rate of anti-HBs still kept at a high level. The anti-HBs persistence after primary vaccination was associated with HepB type, age and GMC of anti-HBs one month after vaccination.

Objective: To evaluate the 5-year antibody persistence and the risk factors associated with the persistence after primary vaccination of hepatitis B vaccine (HepB) among normal or high-response adults., Methods: A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages in north of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 μg HepB-SC and 10 μg HepB derived in Hansenula polymorpha (HepB-HP). The normal and high-responder was followed up and their demographic characteristic (including age, gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases were investigated. Blood samples were collected one month (T1) and five years (T2) and anti-HBs, anti-HBc and HBsAg (if anti-HBs<10 mU/ml) were detected by CMIA. A total of 1 902 participants were followed up and the risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis, respectively., Results: Among 1 902 adults, 824 (43.32%) were male and 1 078 (56.68%) were female. The anti-HBs positive rate was 100% at T1 and it decreased to 73.29% (1 394 cases) at T2. The corresponding GMC was decreased from 1 527.15 (95%CI: 1 437.84-1 622.01) mU/ml at T1 to 35.07 (95%CI: 32.20-38.19) mU/ml at T2. When comparing with those vaccinated 20 μg HepB-SC, the significantly lower positive rate at T2 was observed in those vaccinated 10 μg HepB-SC group and 10 μg HepB-HP group. The OR (95% CI) was 0.41 (0.28-0.61) and 0.27 (0.18-0.39), respectively. The GMC of anti-HBs was also significantly lower among those vaccinated 10 μg HepB-SC and 10 μg HepB-HP. The b (95%CI) was -0.20 (-0.28- -0.12) and -0.36 (-0.44- -0.29) , respectively. When comparing with those occasionally drinking, the significantly lower positive rate at T2 was observed in those regular drinking. The OR(95%CI) was 0.51(0.30-0.87). The GMC of anti-HBs in age group of 18-29 was significantly higher than those in 40-49 age group; the b (95%CI) was -0.10(-0.18- -0.01). When comparing with those whose anti-HBs titer was less than 999 mU/ml at T1, the significantly higher positive rate of anti-HBs at T2 was observed in those whose anti-HBs titer was 1 000-1 999 mU/ml, those whose anti-HBs titer was 2 000-2 999 mU/ml and those whose anti-HBs titer was ≥10 000 mU/ml. The OR (95%CI) was 10.11 (6.90-14.82), 20.42 (13.98-29.82) and 54.58 (22.08-134.92), respectively. When comparing with those whose anti-HBs titer was ≤999 mU/ml at T1, the GMC of anti-HBs at T2 was also significantly higher among those whose anti-HBs titer at T1 was 1 000-1 999 mU/ml, those whose anti-HBs titer at T1 was 2 000-2 999 mU/ml and those whose anti-HBs titer at T1 was ≥10 000 mU/ml. The b (95%CI) was 0.55 (0.47-0.62), 0.94 (0.88-1.00) and 1.63 (1.54-1.72), respectively. Nobody was found positive to HBsAg at T2 and the conversion rate of anti-HBc was 3.89% (74/1 902) at T2., Conclusion: Anti-HBs GMC decreased rapidly at T2 among normal and high-responder adults, while the positive rate of anti-HBs still kept at a high level. The antibody persistence among normal and high-responder adults at T2 was associated with HepB type, age, history of drinking and GMC of anti-HBs at T1.

