百白破混合制剂免疫持久性研究

70~80年代末,在观察基地比较吸附DPT间隔1月、2月接种2针和未吸附DPT接种3针、2针的免疫效果和免疫持久性,经血清学效果测定表明,四组儿童基免后能产生良好的白喉、破伤风抗体应答,而接种非吸附DPT儿童的百日咳抗体产生较差。加免后,三种抗体明显上升,白喉抗体至少可持续8年,破伤风抗体可维持5年左右,而百日咳抗体仅能维持3年左右。另对吸附DPT间隔2月接种2针与未吸附DPT接种3针比较,基免后白喉、破伤风、百日咳三种抗体均以吸附DPT效果较好,加免后则无显著差异。     

Adequate immune response to tetanus toxoid and failure of vitamin A and E supplementation to enhance antibody response in healthy children

The effects of vitamin A and vitamin E supplementation on the IgG response to tetanus toxoid after primary immunization were evaluated in a prospective, randomized controlled clinical trial involving 89 healthy infants with normal serum vitamin A and E levels at 2 months of age. Before the first dose of DPT vaccine, the infants were randomly enrolled into four different study groups [Group I (n=24): 30,000 IU vitamin A for 3 days just after each three doses of primary vaccination, Group II (n=21): 150 mg oral vitamin E for only 1 day after the injections for primary immunization, Group III (n=21): vitamins A and E together in the same order, Group IV (n=23) no vitamin after DPT vaccines]. Serum tetanus antitoxin (IgG) titres were measured three times; initially at 2 months of age before the first dose of DPT, secondly at 5 months of age 1 month after primary immunization and thirdly at 16-18 months of age before the booster dose of DPT. Before the first dose of the DPT vaccine, 1 month after the third DPT injection and at 16-18 months before the booster dose of DPT, there was no significant difference in serum tetanus antitoxin levels between these four groups. A significant increase was observed in all the groups when serum tetanus antitoxin levels before (2 months) and after (5 months) primary immunization were compared. In addition, serum antibody levels against tetanus significantly decreased in the four groups before booster vaccination. Before the beginning of primary immunization, 15 infants (16.8%) had serum tetanus antitoxins (IgG) below protective level. After three doses of DPT, all the infants had protective antitoxin levels. At 16-18 months of age before booster dose, four infants (10%) also had serum tetanus antitoxins (IgG) below the protective level. No side-effects were observed except bulging fontanelle in two infants in Group I.     

2015年新建县948例入园儿童计划免疫效果评价

目的 了解入园儿童接种乙型肝炎(乙肝)、脊髓灰质炎(脊灰)、百日咳、白喉、破伤风疫苗(以下简称“五防”疫苗)后抗体阳性率与疫苗“首针及时接种率、全程接种率、全程及时接种率”的吻合程度,评价儿童预防接种效果和免疫状况。方法 选取2015年新建县长堎地区新近入园的948例儿童作为研究对象,利用间接ELISA法检测血清标本中抗体阳性水平,通过查验儿童预防接种证收集预防接种信息,并进行比较分析。结果 948例入园儿童中,脊灰、百日咳、白喉、破伤风抗体阳性率均超过90%,乙肝抗体阳性率低于65%。除城镇儿童白喉、破伤风抗体阳性率显著高于农村(P<0.05)外,性别、户籍、居住地对“五防”疫苗的抗体阳性率影响不大(P>0.05)。全程接种乙肝、百白破三联疫苗的入园儿童乙肝、白喉、破伤风IgG抗体阳性率显著高于未全程接种者(P<0.05)。首针、全程是否及时接种“五防”疫苗对入园儿童这5种IgG抗体阳性率的影响不大(P>0.05)。结论 948例入园儿童脊灰、百日咳、白喉、破伤风免疫效果较好,而乙肝抗体阳性率相比较低。全程接种率相比首针及时接种率和全程及时接种率对评价儿童乙肝、白喉、破伤风疫苗免疫效果更有意义,值得关注并推广。     

成都市新生儿百日咳、白喉、破伤风胎传抗体水平调查

目的了解成都市新生儿百日咳、白喉、破伤风胎传抗体的水平及其变化情况。方法在4个区县对142名新生儿的脐血进行百日咳、白喉、破伤风抗体水平调查。结果百日咳抗体达到保护水平的率为1.41%,明显低于1988年的抗体水平(χ2=5.80,P0.05);白喉、破伤风抗毒素平均滴度为0.3750和0.3537,其抗体达到保护水平的率分别为48.59%和52.11%,明显高于1988年的抗体水平(χ2=25.29,P0.05;χ2=63.49,P0.05)。结论该市新生儿百日咳、白喉、破伤风胎传抗体水平达不到有效的保护,应重视新生儿父母、与年龄较小儿童接触和其他适合接种白破疫苗的成人的免疫接种,以保护新生儿免受此类疾病的感染。     

