乙型肝炎疫苗免疫持久性预防效果的定人研究

报告了新生儿乙型肝炎（乙肝）血源疫苗免疫后１－９年的抗－ＨＢｓ持久性。结果表明，母亲乙型肝炎病毒表面抗原（ＨＢｓＡｇ）阳性和阴性儿乙肝疫苗免疫后，抗－ＨＢｓ一率（Ｓ／Ｎ≥２．１）等１年分别为９３．７％和９８．６％，至８－９年已降低为６３．６％，而低抗体水平（≥２．１）仍在６０％以上。表明国产乙型肝炎血源疫苗免疫原性和持久性是好的。而对１９８５年的一批疫苗始终进行定量观察，至第１０年阳性率还能达到６     

新生儿乙型肝炎疫苗免疫后13年效果观察

目的 研究乙型肝炎的远期免疫效果。方法 采用单纯随机方法连续13年对1986年出生并接种乙型肝炎疫苗的儿童进行隔年随访,采血检测HBsAg、抗-HBs、抗-HBc。结果 13年间HBsAg阳性率在0.46%-0.97%之间,未随免疫时间的延长而上升,乙型肝炎疫苗的远期保护效果为81.67%,与近期免疫效果相当。结论 免疫后13年仍无需加强免疫。     

广东省佛山市新生儿乙型肝炎血源疫苗免疫后1—7？…

１９９４年抽查佛山市１９８７－１９９３年出生时经乙型肝炎（乙肝）疫苗免疫的儿童共９６１例，用国产放射免疫（ＲＩＡ）药盒检测，结果，免疫儿童的抗－ＨＢｓ一率由后１年的８４．０％降至免疫后７年的６９．２％；免疫后１－７年儿童的ＨＢｓＡｇ阳性率由免疫前的１６．９％下降至１．３５％；保护率达９２．０％；抗ＨＢｃ阳性率由免疫前的４０．９％下降至３．６％。表明新生儿经乙肝疫苗免疫后７年仍具有良好的免疫保护效果     

国产乙型肝炎血源疫苗免疫持久性观察

对１０６９名儿童乙型肝炎血源疫苗免疫后抗乙型肝炎病毒表面抗原的抗体水平进行检测，结果表明，抗－ＨＢｓ阳转率为９４．３％；初免后５年抗－ＨＢｓ阳转率仍可保持为９２．３％不同初免年龄免疫后抗－ＨＢｓ阳转率和持续时间未见明显差异。提示：为减少我国乙型肝炎发病率和乙型肝炎病毒携带者，用乙肝疫苗免疫接种是防止ＨＢＶ传播最有效的措施，经过正确接种疫苗后的９５％的接种者可具有免疫力；新生儿和婴幼儿接种乙型肝炎疫     

乙型肝炎疫苗长期免疫效果评价及免疫持久性研究

目的 评价我国新生儿乙型肝炎(乙肝)疫苗免疫后的长期保护效果,为乙肝防控和乙肝疫苗HepB免疫策略提供参考.方法 用横断面调查和分层整群抽样的方法,在乙肝疫苗免疫效果观察监测点收集1987-1996年出生(13～22岁)、全程接种乙肝血源疫苗的人群,以及1997-2008年出生(1 ～ 12岁)、全程接种乙肝重组酵母疫苗人群的血清样本和资料;用微粒子酶免疫法检测HBV感染指标,结合本底资料和乙肝疫苗免疫史进行分析.结果 在河北正定、广西隆安、上海黄浦、青海同德和湖南湘潭5个监测点共收集1～12岁重组酵母疫苗免疫人群样本8133例,13 ～22岁血源疫苗免疫人群样本4848例,5个监测点的HBsAg平均阳性率均显著低于本底值,疫苗总体保护效果分别为86.04％～96.14％;河北正定、青海同德和湖南湘潭的年龄分布差异无统计学意义,广西隆安和上海黄浦的结果显示19～22岁人群HBsAg阳性率偏高;Anti-HBs阳性率随免疫年龄增长而下降,重组疫苗免疫人群从1～2岁组的86.84％下降至11～12岁组的46.40％,17 ～18岁组的Anti-HBs阳性率处于较低水平,而19～22岁组出现升高;几何平均浓度(GMC) ＜10 mIU/ml(Anti-HBs阴性)的比例随着年龄增长逐渐升高,100～999.99 mIU/ml和≥1000 mIU/ml的比例随着年龄的增长呈现下降趋势.结论 血源疫苗免疫后13～ 22年、重组酵母疫苗免疫后1～12年的总体保护效果良好;不必开展加强免疫,建议加强监测18岁以上人群的Anti-HBs水平,对GMC＜10 mIU/ml者开展加强免疫.     

Pre-S_2抗原在乙肝疫苗中的免疫作用的探讨

比较三种乙型肝炎血源疫苗和一种重组DNA(r-DNA)疫苗诱导Pre-S_2抗体阳性率与阻断乙型肝炎病毒母婴传播的有效率,其中rDNA疫苗不含有Pre-S_2蛋白,免疫后不产生Pre-S_2抗体,加热灭活疫苗按3μg与6μg两种剂量免疫后,半数以上对象均可产生Pre-S_2抗体,甲醛一步法灭活疫苗免疫后有30％婴儿产生Pre-S_2抗体。阻断母婴传播的有效率分别为:rDNA疫苗72.2％,甲醛一步法灭活疫苗70.1％,加热灭活疫苗3μg组35.6％,6μg组71.9％。疫苗免疫效果同HBsAg含量有关,似同Pre-S_2蛋白关系不明显。免疫后抗HBs阳性率与反映抗HBs含量的S/N值均同Pre-S_2抗体阳性率没有明显联系。Pre-S_2蛋白似非决定乙肝疫苗有效率的主要成分,而疫苗中的S蛋白含量对疫苗的免疫效果起十分重要作用。     

新生儿乙型肝炎疫苗免疫后首次检测为乙型肝炎病…

报告了新生儿乙型肝炎（乙肝）疫苗免疫后１－９年的ＨＢｓＡｇ阳性者年阴转率的定人随访结果。母亲ＨＢｓＡｇ阳性儿，乙肝疫苗免疫后首次检出的８４例ＨＢｓＡｇ阳性者，动态观察了１－９年，ＨＢｓＡｇ年抗ＨＢｓ，２／１０无抗－ＨＢｓ应答。结论：母婴阻断失败者的ＨＢｓＡｇ阳性儿，其ＨＢｓＡｇ年阴转率很低，和人群观察结果（１．１１％）相似；阴转者８０％能够产生抗－ＨＢｓＡｇ阳性儿，其ＨＢｓＡｇ年阴转率很低，和人群     

不同剂量乙型肝炎疫苗阻断母婴传播的长期效果观察

在１９８６年与１９８８年分别对湘潭市１４７名乙型肝炎病毒表面抗原（ＨＢｓＡｇ）和ｃ抗原（ＨＢｃＡｇ）双一母亲所生的新生儿，采用不同剂量的乙型肝炎（乙肝）疫苗阻断母婴传播，并进行长期观察。免疫后１年新生儿抗－ＨＢｓ阳性率８８组为８０．００％（７６／９５），８６组为６７．３１％（３５／５２），两组相比较无显著性差异；免疫后９年，两组的抗－ＨＢｓ一率仍无差异。免疫后１年新生儿的ＨＢｓＡｇ阳性率８６组为０     

B7-2表达质粒对HBV DNA疫苗诱导的特异性免疫应答的影响

目的：探讨B7－2分子是否能够增强乙型肝炎病毒（HBV）DNA疫苗诱导的特异性免疫应答。方法：将B7－2表达质粒与HBV DNA疫苗共接种于小鼠腓肠肌内，检测细胞毒性T淋巴细胞（CTL）活性，迟发性超敏反应（DTH）及抗－HBs滴度。结果：B7－2表达质粒与HBV DNA疫苗共接种组的DTH反应和CTL活性，明显强于单独接种HBV DNA疫苗组（P＜0．01）。两组的抗－HBs滴度差异无显著性（P＞0．05）。结论：B7－2表达质粒与HBV DNA疫苗共接种可显著增强抗－HBV特异性细胞免疫应答（CMI）。     

