文章摘要
颜丙玉,吕静静,冯艺,曹传昭,孟鑫,梁晓峰,王富珍,徐爱强,张丽.乙型肝炎疫苗无应答成年人再次免疫后8年抗体持久性观察[J].中华流行病学杂志,2021,42(9):1546-1552
乙型肝炎疫苗无应答成年人再次免疫后8年抗体持久性观察
Antibodies persistence after revaccination with three doses of hepatitis B vaccine in non-responsive adults: results from 8-year follow-up study
收稿日期:2021-03-19  出版日期:2021-09-27
DOI:10.3760/cma.j.cn112338-20210319-00223
中文关键词: 乙型肝炎疫苗;无应答者;免疫;抗体持久性;成年人
英文关键词: Hepatitis B vaccine;Non-responder;Vaccination;Immune persistence;Adult
基金项目:国家科技重大专项(2018ZX10721202);山东省泰山学者工程(ts201511105)
作者单位E-mail
颜丙玉 山东省疾病预防控制中心免疫预防管理所/山东省传染病预防控制重点实验室, 济南 250014  
吕静静 山东省疾病预防控制中心免疫预防管理所/山东省传染病预防控制重点实验室, 济南 250014  
冯艺 山东省疾病预防控制中心免疫预防管理所/山东省传染病预防控制重点实验室, 济南 250014  
曹传昭 济南市章丘区疾病预防控制中心计划免疫科 250200  
孟鑫 山东省疾病预防控制中心免疫预防管理所/山东省传染病预防控制重点实验室, 济南 250014  
梁晓峰 暨南大学基础医学与公共卫生学院, 广州 510632  
王富珍 中国疾病预防控制中心免疫规划中心, 北京 100050  
徐爱强 山东省疾病预防控制中心免疫预防管理所/山东省传染病预防控制重点实验室, 济南 250014 aqxuepi@163.com 
张丽 山东省疾病预防控制中心免疫预防管理所/山东省传染病预防控制重点实验室, 济南 250014 zl9127@163.com 
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中文摘要:
      目的 评价成年人乙型肝炎(乙肝)疫苗(HepB)初次免疫(初免)无应答者再次免疫(再免)后8年的抗体持久性。方法 2009年8-9月选择济南市章丘区农村社区作为研究现场。研究对象纳入标准为18~49岁、本地常住人口、既往无HBV感染史和HepB接种史、健康状况良好者。按照"0-1-6"程序完成3剂次HepB初免的无应答成年人进行3剂次再免,分别于再免后1个月(T1)、2年、4年和8年采集静脉血,采用化学发光微粒子免疫分析法(CMIA)检测抗-HBs、HBsAg和抗-HBc。结果 再免后T1、2年、4年和8年时抗-HBs阳性率分别为85.12%(549/645)、60.60%(283/467)、55.90%(199/356)和55.09%(222/403),其中前2年、3~4年和5~8年的年均递减率分别为15.62%、3.96%和0.36%;抗-HBs几何平均浓度(GMC)分别为153.92、21.43、15.02和13.68 mIU/ml,其中,前2年、3~4年和5~8年的年均递减率分别为62.69%、16.28%和2.31%。多因素分析结果显示,再免后8年抗-HBs阳性率和GMC均与T1时抗-HBs水平独立相关,与T1时抗-HBs GMC<100 mIU/ml者相比,T1时GMC为100~和≥ 1 000 mIU/ml者再免后8年抗-HBs阳性率(OR值分别为14.13和62.91)和GMC(β值分别为1.88和3.24)均较高(均P<0.001)。再免后8年无HBsAg阳转者,抗-HBc阳转率为14.14%(57/403)。结论 成年人HepB初免无应答者3剂次再免后,抗体在前4年衰减较快,5年后进入稳定状态,再免后8年多数人抗-HBs仍维持在保护水平之上;抗体持久性主要与再免1个月时的抗体水平有关。
英文摘要:
      Objective To evaluate the persistence of HBsAg-specific antibodies eight years after revaccination with hepatitis B vaccine (HepB) among adults who were non-responsive to primary immunization. Methods From August to September 2009, rural communities in Zhangqiu district of Ji'nan city were selected as the study site. The subject's inclusion criteria were 18 to 49 years old, local resident population, without HBV infection history and HepB vaccination history, and good health status. Antibodies against hepatitis B surface antigen (anti-HBs) were detected in adults following the standard primary vaccination. Those who were non-responders (anti-HBs titer <10 mIU/ml) were revaccinated with three doses of HepB and included in the study. Blood samples were collected from all of them at one month (T1), two years, four years, and eight years after revaccination. The three indexes of anti-HBs, hepatitis B surface antigen (HBsAg), together with antibody against hepatitis B core antigen (anti-HBc), were measured by chemiluminescence microparticle immunoassay (CMIA). Results The proportion of subjects with anti-HBs titers ≥ 10 mIU/ml was 85.12% (549/645) at T1, 60.60% (283/467) at two years, 55.90% (199/356) at four years and 55.09% (222/403) at eight years after revaccination. The first two years' annual decline rates, three to four years and five to eight years, were 15.62%, 3.96%, and 0.36%. The GMC of anti-HBs was 153.92 mIU/ml at T1, 21.43 mIU/ml at two years, 15.02 mIU/ml at four years, and 13.68 mIU/ml at eight years. In the first two years, three to four years and five to eight years, the annual decline rate of GMC was 62.69%,16.28%, and 2.31%, respectively. Multivariable analysis showed that the titer of anti-HBs at T1 was independently associated with the persistence of anti-HBs at eight years after revaccination. Compared with anti-HBs titer <100 mIU/ml, those whose anti-HBs titers were 100-mIU/ml and ≥ 1 000 mIU/ml at T1 had a higher positive rate of anti-HBs (OR=14.13, P<0.001; OR=62.91, P<0.001) and a higher probability of anti-HBs titer (β=1.88, P<0.001; β=3.24, P<0.001) at 8 years after revaccination. Nobody was found seroconversion of HBsAg, and the anti-HBc positive rate was 14.14% (57/403). Conclusions Following revaccination with three doses of HepB in adults who were non-responsive to primary immunization, anti-HBs titers declined rapidly within the first four years. They then maintained a stable level after the fifth year. More than half still kept anti-HBs protective titer at eight years after revaccination. The immunity persistence was associated with anti-HBs titer at one month after revaccination.
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