Recombinant cholera toxin B subunit (rCTB) as a mucosal adjuvant enhances induction of diphtheria and tetanus antitoxin antibodies in mice by intranasal administration with diphtheria-pertussis-tetanus (DPT) combination vaccine

Recombinant cholera toxin B subunit (rCTB) which is produced by Bacillus brevis carrying pNU212-CTB acts as a mucosal adjuvant capable of enhancing host immune responses specific to unrelated, mucosally co-administered vaccine antigens. When mice were administered intranasally with diphtheria-pertussis-tetanus (DPT) combination vaccine consisting of diphtheria toxoid (DTd), tetanus toxoid (TTd), pertussis toxoid (PTd), and formalin-treated filamentous hemagglutinin (fFHA), the presence of rCTB elevated constantly high values of DTd- and TTd-specific serum ELISA IgG antibody titres, and protective levels of diphtheria and tetanus toxin-neutralizing antibodies but the absence of rCTB did not. Moreover, the addition of rCTB protected all mice against tetanic symptoms and deaths. DPT combination vaccine raised high levels of serum anti-PT IgG antibody titres regardless of rCTB and protected mice from Bordetella pertussis challenge. These results suggest that co-administration of rCTB as an adjuvant is necessary for induction of diphtheria and tetanus antitoxin antibodies on the occasion of intranasal administration of DPT combination vaccine.     

深圳市健康人群白喉百日咳破伤风抗体水平监测

目的了解深圳市健康人群白喉、百日咳、破伤风抗体水平和百日咳-白喉-破伤风联合疫苗（Diphtheria,Tetanus,Pertussis Combined Vaccine：DPT）的免疫效果,为制订DPT免疫策略提供依据。方法百日咳抗体检测采用微量凝集试验法,白喉、破伤风抗体检测均采用间接血凝试验法。结果检测的650人中,白喉抗体阳性率为88．31％,保护率为87．38％,几何平均浓度（Geometric Mean Concentration,GMC）为0．2595IU／ml（国际单位／毫升）;破伤风抗体阳性率为71．54％,保护率为64．15％,GMC为0．5607IU／ml;百日咳抗体阳性率为92．77％,保护率为37．23％,几何平均滴度为1：156．87。结论儿童完成DPT基础免疫后,1．5-2岁DPT加强免疫和小学一年级学生白喉．破伤风联合疫苗（Diphtheria,Tetanus Combined Vaccine;DT）加强免疫收到了良好的效果。因抗体水平随着年龄的增长呈下降的趋势,〉10岁以后抗体明显下降,故需对初中一年级学生、高中三年级学生或大学新生、成人接种降低抗原含量的DT进行加强免疫。     

2010年白山市健康人群百日咳、白喉及破伤风IgG抗体水平监测

目的了解白山市健康人群百日咳、白喉、破伤风血清抗体水平。方法在全市6个县(市、区)采取随机抽样的方法抽取八道江区,对0～1岁、1～2岁、3～4岁、5～6岁、7～14岁、15～19岁、﹥20岁7个年龄组的健康人群进行抗体水平监测。结果百日咳IgG抗体阳性率为80.0%,白喉IgG抗体阳性率为68.10%,新生儿破伤风IgG抗体阳性率为49.52%。不同年龄组人群百日咳、白喉、破伤风抗体阳性率比较,差异有统计学意义(P﹤0.05)。结论在进一步提高常规免疫接种率的基础上,加强人群免疫水平监测,考虑对成人进行加强免疫[1]。     

Immunogenicity of a combined diphtheria-tetanus-acellular pertussis vaccine in adults

Two clinical studies were undertaken to evaluate the immunogenicity of an adult-type dTpa booster vaccine (Boostrix by GlaxoSmithKline Biologicals). Blood samples taken prior to vaccination showed that 24.4 and 13.0% of subjects were seronegative for diphtheria and tetanus antibodies, respectively. Moreover, about one-third of the vaccinees had no detectable levels of antibodies to pertussis toxoid (PT) or pertactin (PRN). One month post-vaccination, more than 93% of all individuals, regardless of age or type of vaccine received, had seroprotective antibody levels for diphtheria and tetanus (> or = 0.1IU/ml). In those individuals vaccinated with the adult-type dTpa vaccine (Boostrix), more than 98% were found to be seropositive for antibodies to all three pertussis antigens (PT, filamentous haemogluttin (FHA), and PRN). These data suggest that immunity to diphtheria, tetanus and pertussis (DTP) in adults wanes and that booster vaccination with an adult-type combined dTpa vaccine would boost the serological response to diphtheria antitoxin, tetanus antitoxin and antibodies to Bordetella pertussis PT, FHA and PRN.     