新生儿乙型肝炎疫苗免疫后远期效果的研究

对湘潭市市区０－１０岁儿童乙型肝炎（乙肝）疫苗免疫后的效果进行了系统监测。６次共调查儿时１２２名，各次调查的乙型肝炎病毒表面抗原（ＨＢｓＡｇ）携带率在０．００１－１．８３％之间，平均ＨＢｓＡｇ携带率１．１２％，明显低于免疫前现一人群的１６．１７％，保护率为９２．４６％。初次免疫后抗－ＨＢｓ的阳经及几何平均滴度（ＧＭＴ）高峰值均出现在６－１２个月，此后随时间的推移而逐渐下降，但７－１０岁儿童中仍有５     

Antibody persistence and immune memory in adults, 15 years after a three-dose schedule of a combined hepatitis A and B vaccine

A combined hepatitis A and B vaccine is available since 1996. Two separate open‐label primary studies evaluated the immunogenicity and safety of this hepatitis A and B vaccine (720 EI.U of HAV and 20 µg of HBsAg) in 306 healthy subjects aged 17–43 years who received three doses of the vaccine following a 0, 1, and 6 months schedule. These subjects were followed up annually for the next 15 years to evaluate long‐term persistence of anti‐HAV and anti‐HBs antibodies. The subjects whose antibody concentrations fell below the cut‐offs between Year 11 and Year 15 (anti‐HAV: <15 mIU/ml; anti‐HBs: <10 mIU/ml) were offered an additional dose of the appropriate monovalent hepatitis A and/or B vaccine. In subjects who received the additional vaccine dose, a blood sample was collected 1 month after vaccination. At the Year 15 time point, all subjects in Study A and Study B were seropositive for anti‐HAV antibodies and 89.3% and 92.9% of subjects in the respective studies had anti‐HBs antibody concentrations ≥10 mIU/ml. Four subjects (two in each study) received an additional dose of monovalent hepatitis B vaccine and mounted anamnestic responses to vaccination. No vaccine‐related serious adverse events were reported. This study confirms the long‐term immunogenicity of the three‐dose regimen of the combined hepatitis A and B vaccine, as eliciting long‐term persistence of antibodies and immune memory against hepatitis A and B for up to at least 15 years after a primary vaccination. J. Med. Virol. 84:11–17, 2011. © 2011 Wiley Periodicals, Inc.     

Prevalence of serologic markers of the hepatitis B virus in pregnant women of Bamako, Mali

A prospective study of the serological markers of hepatitis B virus (HBV) including hepatitis B virus surface antigen (HBsAg) and hepatitis B surface antibody (anti HBs) was conducted over 5 years in Bamako. The aims of this study were to assess the prevalence of HBsAg in pregnant women and to determine the risk of HBV infection for this population. The study involved 829 pregnant women for whom blood samples were collected after the first quarter of pregnancy. HBsAg and anti HBs were detected in all cases by radioimmunoassay. The prevalence of HBsAg and anti HBs in pregnant women was respectively 15.5% and 16.9%. This prevalence of HBsAg, higher than in the general population, points to the fact that pregnant women are a high risk group for hepatitis B infection. In addition, scarification and tattooing practices increase significantly the risk of infection by hepatitis B virus (OR = 2.03; 1.07 < OR < 3.82; chi 2 = 5.62; p: 1%). Thus, we can presumably conclude that infants and new borns in such conditions are largely exposed to hepatitis B virus infection, even though hepatitis B core antibody and hepatitis B e antigen were not investigated for technical reasons. In conclusion, the authors believe that infants and new borns must be systematically immunised against hepatitis B virus infection in Bamako.     

