乙型肝炎疫苗无应答儿童复种五年效果观察

目的评价乙型肝炎（乙肝）疫苗无应答儿童复种远期效果并比较小剂量皮内与常规剂量肌肉复种效果。方法自1999年9月开始,40名经筛检获得的无应答健康儿童随机接受3针肌肉（17人,10μg／针）或皮内（23人,2μg／针）复种,定期采血检测至复种后5年;80名应答儿童不复种,作为同期观察对照。在第5年,评价HBsAg特异性淋巴细胞免疫水平;对抗-HBs阴转者加强1针（5μg）,12—14d评价抗体回忆应答。结果仅1名皮内复种者抗-HBs未达到10IU／L;在第5年,50％的肌肉复种者仍保持着抗-HBs≥10IU／L（尽管该指标显著低于应答对照者的85％）。抗-HBs阴转者（肌肉、皮内复种和应答对照分别为8、18和11人）在加强1针后,除2名皮内复种者外,均产生了强劲的抗体回忆应答（抗．HBs滴度分别平均上升至208、105和549IU／L）;超过70％的无应答儿童外周血单个核细胞可检测到HBsAg特异性白细胞介素（IL）-2和IL-5的分泌。用抗-HBc阳转作为感染指标计算乙肝病毒人年感染率,皮内复种者为8．9％（8／89．9人年）,高于应答对照者的3．6％（12／337．2人年）,而肌肉复种者为4．3％（3／70．2人年）,与应答对照者接近。结论无应答儿童3针肌肉复种效果虽达不到应答儿童初种的水平,但确能发挥重要的免疫保护作用。小剂量皮内复种效果不如相同针次常规剂量肌肉复种。

A five-year observation on efficacy of revaccination in children of non-response to hepatitis B vaccine

OBJECTIVES: To evaluate the long-term efficacy of revaccination in non-responder children to primary hepatitis B (HB) vaccination and to compare the efficacy of low-dose intradermal inoculation to that of routine-dose intramuscular inoculation. METHODS: 40 healthy non-responder children to primary HB vaccination identified by screening were given a three-dose revaccination randomly by intramuscular (n = 17, 10 microg per dose) or intradermal route (n = 23, 2 microg per dose) since September, 1999, and their blood specimens were collected regularly for testing for HB virus markers up to five years. Another 80 responder children to primary HB vaccination were also followed-up as controls without revaccination. By the end of five-year follow-up, HBsAg-specific lymphocyte response was investigated in vitro, and a booster dose (5 microg) was given to those with negative conversion of anti-HBs and their anamnestic responses were evaluated 12-14 days later. RESULTS: Serum anti-HBs did not reach 10 IU/L only in one of 40 non-responder children, who received intradermal revaccination. In the fifth year after revaccination, 50% of the non-responder children who received intramuscular revaccination still maintained anti-HBs of > or = 10 IU/L, though the rate was significantly lower than 85% in controls. Following the booster dose, a robust anamnestic response was developed in all of 8 intramuscular revaccinees and 11 controls but 16 of 18 intradermal revaccinees, who lost anti-HBs of > or = 10 IU/L over time, and geometric mean titers of anti-HBs climbed to 208, 105, and 549 IU/L, respectively. Secretions of HBsAg-specific interleukin-2 and -5 could be detected in peripheral blood mononuclear cell samples of more than 70% of non-responder children. Person-year infection rates of HB virus were 8.9% (8/89.9 person-years) for intradermal revaccinees, significantly higher than 3.6% (12/337.2 person-years) in controls, and 4.3% (3/70.2 person-years) for intramuscular revaccinees, approximating to that of controls, based on positive conversion of anti-HBc. CONCLUSIONS: Three-dose intramuscular revaccination did play an important immune protection for non-responder children to primary HB vaccination, but its efficacy could not reach the level of primary vaccination in responders. Low-dose intradermal inoculation was not as effective as route-dose intramuscular inoculation with the same doses in revaccination for non-responder children to primary HB vaccination.