2010年湖北省部分地区健康人群百日咳、白喉、破伤风人群免疫水平分析

目的了解湖北省人群免疫状况,评价预防接种质量和效果,制定免疫对策。方法分七个年龄组抽取黄石和咸宁两个地区部分健康人群,采用ELISA法定量检测正常人血清中百日咳、白喉和破伤风IgG抗体水平。结果两个地区健康人群中,百日咳IgG抗体阳性率为27.14%,白喉和破伤风IgG抗体安全保护率分别为55.71%和60.29%。结论抽取的湖北省两个地区健康人群百日咳、白喉和破伤风IgG抗体阳性率均比较低,提示要扩大接种覆盖率,缩短强化免疫周期,提高冷链运转效率和疫苗接种质量。     

湖北省2009年健康人群百日咳、白喉、破伤风抗体水平监测分析

目的:为了解湖北省2009年健康人群血清中百日咳、白喉和破伤风抗体水平,抽样评价预防接种质量。方法:分七个年龄组抽取黄冈地区、咸宁地区、宜昌市和十堰市四个地区部分健康人群,采用间接ELISA法(定量)检测健康人群血清中百日咳、白喉、破伤风IgG抗体水平。结果:四个地区健康人群中,百日咳、白喉、破伤风IgG抗体阳性率分别为34.5%5、9.3%和62.2%。结论:湖北省四个地区健康人群百日咳、白喉、破伤风抗体保护率比较低,提示我们要扩大接种覆盖率,提高冷链运转效率和疫苗接种质量。     

Persistence of antibodies 3 years after booster vaccination of adults with combined acellular pertussis, diphtheria and tetanus toxoids vaccine

The duration of protection after vaccination with reduced antigen content diphtheria, tetanus and acellular pertussis vaccines (Tdap) is not known. Long-term post-vaccination serological data will help to improve understanding of the duration of humoral immunity and guide vaccination policy for the timing of repeat dose administration. The persistence of antibodies to Tdap antigens was measured 3 years after vaccination of adults 19-64 years of age with one of 2 Tdap vaccines (Boostrix^®, GlaxoSmithKline Biologicals; Tdap-B: or Adacel^®, Sanofi Pasteur; Tdap-A). In both groups, geometric mean concentrations for antibodies to diphtheria, tetanus, and pertussis vaccine antigens were decreased at year 3 relative to levels observed 1 month and 1 year following vaccination, but remained higher than pre-vaccination levels. Seroprotection rates for diphtheria and tetanus remained high for both Tdap vaccines (for diphtheria, 96.9% and 97.8% for the Tdap-B and Tdap-A groups, respectively; for tetanus, 98.1% and 99.6%, respectively).     

2011年湖北省麻城市健康人群百日咳、白喉、破伤风抗体水平调查

目的调查评估麻城市2011年健康人群中百日咳、白喉和破伤风抗体水平。方法随机抽取健康人群血清480人份,分为六个年龄组,采用ELISA法检测百日咳IgG、白喉IgC和破伤风IgG。结果百日咳IgG、白喉IgG和破伤风IgG保护率分别为21．04％、73．33％和67．71％。3-6岁与7-14岁白喉抗体保护率分别为90％和76．67％,两年龄段抗体保护率差异有统计学意义（X^2=29．73,P〈0．01）;3-6岁与7-14岁破伤风抗体保护率分别为93．33％和66．67％,两年龄段抗体保护率差异有统计学意义（X^2=40．52,P〈0．01）。结论麻城市人群中百日咳抗体水平较低,6岁以后人群中白破抗体水平下降明显。     

A randomised controlled trial with a diphtheria-tetanus-acellular pertussis (dTpa) vaccine in adults

The aim of this assessor-blinded trial was to compare the immunogenicity and reactogenicity of a candidate diphtheria, tetanus toxoids and acellular pertussis vaccine with reduced antigen content for diphtheria and pertussis (dTpa) with a licensed reduced adult-type diphtheria-tetanus vaccine Td (reduced diphtheria content) and with an experimental candidate monovalent acellular pertussis vaccine with reduced antigen content (pa). The dTpa and pa vaccines had identical pertussis antigen content. A total of 299 healthy adults (> or =18 years, mean age: 30.1 years+/-10.7) were randomised into 3 groups to receive a single dose of one of the study vaccines. In all groups, clinically significant reactions (severe) were infrequent (0-6%) and no serious adverse events were reported during the study. The incidence of local and systemic reactions following the administration of dTpa was comparable to the Td vaccine group. Of the total study group, prior to vaccination 52. 3 and 93.2% of the subjects had anti-diphtheria and anti-tetanus antibody levels > or = 0.1 IU/ml, respectively; and 73.1, 98.2 and 74.5% of the subjects were seropositive for pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) antibodies, respectively. One month after vaccination, a similar percentage of subjects in the dTpa and Td groups had anti-diphtheria (88.4% vs 90. 1%) and anti-tetanus (100% vs 98.9%) antibody levels > or =0.1 IU/ml. Similar anti-FHA (100%) and anti-PRN (98.9%) vaccine response rates were seen in the dTpa and pa groups, while the anti-PT vaccine response rates were 96.8 and 100.0%, respectively. The dTpa vaccine is as well tolerated and immunogenic as the licensed Td vaccine, and additionally, can also boost antibodies against pertussis.     

Immunogenicity of reduced antigen content tetanus-diphtheria-acellular pertussis vaccine in adolescents as a sixth consecutive dose of acellular pertussis-containing vaccine

Three hundred and nineteen adolescents aged 10-12 years who had been previously vaccinated with five doses of acellular pertussis-containing vaccines received single doses of Tdap (reduced-antigen-content tetanus, diphtheria, acellular pertussis) and hepatitis A vaccines in a double-blind crossover trial. Long-term antibody persistence following vaccination with Tdap at pre-school age was similar to that following vaccination with DTaP (diphtheria-tetanus-acellular pertussis). After the sixth dose booster, Tdap induced a vigorous immune response, consistent with protection against diphtheria, tetanus and pertussis diseases.     

深圳市南山区健康人群百日咳、白喉、破伤风抗体水平监测

目的了解健康人群百日咳、白喉和破伤风的免疫状况。方法随机抽查部分1～40岁健康人群进行百日咳、白喉和破伤风的抗体水平监测。结果百日咳抗体几何平均滴度1:77.63,抗体保护率21.97%;白喉、破伤风抗毒素平均滴度1.33IU/ml和0.73IU/ml,阳性率99.08%和81.92%。结论对百日咳、白喉和破伤风已经形成了较好的免疫屏障,但人群百日咳抗体水平偏低,应大力推广百白破联合疫苗。     

Immunogenicity and reactogenicity of a single dose of a diphtheria--tetanus--acellular pertussis component vaccine (DTaP) compared to a diphtheria--tetanus toxoid (Td) and a diphtheria toxoid vaccine (d) in adults

We compared immunogenicity and reactogenicity of a single dose of DTaP vaccine (containing tetanus and diphtheria toxoids and four acellular pertussis antigens) with conventional Td- or d-vaccines in 180 German adults. Antibody values against diphtheria and tetanus toxin and against the pertussis antigens fimbriae (FIM), filamentous hemagglutinin (FHA) and pertussis toxin (PT) were measured in pre- and post-immunization sera. Reactogenicity was determined by a patient diary card. Pre-immunization antibody values against diphtheria toxin were low in all three vaccine groups. After immunization, > or = 80% of the vaccinees in all three groups were fully protected (> or = 0.1 IU/ml), but geometric mean values were significantly higher in DTaP recipients compared to Td or d recipients (1.65 vs. 0.44 and 0.48, respectively; both P < 0.05). Pre-immunization antibody values against tetanus toxin were high in all three groups, and after immunization 100% of the vaccinees were protected (> or = 0.1 IU/ml). Furthermore, substantial antibody responses against pertussis antigens were elicited in DTaP recipients with geometric mean rises of 22.5, 4.1 and 7.5 for antibodies against FHA, fimbriae and PT, respectively. All three vaccines were well tolerated. Frequency and severity of local reactions were similar between DTaP and Td recipients and even less common in d recipients. Since DTaP did provide a significant boost of anti-pertussis antibodies and a significantly higher anti-diphtheria response than conventional Td vaccine without an increase of side effects, it might be an appropriate candidate for use in adults.     

Serological evaluation of poliomyelitis oral and inactivated vaccines in an urban low-income population at Rio de Janeiro, Brazil

Oral and inactivated poliomyelitis vaccines (OPV and IPV), were given to 160 children two months old, in a low income population at Rio de Janeiro. The vaccination was repeated 2 and 4 months later, always in association with diphtheria, tetanus and pertussis (DPT) vaccine. Blood specimens were collected before vaccination at the time of the third dose of vaccine and later at the time of measles vaccination, when the children were nine months old. The serological response to two doses of IPV showed high titres of antibody in all but one child and 100% conversion after three doses. Although poliomyelitis has been controlled in Brazil by the use of OPV in large mass campaigns, the results obtained with IPV support the possibility of its use in the basic immunization schedule, providing lower costs could be achieved for the inactivated vaccine.     

