国产与进口重组酵母乙肝疫苗阻断母婴传播乙肝的研究

为评价不同重组酵母乙肝疫苗阻断乙型肝炎病毒（ＨＢＶ）母婴传播的效果，将ＨＢｓＡｇ，ＡＢｅＡｇ双阳性母亲所生的１０５名婴儿分为５组，分别采用美国Ａｍｇｅｎ（１０μｇ／支），北京（５μｇ／支），美国Ｍｅｒｃｋ（５μｇ／支），日本熊本（１０μｇ／支）及康泰...     

中效价乙型肝炎免疫球蛋白与乙型肝炎疫苗合用阻断母婴传播的效果

用ＲＰＨＡ及ＥＩＡ法筛ＨＢｓＡｇ、ＨＢｅＡｇ双阳性孕妇，其新生儿分两组，以６０ＩＵ／ｍｌ１针免疫球蛋白（ＨＢＩｇ）加３针１０μｇ乙型肝炎疫苗为实验组，于出生２４小时内分别在左右上臂三角肌内接种１支ＨＢＩｇ和１支乙肝疫苗，１、６个月时各接种１支１０μｇ乙肝疫苗，用同剂量、同批号、同方法接种乙型肝炎疫苗３针为对照组。均于出生后１、６、９个月采静脉血进行血清学检测。结果显示，免后６、９个月对照组和实验组的ＨＢｓＡｇ阳转率分别为７．５％、５．３％。保护率为９０．４％和９３．２％，达到３０μｇ疫苗加２００ＩＵ／ｍｌＨＢＩｇ免疫局６个月的保护率（７６．５％～９２．２％）。两组ＨＢｓＡｇ阳转率、保护率、Ｓ／Ｎ值ＧＭＴ的差异非常显著，ｘ２＝７．５２，Ｐ＜０．０１。表明中效价ＨＢＩｇ与乙肝疫苗共同应用，对主动免疫应答无抑制现象。     

儿童接种两针乙型肝炎疫苗1—10年免疫效果的队列…

农村１－７岁易感儿童，按０、３程式接种两针１０μｇ乙型肝炎（乙肝）疫苗，进行了１０年免疫效果的队列研究。结果表明，乙型肝炎病毒表面抗体（抗－ＨＢｓ）阳经随免疫年限延长逐渐下降，免疫后１０年阳性率仍有５９．８％；免疫组儿童观察期间ＨＢｓＡｇ年阳转率由免疫前的１．３％下降到０．０５％，保护率为９６．２％；在免疫屏障的保护作用下，对照组ＨＢｓＡｇ年阳转率为０．４１％，也比免疫前降低了６８．５％；疫苗组与     

重组酵母乙肝疫苗免疫效果研究

目的研究重组酵母乙肝疫苗对青少年学生的免疫效果。方法同时对３６５名乙肝病毒血清学指标（ＨＢＶ－Ｍ）不同感染状况的学生进行免疫监测。随机分为两组，Ａ组：１８３人，接种剂量１０－５－５（μｇ），Ｂ组：１８２人，接种剂量５－５－５（μｇ），用ＥＬＩＳＡ法，在全自动酶标分析仪上测定。结果１．重组酵母乙肝疫苗对青少年免疫效果良好，抗－ＨＢｓ阳性率达９７％以上；２．对ＨＢＶ－Ｍ不同感染状况的学生，免疫后均无不良反应。结论ＨＢＶ易感者和感染者接种疫苗后免疫效果均好。在青少年中普种乙肝疫苗可不筛查ＨＢＶ－Ｍ。     

单克隆抗体B159－表阿霉素结合物的研制及活性鉴定

本文报道蒽环类抗癌新药表阿霉素通过支联剂葡聚糖Ｔ１０与Ｂ淋巴细胞白血病单克隆抗体Ｂ１５９交联组成的Ｂ１５９－Ｄｅｘ－ＥＰＩ结合物，每克分子抗体可携带１４克分子的药物。在制备过程中结合物中抗体活性无损失。结合物对靶细胞具有较强的选择性细胞毒作用（ＩＣ５０为０．８８μｇ／ｍｌ），明显优于游离表阿霉素（ＩＣ５０为２．７μｇ／ｍｌ）及无关抗体结合物（ＩＣ５０＞３０μｇ／ｍｌ），对非靶细胞毒性较弱（ＩＣ５０＞３０μｇ／ｍｌ）。     

一种新生和乙型肝炎疫苗免疫方案的长期效果考核

对上海市南市区１９８６年出生并接种乙型肝炎（乙肝）疫苗的儿童进行了９年的血清学随访。这些儿童乙肝疫苗的免疫量为母亲乙肝炎病毒表面抗原（ＨＢｓＡｇ）阳性者给予三剂２０μｇ，阴性者给予三剂１０μｇ，其中母亲ＨＢｓＡｇ阳性者约占６．１６％。免疫后１－９年内各次随访的血清ＨＢｓＡｇ阳性率在１％以下波动，没有随年龄增长而升高；在免疫后第９年共检测４６８例血清，无１例ＨＢｓＡｇ阳性，大大低于免疫前本底对照５－     

广东省佛山市新生儿接种30—10—10μg乙型肝炎疫…

１９９１－１９９５年，对佛山市１９８８－１９８９年出生时接种３０－１０－１０μｇ乙型肝炎（乙肝）疫苗的儿童进行免疫效果长期观察。采用放射免疫（ＲＩＡ）法及国产试剂检测，共有２２９例被定期随访，１６９３人次被抽样受检。结果，至免疫后７年，抗－ＨＢｓ阳性（≥１０ｍＩ／ｍｌ）率由第３年的８０．８％下降至６０．３％；ＨＢｓＡｇ的阳性（Ｓ／Ｎ≥１０．０）率由第３．３８％下降至２．５３％，此时预防ＨＢｓＡｇ阳     

用基因重组乙肝表面抗原与血源乙肝表面抗原检测抗-HBs的比较

目前 ,基因重组酵母乙肝疫苗已被广泛应用 ,在对该疫苗免疫效果观察中发现 ,用原有的检测抗 ＨＢｓ的ＲＩＡ试剂检测基因重组疫苗 ,免后所得的抗体阳转率及抗体几何平均滴度 (ＧＭＴ)低于血源疫苗免后效果 ,但是母婴阻断效果却显示基因重组疫苗优于血源疫苗〔1〕。针对基因重组疫苗免疫效果中的结果不一致 ,有学者对不同来源的乙肝表面抗原进行了分析 ,发现基因重组抗原和血源抗原在表位密度上有一定的差别〔2 ,3〕。评价疫苗的免疫效果 ,很重要的方法是测定接种者的抗体水平。由此提出用相应抗原制备试剂检测相应抗体 ,将会对基因重组乙肝…     

乙型肝炎基因工程疫苗阻断乙型肝炎病毒母婴传播的研究

用转基因细胞（ＣＨＯ－Ｃ２８）分泌的乙型肝炎病毒表面抗原基因工程疫苗免疫母亲ＨＢｓＡｇ阳性的新生儿５０例，观察其阻断乙型肝炎病毒母婴传播的效果，随访１２个月，在３６例母亲为ＨＢｓＡｇ和ＨＢｅＡｇ均阳性的婴儿中仅１例为ＨＢｓＡｇ阳性，其余婴儿均有保护性抗体，预防保护率为９６．２％。１４例母亲单独ＨＢｓＡｇ阳性的所有婴儿抗ＨＢｓ均阳转，保护率达１００％。抗ＨＢｓ阳性的婴儿均具有较高抗体水平，抗ＨＢｓＧＭＴ为１１．１５６×１０５～１３．１３４×１０５ｍＩＵ／Ｌ。说明ＣＨＯ乙型肝炎基因工程疫苗具有较好的免疫原性和近期保护效果。     