Objective: To evaluate and compare the antibody to hepatitis B virus (HBV) surface antigen (anti-HBs) response and the influent factors of revaccination of 4 kinds of hepatitis B vaccine (HepB) among firstly low-response adults., Methods: A total of 11 590 adults who were 18 - 49 years old, never received HepB vaccination, without HBV infection history, HBs-Ag negative, and had been living at 3 towns of Zhangqiu county in Shandong province Ji'nan city for more than half a year, were selected in the study in July, 2009. Self-designed questionnaire was used to select the basic information of the subjects. The subjects were divided into 4 groups by cluster sampling, and were vaccinated according to the "0-1-6" immune procedure with 10 µg HepB made by recombinant deoxyribonucleic acid techniques in Saccharomyces Cerevisiae (HepB-SC), 10 µg HepB made by recombinant deoxyribonucleic acid techniques in Hansenula Polymorpha (HepB-HP), 20 µg HepB-SC and 20 µg HepB made by recombinant deoxyribonucleic acid techniques in Chinese hamster ovary cell (HepB-CHO), 3 doses respectively. The adults who were low-response to the primary hepatitis B vaccination (10 mU/ml ≤ anti-HBs < 100 mU/ml) were divided into four groups by cluster sampling. These groups were revaccinated with one-dose of above-mentioned four kinds of HepB respectively. Blood samples were drawn from each person one month after the revaccination. Anti-HBs was detected by chemiluminescence microparticle immunoassay and compared by the vaccine type. The influence factors about antibody response were also analyzed., Results: Out of the 11 590 subjects, 8592 adults had accepted the primary vaccination of hepatitis B and been collected the blood samples; among whom, 1306 subjects showed low-response, at the rate of 15.20%. A total of 1034 low-response subjects accepted secondary strengthened vaccination and were collected blood samples; 55.13% of them showed anti-HBs seroconversion (anti-HBs ≥ 100 mU/ml); while the seroconversion rate in each group was 44.54% (106/238) in 10 µg HepB-SC group, 57.14% (156/273) in 10 µg HepB-HP group, 56.08% (143/255) in 20 µg HepB-SC group and 61.57% (165/268) in 20 µg HepB-CHO group, respectively. There was significant difference among the groups (χ² = 17.14, P < 0.01). The rates of anti-HBs seroconversion were significantly higher in 10 µg HepB-HP and 20 µg HepB-CHO groups than it in 10 µg HepB-SC group (χ² were 8.09 and 14.70 respectively, P < 0.01). The geometric mean concentration (GMC) of anti-HBs was 178.24 mU/ml among the low-responders after one dose of revaccination. The GMC was 109.77, 243.50, 144.98 and 242.83 mU/ml in 10 µg HepB-SC group, 10 µg HepB-HP group, 20 µg HepB-SC group and 20 µg HepB-CHO group, respectively. There was significant difference among groups (F = 9.52, P < 0.01)., Conclusion: Anti-HBs response could be strengthened effectively after one-dose of HepB revaccination among the low-response adults. Many factors like the vaccine types could effect the immune effects to HepB. A better response could be achieved if the 20 µg HepB-CHO or 10 µg HepB-HP was used for revaccination.

Objective: To compare the antibody response induced by primary immunization with 5 µg and 10 µg hepatitis B vaccine made by recombinant DNA techniques among the newborns., Methods: Healthy infants who had completed primary immunization with 5 µg hepatitis B vaccine made by recombinant dexyribonucleic acid techniques in Saccharomyces (Hep-SC) or 10 µg hepatitis B vaccine made by recombinant dexyribonucleic acid techniques in Hansenula polymorpha (HepB-HP) were included in the study. Kids under study were 7-12 months of age and had been on 0-1-6 schedule. Standardized questionnaire was used and blood samples were collected. The titer of antibody to hepatitis B surface antigen (anti-HBs) was detected by Chemiluminescence Microparticle Imunoassay (CMIA). If anti-HBs happened to be under 10 mIU/ml, HBV DNA was further detected by nested-PCR to distinguish occult hepatitis B virus infection. Sero-conversion rate and titer of anti-HBs were compared between the two kinds of hepatitis B vaccines. Multivariate analysis was used to find the relationship between the kind of hepatitis B vaccine as well as the antibody response after debugging the other influencing factors including month-age, gender, birth-weight, premature birth and mother's HBsAg status., Results: 8947 infants vaccinated with 5 µg HepB-SC and 4576 infants vaccinated with 10 µg HepB-HP were investigated. In the 5 µg group, the rates of non-, low-, normal- and high-response were 1.88%, 15.18%, 61.42% and 21.52% respectively. In the 10 µg group, the corresponding rates were 0.15%, 2.16%, 29.42% and 68.26% respectively. The non-, low-, normal-response rates were all higher in 5 µg group than in 10 µg group (P<0.01), while the high-response rate was much higher in 10 µg group than in 5 µg group (P<0.01). The geometric mean concentration (GMC) of anti-HBs were 354.81 mIU/ml (95%CI: 338.84-363.08 mIU/ml) and 1778.28 mIU/ml (95%CI: 1698.24-1819.70 mIU/ml) in the 5 µg group and 10 µg group respectively. The GMC was statistically higher in the 10 µg group than in the 5 µg group (P<0.001). The sero-conversion rate and GMC were significantly different between the two groups even after debugging the other influencing factors., Conclusion: Better anti-HBs response could be achieved by primary immunization with 10 µg HepB-HP than with 5 µg HepB-SC among newborns.

