Wang Yuting, Chen Taoyang, Lu Ling-Ling, Wang Minjie, Wang Dongmei, Yao Hongyu, Fan Chunsun, Qi Jun, Zhang Yawei, Qu Chunfeng
Department of Immunology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Qidong Liver Cancer Institute & Qidong People's Hospital, Qidong, Jiangsu Province 226200, China.
Vaccine. 2017 Feb 15;35(7):1064-1070. doi: 10.1016/j.vaccine.2016.12.062. Epub 2017 Jan 6.
Neutralizing antibodies (anti-HBs) after immunization with hepatitis B virus (HBV) vaccines against HBV surface antigen (HBsAg) wane after 10-15years. We analyzed the effect of an adolescent booster given to vaccination-protected children born to mothers with different HBsAg-carrying status against HBV infection in their mature adulthood.
A total of 9793 individuals, who were HBsAg-negative at childhood (baseline) and donated blood samples, both during childhood and adulthood, from the vaccination group in "Qidong Hepatitis B Intervention Study", were enrolled. Among them 7414 received a one-dose, 10μg-recombinant HBV vaccine booster at 10-14years of age. At endpoint (23-28years of age), we determined the HBV serological markers and quantified their serum HBV-DNA in each of the chronic HBV-infected adults.
Fifty-seven adults were identified as chronic HBV infection, indicated by HBsAg(+)&anti-HBc(+) for more than 6months. The individuals who were born to HBsAg-positive mothers (high-risk adults) had significantly increased risk of developing chronic HBV infections in adulthood compared with those who were born to HBsAg-negative mothers; the adjusted odds ratio (OR) was 12.56, 95%CI:7.14-22.08. The seronegative status of anti-HBs at 10-11years of age significantly increased the risk of HBV infections among the high-risk adults. When HBsAg(-)&anti-HBc(+) children who were born to HBsAg-positive mothers 70% of them remained as the status and 10% of them developed HBsAg(+)&anti-HBc(+). While when they were born to HBsAg-negative mothers 1.05% HBsAg(-)&anti-HBc(+) children developed HBsAg(+)&anti-HBc(+) and 24.74% of them remained as the status in 12-18years. One dose of adolescent booster showed significant protection on high-risk adults from chronic HBV infection; P for trend was 0.015.
Maternal HBsAg-positive status was an independent risk factor for vaccination-protected children to develop HBV breakthrough infection in adulthood. Adolescent boosters might be appropriate for high-risk individuals who were born to HBsAg-positive mothers when their serum anti-HBs<10mIU/ml.
接种乙型肝炎病毒（HBV）疫苗后产生的针对HBV表面抗原（HBsAg）的中和抗体（抗-HBs）在10 - 15年后会逐渐减弱。我们分析了对不同HBsAg携带状态母亲所生的、已通过疫苗接种获得保护的儿童进行青春期加强免疫，对其成年后预防HBV感染的效果。
纳入“启东乙肝干预研究”疫苗接种组中总共9793名个体，这些个体在儿童期（基线）时HBsAg阴性，且在儿童期和成年期均捐献了血样。其中7414人在10 - 14岁时接受了一剂10μg重组HBV疫苗加强免疫。在终点（23 - 28岁）时，我们检测了每例慢性HBV感染成年人的HBV血清学标志物，并对其血清HBV-DNA进行定量。
57名成年人被确定为慢性HBV感染，定义为HBsAg(+)&抗-HBc(+)持续超过6个月。与HBsAg阴性母亲所生的个体相比，HBsAg阳性母亲所生的个体（高危成年人）成年后发生慢性HBV感染的风险显著增加；调整后的优势比（OR）为12.56，95%置信区间：7.14 - 22.08。10 - 11岁时抗-HBs血清学阴性状态显著增加了高危成年人中HBV感染的风险。HBsAg阳性母亲所生的HBsAg(-)&抗-HBc(+)儿童中，70%维持该状态，10%发展为HBsAg(+)&抗-HBc(+)。而HBsAg阴性母亲所生的HBsAg(-)&抗-HBc(+)儿童中，1.05%发展为HBsAg(+)&抗-HBc(+)，24.74%在12 - 18岁时维持该状态。一剂青春期加强免疫对高危成年人预防慢性HBV感染显示出显著的保护作用；趋势P值为0.015。
母亲HBsAg阳性状态是疫苗接种保护儿童成年后发生HBV突破性感染的独立危险因素。对于HBsAg阳性母亲所生的高危个体，当血清抗-HBs<10mIU/ml时，青春期加强免疫可能是合适的。
