| Hepatitis B virus (HBV) infection is the leading cause of illness in China which is related to liver cancer or cirrhosis. Qidong area in Jiangsu Province is one of the areas in China with a high prevalence of HBV infection and hepatocellular carcinoma. With the help and support of World Health Organization (WHO) and Ministry of Health of the People’s Republic of China, a large-scale cluster-randomized clinical trial of neonatal HB vaccination was established in this area during1980s, in order to prevent and control chronic hepatitis B infection among children and young adults (midpoint of the study),as well as cirrhosis with hepatic dysfunction and HCC (endpoint of the study). Since the neonatal vaccinees have grown to young adults, presence of immune memory and immunity against HBV infection in adults needs to be clarified. From a cohort of806individuals who received plasma-derive Hep-B-Vax as neonates and consecutively followed at ages5,10and20years, with HBsAg(-) at their age2-5,404twenty-four-year-old adults were sampled in2009for booster test. The results of detecting HBV infection biomarkers showed that, among them4(1%) were found to be HBsAg(+),27(6.7%) were HBsAg(-) anti-HBc(+),121(30.2%) were HBsAg(-) anti-HBc(-) anti-HBs(+), and252(62.4%) were HBsAg(-) anti-HBc(-) anti-HBs(-). Of them,141subjects with HBsAg(-) anti-HBc(-) were boosted with10-μg recombinant HBV vaccine on day-0and1-month. Levels of anti-HBs were determined pre-booster, in day-10-12,1-month and6-month post-booster. The conversion rates of anti-HBs≥10mIU/ml on D10-12and1-month post-booster were71.4%(45/63) and87.3%(55/63)respectively in the vaccinees who were anti-HBs(+) at age5, higher than in those who were anti-HBs(-) at age5,57.5%(23/40) and80.0%(32/40) respectively, but no statistically significant. After the second dose of booster, all subjects with anti-HBs(+) at age5had anti-HBs>500mIU/ml. However,6/40subjects with anti-HBs(-) at age5had anti-HBs<10mIU/ml, geometric mean concentration was3.6(95%CI2.0-7.7). Meanwhile, according to the level of anti-HBs IgG pre-boost and post-boost,141subjects were divided into3groups. Anti-HBs IgM was determined by using indirect ELISA method established in our own labratory. All of the subjects in the3groups showed positive, the IgM relative levels among them showed no statistically significant. Of the subjects received booster,44subjects were determined the presence of T cell immulnity on D10-12,41(93.2%) had HBsAg-specific T cells detectable, including7/10subjects whose anti-HBs were<10mIU/ml10-12days post-booster, and39(88.6%) had HBeAg-specific T cells detectable. In addition, HBV DNA were quantified among27HBsAg(-)anti-HBc(+) subjects by using real time PCR, and S gene were amplified by using nested PCR. Sequences of S gene were analyzed by using MEGA4.0. Among27vaccinees,19had detectable serum HBV DNA, and an "a" epitope mutation was found in1/5HBV isolates. One subject who was anti-HBc(+) at age20converted into HBsAg(+)4years later.In conclusion, the HBsAg-positive rate of children decreased significantly after neonatal HB vaccination. The persistent immunity against chronic HBV infection was present among adults who had responded well to the vaccine at early age, however, subjects who failed to respond or responded weakly to the vaccine might not be fully protected. Since the neonatal HB vaccinees grown up to adults, cellular immune responses to HBV infection were available no matter anti-HBs were positive or not. Low level of virus could be detected in most of the vaccinees with single anti-HBc(+), without any mutation in "a" determinant. |
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