Objective: To compare the antibody response between preterm and full-term infants after primary immunization of hepatitis B vaccine (HepB)., Methods: Infants who were aged 7 - 12 months and had completed primary immunization with 5 µg HepB made by recombinant deoxyribonucleic acid techniques in saccharomyces cerevisiae (HepB-SC) or 10 µg HepB made by recombinant deoxyribonucleic acid techniques in Hansenula polymorpha (HepB-HP) on 0-1-6 schedule were investigated in four provinces (municipality) including Beijing, Shandong, Jiangsu and Guangxi of China. Among them, all preterm infants were selected to form the preterm group and the 1:1 matching full-term infants with the same month-age, gender and residence were randomly selected to form the full-term group. Their HepB history was determined by immunization certificate and all of their parents were interviewed with standard questionnaire to get their birth information. Blood samples were obtained from all anticipants and were tested for Anti-HBs by chemiluminescence microparticle immuno-assay (CMIA)., Results: Total anticipants were 648 pairs of infants. The rates of non-response, low-response, normal-response and high-response after the primary immunization were 1.39%, 8.64%, 45.83% and 44.14% in the preterm group, respectively. The corresponding rates were 1.08%, 9.26%, 44.91% and 44.75% in the full-term group. The above four rates did not show significant differences between the two groups (P > 0.05). The geometric mean concentrations (GMC) of anti-HBs in the pre-term and full-term group were 755.14 and 799.47 mIU/ml respectively. There was no significantly difference in the GMCs between the two groups (P > 0.05). Results from multivariable conditional logistic analysis showed that preterm was not an influencing factor to the antibody response after HepB primary immunization among newborns even after debugging the other influencing factors., Conclusion: The antibody response after HepB primary immunization were similar among the preterm and full-term infants. The preterm newborns could be immunized under the same HepB immunization strategy.

Vaccination against hepatitis B virus is an effective and routine practice that can prevent infection. However, vaccine-induced immunity to hepatitis B varies among individuals. CD4(+) T helper cells, which play an important role in both cellular and humoral immunity, are involved in the immune response elicited by vaccination. Polymorphisms in the genes involved in stimulating the activation and proliferation of CD4(+) T helper cells may influence the immune response to hepatitis B vaccination. In the first stage of the present study, a total of 111 single nucleotide polymorphisms (SNPs) in 17 genes were analyzed, using the iPLEX MassARRAY system, among 214 high responders and 107 low responders to hepatitis B vaccination. Three SNPs (rs12133337 and rs10918706 in CD3Z, rs10912564 in OX40L) were associated significantly with the immune response to hepatitis B vaccination (P = 0.008, 0.041, and 0.019, respectively). The three SNPs were analyzed further with the TaqMan-MGB or TaqMan-BHQ probe-based real-time polymerase chain reaction in another independent population, which included 1090 high responders and 636 low responders. The minor allele 'C' of rs12133337 continued to show an association with a lower response to hepatitis B vaccination (P = 0.033, odds radio = 1.28, 95% confidence interval = 1.01-1.61). Furthermore, in the stratified analysis for both the first and second populations, the association of the minor allele 'C' of rs12133337 with a lower response to hepatitis B vaccination was more prominent after individuals who were overweight or obese (body mass index ≥25 kg/m(2)) were excluded (1(st) stage: P = 0.003, 2(nd) stage: P = 0.002, P-combined = 9.47e-5). These findings suggest that the rs12133337 polymorphism in the CD3Z gene might affect the immune response to hepatitis B vaccination, and that a lower BMI might increase the contribution of the polymorphism to immunity to hepatitis B vaccination.

Objective: To reveal the hepatitis B vaccine (HepB) coverage in the population of 1-59 years old in Shandong province and provide evidence for improving the strategy for hepatitis B control., Methods: A cross-section survey was conducted among the population aged 1-59 year-old in Shandong province in 2006. The study population was selected by multi-stage randomly sampling method and HepB immunization history was obtained by immunization record (for children 1-14 years old) or recall. Weighted coverage rates were calculated., Results: The weighted complete HepB coverage in the population 1-59 years old was [27.07%95% Confidence Internal (CI) 22.56%-31.59%] in Shandong province and was 99.66% (95% CI 99.72-100.00%), 89.95% (95% CI 87.69%-92.20%) and 13.21% (95% CI 7.78%-18.65%) in the age group of 1-4 years old, 5-14 years old and 15-59 years old, respectively. The complete HepB coverage varied significantly in the age groups (P < 0.05). No differences were found between the males and females, the rural and urban inhabitants, and among the population living in the eastern, western and central areas (P > 0.05). The weighted timely birth-dose HepB coverage was 65.41% (95% CI 55.56%-75.25%) in the children 1 to 14 years of age, which declined with age and reached the highest level in the children aged 1 year (93.07%; 95% CI 88.43%-97.70%)., Conclusions: A HepB catch-up campaign should be conducted in the elder children in Shandong province and further efforts should be made to improve HepB coverage among the high risk population for enhancement of hepatitis B control.