The prevalence of antibodies to human herpesvirus 8 and hepatitis B virus in patients in two hospitals in Tanzania

The aim of this study was to determine the seroprevalence of human herpesvirus 8 (HHV‐8) and the immunization status for hepatitis B virus (HBV) infection in febrile patients in two districts of the United Republic of Tanzania. Between February and March 2007, blood samples were collected in Pemba Island and Tosamaganga from 336 outpatients and sent to the Virology Laboratory in Rome (Italy) for testing. HHV‐8 DNA and HBV‐DNA were amplified by two in‐house molecular methods, anti‐HHV‐8 antibody titers were determined by an immunofluorescence assay (IFA), and anti‐HCV, HBsAg, anti‐HBs, and anti‐HBc were evaluated by microplate enzyme immunoassay (MEIA). The seroprevalence of HHV‐8 was 30.7% (96/313). In Pemba Island, the prevalence was lower than in Tosamaganga (14.4% vs. 46.3%). A higher prevalence of low titers of HHV‐8 IgG (<1:80, 81%) was found among those under 5 years of age. HHV‐8 DNA was detected in six seropositive patients (6.7%). The prevalence of HBsAg, anti‐HBs, and anti‐HBc was 4.3%, 37.6%, and 29.3%, respectively. Out of 277 patients, 70 had had a previous infection (25.3%). One case of occult hepatitis was found. The cover of hepatitis B vaccination was higher among children born after 2002 (66.7%) than in patients born before 2002. HHV‐8 infection is endemic in Tanzania and the seroprevalence rate was higher in the mainland than on Pemba Island. The 3.9% percentage of HBsAg in children younger than 4 years of age suggests that increased efforts are required in order to achieve universal and compulsory immunization of children against HBV. J. Med. Virol. 82:1569–1575, 2010. © 2010 Wiley‐Liss, Inc.     

广州某高等医学院校研究生乙肝疫苗接种情况调查

目的了解广州某高等医学院校研究生乙肝疫苗接种情况，为乙肝防治工作提供依据。方法对广州某高等医学院校2006年入学的1139名研究生进行入学体检现况调查，采集血标本用ELISA法检测乙型肝炎表面抗原（HBsAg）和表面抗体（HBsAb）。同时发放乙肝疫苗接种情况调查表，调查乙肝疫苗接种的年代、次数，是否加强接种及时间。用SAS统计软件包对结果进行X^2检验分析。结果广州某高等医学院校06级研究生HBsAg阳性率为2．90％，曾注射乙肝疫苗组，HBsAg阳性率显著低于从未注射疫苗组（1．15％ vs． 21．69％，P〈0．0001），而HBsAb阳性率则显著高于从未注射疫苗组（81．54％ vs．44．58％，P〈0．0001）。有17．31％曾接种乙肝疫苗者未能达到预期预防效果。不同年龄研究生乙肝疫苗接种效果有差异（P=0．0462），随着年龄的增加，HBsAb阳性率有下降趋势。女性乙肝疫苗接种效果较男性好（80．0％ vs．84．87％，P=0．0468）。接种年限在3年内者，HBsAb阳性率较其他年限高（0—3年 vs．4—6年，P=0．0089；0—3年 vs．7—9年，P=0．0172；0—3年 vs．〉9年，P=0，0474）。注射大于3针（即加强接种）免疫效果较注射3针者好，差异有统计学意义（P=0．0093）。结论随着年龄的增加，乙肝疫苗接种效果（HBsAb阳性率）逐渐降低。男性群体较女性群体更易成为乙型肝炎病毒的易感人群。对接种年限大于3年者，可进行抗-HBs监测，及时进行加强免疫。     

Association of concurrent hepatitis B surface antigen and antibody to hepatitis B surface antigen with hepatocellular carcinoma in chronic hepatitis B virus infection

