title: [Anti-HBs persistence following primary vaccination with three doses of hepatitis B vaccine among normal and high-responder adults: a 3-year follow-up study].
abstract: 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.
authors.affiliation: Expanded Program Immunization Division, Shandong Provincial Center for Disease Control and Prevention, Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Jinan 250014, China.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lyu
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: B Y
authors.initials: BY
authors.lastname: Yan
authors.forename: J Y
authors.initials: JY
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: L Z
authors.initials: LZ
authors.lastname: Song
authors.forename: S Y
authors.initials: SY
authors.lastname: Chen
authors.forename: L B
authors.initials: LB
authors.lastname: Zhou
authors.forename: X F
authors.initials: XF
authors.lastname: Liang
authors.forename: F Q
authors.initials: FQ
authors.lastname: Cui
authors.forename: F Z
authors.initials: FZ
authors.lastname: Wang
authors.forename: A Q
authors.initials: AQ
authors.lastname: Xu
mesh_terms: D000328:Adult; D000818:Animals; D016466:CHO Cells; D002681:China; D006224:Cricetinae; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000276:immunology* / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000097:blood*; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000145:classification / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008297:Male; D010843:Pichia; D012307:Risk Factors; D012441:Saccharomyces cerevisiae; D000069078:Seroconversion; D014611:Vaccination
chemical_list: D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines