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[对乙肝疫苗无应答儿童再接种效果的五年观察]

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

作者信息

Zhuang Gui-hua, Yan Hong, Wang Xue-liang, Wu Qian, Wang Li-rong, Gao Hai-yan

机构信息

Department of Epidemiology and Biostatistics, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.

出版信息

Zhonghua Yu Fang Yi Xue Za Zhi. 2006 Jan;40(1):8-12.

PMID:16620590
Abstract

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.

摘要

目的

评估对初次乙肝(HB)疫苗接种无应答儿童进行再接种的长期效果,并比较低剂量皮内接种与常规剂量肌内接种的效果。

方法

自1999年9月起,对通过筛查确定的40名初次HB疫苗接种无应答的健康儿童,随机采用肌内注射(n = 17,每剂10微克)或皮内注射(n = 23,每剂2微克)进行三剂次再接种,并定期采集他们的血液标本检测HB病毒标志物,随访长达五年。另外80名初次HB疫苗接种有应答的儿童作为对照,不进行再接种并进行随访。在五年随访结束时,体外研究HBsAg特异性淋巴细胞反应,对抗-HBs转阴的儿童给予一剂加强剂量(5微克),并在12 - 14天后评估其回忆反应。

结果

40名无应答儿童中仅1名接受皮内再接种的儿童血清抗-HBs未达到10 IU/L。再接种后第五年,接受肌内再接种的无应答儿童中有50%仍维持抗-HBs≥10 IU/L,尽管该比例显著低于对照组的85%。给予加强剂量后,8名肌内再接种者和11名对照者均产生了强烈的回忆反应,但18名皮内再接种者中有16名随着时间推移抗-HBs降至<10 IU/L,其抗-HBs几何平均滴度分别升至208、105和549 IU/L。超过70%的无应答儿童外周血单个核细胞样本中可检测到HBsAg特异性白细胞介素-2和-5的分泌。基于抗-HBc阳转情况,皮内再接种者的HB病毒人年感染率为8.9%(8/89.9人年),显著高于对照组的3.6%(12/337.2人年),肌内再接种者为4.3%(3/70.2人年),接近对照组。

结论

三剂次肌内再接种对初次HB疫苗接种无应答儿童确实起到了重要的免疫保护作用,但其效果未能达到初次接种有应答儿童的水平。对于初次HB疫苗接种无应答儿童,低剂量皮内接种在再接种时不如相同剂量的常规剂量肌内接种有效。

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