OBJECTIVETo assess the 24-month efficacy after booster vaccination with 3 doses of hepatitis B vaccine among low-response adults in Zhangqiu county of Shandong province.

METHODSA total of 24 237 adults aged 18-49 years old, never received HepB vaccination, without HBV infection history, and had been living at 3 towns of Zhangqiu county in Shandong province for more than half a year in september, 2009, were collected blood samples of 3-5 ml. A total of 11 590 adults who were negative for hepatitis B virus (HBV) surface antigen (HBsAg) , antibody to HBsAg (Anti-HBs) and antibody to HBV core antigen (Anti-HBc), were divided into four groups randomly and were vaccinated following the schedule of 0-1-6 with 20 µg hepatitis B vaccine made by recombinant deoxyribonucleic acid techniques in Saccharomyces cerevisiae (HepB-SC), 20 µg hepatitis B vaccine made by Chinese hamster ovary cell (HepB-CHO), 10 µg HepB-SC and 10 µg hepatitis B vaccine made by recombinant deoxyribonucleic acid techniques in Hansenula Polymorpha (HepB-HP), 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 random sampling. These groups were revaccinated with 3-dose of above-mentioned four kinds of HepB respectively. Blood samples were drawn from 1 month (T1) and 24 month (T24) after the 3 dose revaccination, respectively. Anti-HBs and anti-HBc was detected by Chemiluminescence Microparticle Imunoassay (CMIA).

RESULTSOut of the 8 592 adults who have accepted the primary vaccination of hepatitis B and been collected the blood samples, 1 306 subjects showed low-response. A total of 718 low-response subjects were collected blood samples after T1 and T24 following 3 doses of booster vaccination. The proportion of the four groups was 32.3% (232/718), 25.8% (185/718) , 19.3% (139/718) , 22.6% (162/718) , respectively. The average proportion of anti-HBs ≥ 100 mIU/ml were decreased from 77.58% after T1 to 35.63% after T24 (χ² = 256.87, P < 0.01). The proportion of anti-HBs ≥ 100 mIU/ml in T24 were 38.8% (90/177), 39.5% (73/185), 25.2% (35/139) and 35.8% (58/162) in four groups, respectively. The proportion of anti-HBs>100 mIU/ml in T24 was significantly different among groups (χ² = 8.81, P = 0.032). The average geometric mean concentration (GMC) was significantly reduced from 443.53 mIU/ml after T1 to 48.98 mIU/ml after T24 (F = 439.41, P < 0.01). The GMC was 60.26 (45.71-77.62), 1.29 (38.90-69.18) , 35.48 (25.70-48.98) and 46.77 (33.88-6.07) mIU/ml in four groups, respectively (F = 1.97, P = 0.117) . Compared with vaccinated 20 µg HepB-SC, the proportion of anti-HBs ≥ 100 mIU/ml and GMC was 0.56 (0.35-0.91) and -0.20 (-0.39--0.02) times. The positive of HBsAg was not found and the positive rate of anti-HBc was 2.6% (18/692) in T24.

CONCLUSIONProtective antibody following booster vaccination with three doses of hepatitis B vaccines among low-response adults after 2 years fade faster. Antibody level of anti-HBs in T24 was corrected with the booster vaccine type and age. 20 µgHepB-SC seemed better than 10 µg HepB-SC.

Adult ; Animals ; CHO Cells ; Cricetulus ; Follow-Up Studies ; Hepatitis B ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines ; Hepatitis B virus ; Humans ; Immunization, Secondary ; Pichia ; Vaccination

OBJECTIVETo examine the immune memory status to hepatitis B vaccine among infants with normal or high antibody response to primary vaccination, 5 years after the primary vaccination and the risk factors associated with the immune memory.

METHODSTiters of the antibody against hepatitis B surface antigen (anti-HBs) were detected, five years after the primary vaccination among children who appeared normal or high response to hepatitis B primary vaccination in infancy. Those whose anti-HBs titers were low than protective level (10 mIU/ml) were given a challenge dose of hepatitis B vaccine and titers of anti-HBs were detected 14 days after the challenge. Positive rate and geometric mean titer (GMT) of anti-HBs were calculated. Level of the anti-HBs titers after primary vaccination, at following-up and after the challenge periods were divided into different levels, respectively. Risk factors associated with the levels of anti-HBs titer after the challenge were examined by univariate analysis that and multivariable analysis.

RESULTSAnti-HBs waned to the level below protective standard among 37.98% of the children with normal or high antibody response to hepatitis B primary vaccination; among those children whose anti-HBs were below the protection standard. The seroconversion rate and GMT of anti-HBs after the challenge dose were 98.95% (757/765) and 2 811.69 mIU/ml [95% Confidence Interval (CI) :2 513.55-3 145.19 mIU/ml] , respectively. Titers and levels of anti-HBs after the challenge, appeared an increase with anti-HBs after primary vaccination and the anti-HBs in the following-up (F=5.46, 10.23 respectively; P<0.000 1 for both) periods. Results from the multivariable analysis showed that gender, premature birth and birth weight were factors insignificantly associated with the anti-HBs titers after the dose of challenge, while the anti-HBs levels were independently associated with the levels of anti-HBs titer after the challenge [OR = 1.001 (95%CI: 1.000-1.002) , P<0.001; OR=1.28 (95%CI: 1.81-1.39) , P<0.001]at the following-up periods.

CONCLUSIONSStrong immune memory could be found among those children with normal or high responses to hepatitis B vaccination, 5 years after the primary vaccination. The intensity of immune memory might be associated with the anti-HBs titer after primary vaccination as well as the anti-HBs titers before the challenge dose was given.

Antibody Formation ; Child ; Follow-Up Studies ; Hepatitis B ; prevention & control ; Hepatitis B Antibodies ; isolation & purification ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B Vaccines ; immunology ; Humans ; Immunization ; Immunologic Memory ; Infant ; Risk Factors ; Seroconversion