新生儿乙肝酵母疫苗免疫后抗体无应答者的再免、加强免疫与细胞免疫的研究

目的HBsAg阴性母亲婴儿应用国产乙型肝炎重组酵母疫苗常规接种后的抗-HBs无应答者的再免、加强免疫效果,以及抗体阴性婴儿细胞免疫应答状况。方法在河南省开封市筛选8093例7~24月龄,母亲HBsAg阴性,按0、1、6月程序接种国产5μg乙肝酵母疫苗的健康婴儿,RIA法检测抗-HBs。对无应答者进行5μg×2或×3;10μg×2或×3剂4组疫苗再免、加强免疫效果的比较。随机选择加免后抗体阳性和仍阴性的婴儿,用ELISPOT方法测定PBMC体外刺激产生的IFN-r和IL-2。结果2970例7~10月龄婴儿中56例抗-HBs低于10mIU/ml者分4组再免后,抗-HBs阳转率>85%。而11~24月龄5933例中346例无应答者也同上分为4组。加强免疫后,抗-HBs阳转率为92.59%~97.92%,无统计学差异。10例加强免疫后抗体仍持续阴性婴儿TH1类细胞因子IL-2和IFN-r的阳性率分别为30%和20%,低于有应答人群(19/32,59.38%;11/32,37.04%)。结论母亲HBsAg阴性的婴儿常规接种5μg乙肝疫苗后抗体无应答者,用5μg、10μg两剂或三剂加强免疫都有良好的抗体阳转效果。加免抗体仍阴性婴儿与正常应答者存在明显的细胞免疫应答的差别。     

Targeting the mucosa: genetically engineered vaccines and mucosal immune responses

The discovery that inoculation of DNA leads to strong and long lasting immune responses generated enthusiasm to assess the efficacy of various genetically engineered vaccines against mucosally acquired infections. Various techniques have been used to generate the most suitable DNA vaccines, ranging from immunization with naked DNA to utilizing genetically engineered recombinant viruses and bacteria to deliver the DNA. Different DNA vaccine modalities and mucosal immune responses to them have been discussed. It has been shown that even though intramuscular and intradermal immunization with these vaccines generates strong systemic responses, mucosal responses are not induced. It has been proposed that the site of immunization determines mucosal immune responses and that primed lymphocytes preferentially accumulate at sites where they have been induced thus generating the strongest cellular and antibody responses at the site of vaccination. The impact of the site of induction on mucosal immune responses to vaccines is discussed. It is possible to enhance desired vaccine effects in the mucosa and to modify the undesirable side effects. Cytokines such as IL-2, IL-12, IL-15 and IL-18 have been used to enhance CTL activity while IL-5, IL-6 and the chemokine MIP-1 alpha have shown the capacity to increase IgA responses to vaccines.     

Simultaneous administration of diphtheria-tetanus-pertussis-polio and hepatitis B vaccines in a simplified immunization program: immune response to diphtheria toxoid, tetanus toxoid, pertussis, and hepatitis B surface antigen.

We studied the interactions of hepatitis B vaccine with other vaccines used in the World Health Organization expanded programs of immunization. Three groups of Senegalese children were vaccinated with hepatitis B vaccine (HB) alone, diphtheria-tetanus-pertussis (DTP)-polio vaccine alone, or a combination of hepatitis B vaccine and DTP-polio vaccines simultaneously. The immune responses to HBsAg, tetanus toxoid, diphtheria toxoid, and pertussis were measured after one and two vaccinations at 6-month intervals. The immune responses to the combination of HB vaccine and DTP-polio vaccines were similar to the immune responses observed after administration of each vaccine alone. In addition, no adverse reactions were noted. These experimental trials also demonstrated that with a DTP-polio vaccine containing 30Lf of tetanus and diphtheria toxoids, two doses given at 6-month intervals are sufficient to provide a satisfactory immune response. In the case of pertussis and HB vaccines; however, a third dose is necessary.     

人禽流感病毒H5N1多价重组痘苗病毒(天坛株)疫苗在小鼠中的免疫原性研究

目的 研发高效广谱的人高致病性禽流感病毒H5N1实验疫苗.方法 首先构建了含H5N1(安徽株)结构基因[血凝素(HA)、神经氨酸酶(NA)、基质蛋白M1与M2]的两个双顺反子(HAop/M2,NAop/M1)重组痘苗病毒(rTTV天坛株)疫苗,采用不同剂量(104 PFU或107PFU)或组合(疫苗单独或联合)方式于0、4周二次免疫BALB/c小鼠,初步比较分析抗原特异的体液(HA血凝抑制抗体、NA特异性抗体、中和抗体)与细胞免疫应答(IFN-γ ELISPOT)特点.结果 重组痘苗病毒疫苗可有效表达H5N1靶抗原;高剂量组的重组痘苗病毒疫苗可快速激发较强的针对各个抗原的抗体与针对血凝素与神经氨酸酶蛋白的细胞免疫应答,含血凝素蛋白的重组痘苗病毒疫苗亦可诱导明显的中和抗体;但各组重组痘苗病毒疫苗所激发的针对基质蛋白(M1,M2)的细胞免疫应答均较弱;两个双顺反子(HAop/M2,NAop/M1)重组痘苗病毒疫苗联合应用所激发的针对基质蛋白2(M2)的体液免疫应答明显强于单双顺反子(HAop/M2)疫苗单独应用.结论 本研究中制备的各组重组痘苗病毒疫苗可诱导多个抗原特异的体液与细胞免疫应答,该研究为新型H5N1疫苗的研发及免疫方案的优化奠定了基础.     