Antibody to hepatitis B surface antigen (HBsAg) (anti‐HBs) can exist in patients with chronic hepatitis B virus (HBV) infection. To date, little is known about the association of concurrent HBsAg and anti‐HBs (concurrent HBsAg/ anti‐HBs) with hepatocellular carcinoma (HCC). The aim of this study was to investigate the clinical relevance of concurrent HBsAg/anti‐HBs with preS deletion mutations and HCC in chronic HBV infection. A total of 755 patients with chronic HBV infection were included consecutively at a tertiary center. Logistic regression analysis was used to identify risk factors for HCC, and serum HBV DNA was amplified, followed by direct sequencing to detect preS deletions. The prevalence of concurrent HBsAg/anti‐HBs was 6.4% (48/755) and all HBVs tested were genotype C. HCC occurred more frequently in the concurrent HBsAg/anti‐HBs group than in the HBsAg only group [22.9% (11/48) vs. 7.9% (56/707), P = 0.002]. In multivariate analyses, age >40 years [odds ratio (OR), 14.712; 95% confidence interval (CI), 4.365–49.579; P < 0.001], male gender (OR 2.431; 95% CI, 1.226–4.820; P = 0.011), decompensated cirrhosis (OR, 3.642; 95% CI, 1.788–7.421; P < 0.001) and concurrent HBsAg/anti‐HBs (OR, 4.336; 95% CI, 1.956–9.613; P < 0.001) were associated independently with HCC. In molecular analysis, preS deletion mutations were more frequent in the concurrent HBsAg/anti‐HBs and HCC groups than in the HBsAg without HCC group (42.3% and 32.5% vs. 11.3%; P = 0.002 and 0.012, respectively). In conclusion, concurrent HBsAg/anti‐HBs is associated with preS deletion mutations and may be one of the risk factors for HCC in chronic HBV infection with genotype C. J. Med. Virol. 81:1531–1538, 2009. © 2009 Wiley‐Liss, Inc.     

HBsAg阳性儿童和健康儿童对国产甲型肝炎灭活疫苗免疫原性和安全性的观察

目的：观察HBsAg阳性儿童对国产甲型肝炎灭活疫苗的免疫原性和安全性。方法：随机选取121名1－10岁健康儿童和10名同龄的HBsAg阳性儿童，抗－HAV均阴性，接种唐山怡安生物工程有限公司研制的甲型肝炎灭活疫苗。接种剂量为500U／剂和1000U／剂两组，免疫程序为0和6个月，并在初免后30d，第二针后30和180d用ELISA方法检测抗－HAV。结果：HBsAg阳性儿童和健康儿童接种500U／剂和1000U／剂甲型肝炎灭活疫苗后抗体阳转率均为100％。第二针免疫后30d抗体平均几何滴度500U／剂组分别为4684．9mIU和4535．6mIU；1000U／剂组分别为5399．8mIU和7347．1mIU。二者比较差异无显著性，免疫后亦未见异常反应，初免后1年抗体水平仍然很高。结论：HBsAg阳性儿童接种国产甲型肝炎灭活疫苗具有良好的免疫应答，同时也是安全的。     

Hepatitis B vaccination in children: The Taiwan experience

The world's first nationwide hepatitis B virus (HBV) universal vaccination program for infants was launched in Taiwan in July, 1984. All infants received three to four doses plasma or recombinant HBV vaccines. In addition, infants of HBeAg-positive mothers received 0.5 ml of hepatitis B immunoglobulin within 24 hours after birth. The vaccination coverage rate is as high as 97%. Seroprevalence of hepatitis B surface antigen (HBsAg) declined from 9.8% (prevaccination period) to 0.6% in children in Taipei City after 20 years of mass vaccination. The seropositive rates for HBsAg, antibody to HBsAg, and antibody to hepatitis B core antigen were 1.2%, 50.5%, and 3.7%, respectively, in those born after the vaccination program (< 20 years old) in 2004. In line with the decrease of chronic HBV infection, the incidence of hepatocellular carcinoma (HCC) also decreased in children in Taiwan. From 1981 to 1994, the incidence of HCC in 6- to 9-year-olds declined from 0.52/100,000 for those born between 1974 and 1984 to 0.13 for those born between 1984 and 1986 (p < 0.001). We extended the observation to 2000, the incidence of HCC per 100,000 children declined from 0.54 to 0.20. The prevalence of a determinant mutants (amino acids 121–149 of HBsAg) in Taiwanese carrier children was 7.8% (eight out of 103) in 1984, increased to 19.6% (10 out of 51) in 1989, peaked at 28.1% (nince out of 32) in 1994, and remained stationary at 23.1% (three out of 13) and about 25% in 1999 and 2004, respectively; it was higher in those fully vaccinated compared with those not vaccinated. The other group of subjects who are susceptible to vaccine failure is the immunocompromized hosts. We observed some de novo HBV infection in children after liver transplantation. Despite of the success of hepatitis B immunization, childhood chronic HBV infection and HCC were not eliminated by the universal vaccination program. Among those HBsAg carriers born after the vaccination program, 89% of their mothers were found to be positive for HBsAg, indicating the importance of maternal transmission. This was also true in the mothers of children with HCC, of them 96% were HBsAg positive. After two decades of universal infant HBV vaccination, we found this program provides long-term protection for up to more than 20 years, and a universal booster is not required for the primary HBV vaccinees before adulthood. Mother-to-child transmission, although largely diminished, is still the main cause for immunoprophylaxis failure. The emergence of escape mutant did not impose increased risk of chronic infection at present. Nevertheless, development of new vaccines may overcome the vaccine failure.     