Antibody determination in an ongoing hepatitis B vaccination program

In an interim analysis of our ongoing immunization program against hepatitis B (HB), started in early 1982, we tested 283 serum samples from 77 female and 110 male vaccinees for antibody to HB surface antigen (anti-HBs). We compared two methods, Anti-HBs EIA (ROCHE) (method 1), which is a neutralization test, and AUSABR EIA (method 2), which is a double-antigen-sandwich test. The nonresponder rate (after the 12-month booster dose of Hevac B Pasteur) was 4% in females with both methods, in males 15% measured with method 1 and 11% measured with method 2. Five healthy HBsAg carriers were detected only by method 1. When the samples were grouped according to their anti-HBs titers, method 1 measured higher in samples taken after three vaccine doses and method 2 did so in samples collected after the 12-month booster dose. This tendency was confirmed with samples from slow responders who received a 4th vaccine dose soon after the initial three doses. We therefore confirm the efficacy of the plasma-derived HBsAg vaccine and validate the assay systems used to measure anti-HBs, one parameter of immunity to HB virus infection.     

乙型肝炎卡介苗联合疫苗与单价乙型肝炎疫苗免疫效果的比较

目的：比较乙型肝炎卡介苗联合疫苗与单价乙型肝炎疫苗的免疫效果。方法：实验动物采用豚鼠，按0、1、2月三针免疫程序接种，并于每针免疫后1个月采血，ELISA方法检测血清抗体滴度。实验分三部分进行。实验一：三种不同规格的联合疫苗与单价乙型肝炎疫苗的比较；实验二：同一规格连续三批联合疫苗与单价乙型肝炎疫苗的比较；实验三：联合疫苗与两种单价疫苗同时免疫的比较。结果：在三个实验中，联合疫苗组第一针血清抗体滴度均低于对照组，但无统计学差异：联合疫苗组第二、三针血清抗体滴度均高于对照组，也无统计学差异，实验组各组之间无明显差异。结论：联合疫苗组三针免疫程序的HBsAg的效力与单价乙型肝炎疫苗组相似。     

Hepatitis B vaccination status in an at-risk adult population: long-term immunity but insufficient coverage

In France, hepatitis B (HB) vaccine has been offered to all infants since 1994, and was proposed to all children aged 11 years from 1994 to 1998. Nevertheless, HB vaccine hesitancy may result in low vaccination coverage in present-day at-risk adults. We aimed to determine HB vaccination coverage in adults attending a free testing center for sexually transmitted infections (STI). As part of routine care, three classes of data were anonymously collected from attendees over a 3-month period: results of HB serologic tests; date and number of past anti-hepatitis B virus (HBV) immunization(s) (if any) according to health records; and the risk of STI and blood-transmitted infections (BTI). The study included 735 participants (age 27.9?±?9.2; 59.9% men). According to available health records (341 participants), 56.6% had received at least three and 67.2% at least one vaccine injection(s); 57.7% had received their last injection between 1994 and 1998, reflecting the strong vaccine policy during these years. Serologic testing (in 705 participants) showed evidence of a past or active HBV infection for 33 participants; of the remaining patients, 55.3% had anti-HBs antibody titers ≥10 IU/L. This rate was not higher in participants considered at risk for STI/BTI. Of the participants who received their last vaccine injection more than 15 years previously, 90.5% had anti-HBs antibody concentrations ≥10 and 60.3% ≥100 IU/mL. HB vaccination coverage is low in this population. Most of the vaccinated participants were immunized between 1994 and 1998, suggesting a failure of catch-up immunization of adolescents and at-risk adults. Long-term seroprotection persisted among vaccinated participants.     

Hepatitis B vaccination of immunosuppressed heart transplant recipients with the vaccine Hepa Gene 3 containing pre-S1, pre-S2, and S gene products

The antibody response of immunosuppressed heart transplant recipients to vaccination with the hepatitis B (HB) virus vaccine Hepa Gene 3 (HG-3), containing HB virus pre-S1, pre-S2, and S gene products, was examined. Three heart transplant recipients who had been vaccinated preoperatively against HB responded well to the vaccination. Five of 38 patients (13.2%) vaccinated postoperatively before HG-3 vaccination with the second-generation vaccine Gen-H-B-Vax-D (37 without and 1 with detectable anti-HBs response) and 3 of 24 (12.5%) without previous HB vaccination developed protective anti-HBs titers (greater than 10 U/1) after immunization with the HG-3 vaccine. The l low response rate (8/62, 12.9%) found for postoperatively vaccinated patients indicates that heart transplant recipients should be vaccinated against HB before immunosuppressive medication.Abbreviations HB hepatitis B - HG-3 Hepa gene 3     

Simultaneous administration of hepatitis B and yellow fever vaccines

In most developing countries, hepatitis B prevention is carried out early in life. In these countries, mobile immunization teams have a limited number of sessions to devote to each rural community; simultaneous administration of multiple antigens is thus normal practice. We compared the immune responses of Senegalese children to the separate or simultaneous injections of yellow fever and hepatitis B vaccines. Injections were given at the time of booster injection for hepatitis B vaccine. Yellow fever antibodies were detected in similar proportions in infants immunized with either yellow fever vaccine alone or yellow fever and hepatitis B vaccines simultaneously. However, a lower proportion of high yellow fever antibody levels were observed when the two vaccines were injected simultaneously. No reduction in the anamnestic response of antibodies against the surface antigen of hepatitis B virus (anti-HBs) was observed when yellow fever vaccine was injected at the same time as the booster dose of hepatitis B vaccine. Since no untoward reactions were noted, it is concluded that hepatitis B and yellow fever vaccines can be administered at the same time.     

Enhanced immunogenicity and protective effect conferred by vaccination with combinations of modified vaccinia virus Ankara and licensed smallpox vaccine Dryvax in a mouse model

Significant adverse events are associated with vaccination with the currently licensed smallpox vaccine. Candidate new-generation smallpox vaccines such as the replication-defective modified vaccinia virus Ankara (MVA) produce very few adverse events in experimental animals and in limited human clinical trials conducted near the end of the smallpox eradication campaign. Efficacy evaluation of such new-generation vaccines will be extraordinarily complex, however, since the eradication of smallpox precludes a clinical efficacy trial and the correlates of protection against smallpox are unknown. A combination of relevant animal efficacy studies along with thorough comparative immunogenicity studies between traditional and new-generation smallpox vaccines will be necessary for vaccine licensure. In the present study, a variety of immune responses elicited by MVA and the licensed smallpox vaccine Dryvax in a murine model were compared, with a focus on mimicking conditions and strategies likely to be employed in human vaccine trials. Immunization of mice with MVA, using several relevant vaccination routes including needle-free delivery, elicited humoral and cellular immune responses qualitatively similar to those elicited by vaccination with Dryvax. Similar levels of vaccinia-specific IgG and neutralizing antibody were elicited by Dryvax and MVA when higher doses (approximately 1 log) of MVA were used for immunization. Antibody levels peaked at about 6 weeks post-immunization and remained stable for at least 15 weeks. A booster immunization of either MVA or Dryvax following an initial priming immunization with MVA resulted in an enhanced IgG titer and neutralizing antibody response. In addition, both Dryvax and various MVA vaccination protocols elicited antibody responses to the extracellular enveloped form of the virus and afforded protection against a lethal intranasal challenge with vaccinia virus WR.     

The immune response of healthy Nigerian adults to small doses of hepatitis B vaccine: comparison of 10- and 20-micrograms doses

The immunogenic effect of hepatitis B vaccine (H-B-vax) was evaluated in 120 seronegative healthy Nigerians. Three doses of the vaccine were given at 0, 1, and 6 months. Serial blood samples were tested 1 month after each vaccination for hepatitis B surface antibody (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc). Of 60 vaccines given 20 micrograms of the vaccine, 40% had significant anti-HBs response 1 month after the first dose, 70% after the second dose, and 91.7% after the third dose. In the 60 vaccines given 10-micrograms doses, the seroconversion rates were 35, 73.3, and 90%, respectively. It is concluded that this vaccine in 10-micrograms doses is as effective as the larger doses in producing anti-HBs. The administration of small doses would reduce the cost of large-scale vaccination programs in developing countries.