Reactivation of occult hepatitis B virus infection following cytotoxic lymphoma therapy in an anti‐HBc negative patient

Screening hepatitis B virus (HBV) surface antigen (HBsAg) and HBV core antibody (anti‐HBc) is recommended prior to cytotoxic or immunosuppressive therapy. This case describes an anti‐HBc negative, DNA positive occult HBV infection in a 71‐year‐old Caucasian male following rituximab‐based treatment for follicular lymphoma. Pre‐screening serology indicated negative HBsAg and anti‐HBc. However, following sequential treatment cycles the patient developed weak HBsAg with a low HBV DNA load (<1,000 IU/ml), but remained anti‐HBc negative. The DNA load peaked 5 months later (>1 × 10⁶ IU/ml) and he was subsequently treated with Tenofovir. Currently the patient remains anti‐HBc negative, and is anti‐HBe negative, anti‐HBs negative, HBeAg positive. No clinical or biochemical evidence of hepatitis has occurred. Sequencing and phylogenetic analysis identified the HBV genosubtype as D4, most probably acquired some years ago during a stay in Papua New Guinea, in spite of prior hepatitis B vaccination. Four amino acid substitutions were detected within the HBsAg loop yet none in the core protein. This case questions the dependability of anti‐HBc testing and highlights the role of HBV DNA testing prior to and throughout cytotoxic or immunosuppressive regimes. As this case exemplifies, vaccination protects against clinical infection but may not exclude seronegative occult infection with the possibility of reactivation. J. Med. Virol. 85:597–601, 2013. © 2013 Wiley Periodicals, Inc.     

Humoral and Cellular Responses to a Single Dose of Fendrix in Renal Transplant Recipients with Non‐response to Previous Hepatitis B Vaccination

Approximately 70% of kidney transplant recipients are non‐responders to conventional hepatitis B virus (HBV) vaccines. We examined whether Fendrix™, an HBV vaccine containing 3‐O‐desacyl‐4′‐monophosphoryl lipid A (MPL) as adjuvant, could induce HBV immunity in these patients and compared their vaccination efficacy with healthy controls tested previously by the same assays. We selected 35 kidney transplant recipients who had been vaccinated at least thrice against HBV but had never displayed anti‐HBs antibodies. We re‐assessed their anti‐HBs antibody titres and further determined cellular HBV immunity by proliferation assay and interferon (IFN)‐γ ELISpot. Seventeen recipients did neither display humoral nor cellular immunity and could be tested prior to and at month 1 after vaccination. Of note, HLA antigens associated with non‐response to HBV vaccination (HLA‐DRB1*03 and HLA‐DQB1*02) were over‐represented in these 17 recipients. At month 1 after a single vaccination with Fendrix™, we observed a significant increase in anti‐HBs antibodies (P = 0.02). In seven of 17 recipients, we detected anti‐HBs antibodies ≥10 IU/l (10–264), in four HBV‐specific lymphocyte proliferation (stimulation index of 2.6–8.7) and in one specific IFN‐γ responses (12 spots increment). The vaccination response to Fendrix™ was significantly higher (P = 0.035) than the response to HBVaxPro™ in young healthy controls. In summary, the results show that a single vaccination with Fendrix^™ could already induce HBV‐specific humoral and/or cellular responses in ten of 17 kidney transplant patients. Thus, Fendrix™ appears as an efficient vaccine in this patient cohort.