An adolescent-adult formulation tetanus and diptheria toxoids adsorbed combined with acellular pertussis vaccine has comparable immunogenicity but less reactogenicity in children 4-6 years of age than a pediatric formulation acellular pertussis vaccine and diphtheria and tetanus toxoids adsorbed combined with inactivated poliomyelitis vaccine

In Canada, the fifth dose of the routine childhood immunization schedule against diphtheria, tetanus, pertussis and polio is given at 4-6 years of age. Up to 30% of children may have significant local reactions (redness, swelling) and this may be related to pertussis and diphtheria antigen content. We sought to determine if a combination product with lower content of pertussis and diphtheria toxoids (dTap) would result in fewer local reactions and not have inferior immunogenicity to a combination vaccine with higher pertussis and diphtheria content (diphtheria-tetanus-acellular pertussis-inactivated polio virus, DTaP-IPV). Healthy children aged 4-6 years with complete primary immunization series and a fourth dose of diphtheria and tetanus toxoids component pertussis inactivated polio and Haemophilus influenzae type B conjugate vaccine were randomized to one dose of dTap, followed in 4-6 weeks by one dose of IPV or control DTaP-IPV. Immediate reactions within 30 min, solicited injection site and systemic reactions within 14 days, and unsolicited adverse events (AE) within 6 weeks post-vaccination were monitored. Serum was collected prior to immunization, and 4-6 weeks after vaccine for diphtheria, tetanus and pertussis antibodies (Ab). Sample size was designed to detect > or =10% difference in injection site erythema, pain or swelling between groups 593 children at eight Canadian sites completed the study; no participant withdrew because of an AE. All safety endpoints on days 0-14 were less frequent in children randomized to the dTap than DTaP-IPV group: erythema (34.6% versus 51.7%), swelling (24.2% versus 33.8%) and pain (39.6% versus 67.2%). Fever was also less common (8.72% versus 16.9%). All children in both study groups had seroprotective Ab levels to diphtheria and tetanus at 4-6 weeks (> or =0.10 IU/mL). The majority of children in each vaccine arm had a four-fold increase in pertussis antibodies. Fever and injection site reactions are less common in 4-6 year-old-children who receive a dTap vaccine compared to DTaP-IPV, without inferior immunogenicity.     

吸附精制百白破混合制剂两针接种的血清学效果免疫持久性观察

预防百日咳、白喉、破伤风的方法是注射百白破混合制剂,共注射三针,吸附制剂注射两针,每针间隔一个月。于1978~1984年在江苏省东海县应用吸附精制百白破混合制剂进行两针注射观察。经血清学效果测定表明:白喉、破伤风、百日咳三种抗体均显著上升,且达到保护水平以上,百日咳抗体仅能维持六个月左右,一年后大多数低于保护水平,但经加强免疫后又能达到保护水平以上。基免三年至五年结果表明,两针免疫后白喉和破伤风可产生满意的血清学效果,百日咳抗体水平上升尚可。     

A randomized,blinded, placebo-controlled trial comparing antibody responses to homeopathic and conventional vaccines in university students

BackgroundHomeopathic vaccines are licensed in many countries but scientific data to support their use are sparse. The goal of this study was to compare the antibody response of homeopathic and conventional vaccines and placebo in young adults. We hypothesized that there would be no significant difference between homeopathic vaccines and placebo, while there would be a significant increase in antibodies in those received conventional vaccines.MethodsA randomized blinded placebo-controlled trial was conducted where 150 university students who had received childhood vaccinations were assigned to diphtheria, pertussis, tetanus, mumps, measles homeopathic vaccine, placebo, or conventional diphtheria, pertussis, tetanus (Tdap) and mumps, measles, rubella (MMR) vaccines. The primary outcome was a ≥ two-fold increase in antibodies from baseline following vaccination as measured by ELISA. Participants, investigators, study coordinator, data blood drawers, laboratory technician, and data analyst were blinded.ResultsNone of the participants in either the homeopathic vaccine or the placebo group showed a ≥ two-fold response to any of the antigens. In contrast, of those vaccinated with Tdap, 68% (33/48) had a ≥ two-fold response to diphtheria, 83% (40/48) to pertussis toxoid, 88% (42/48) to tetanus, and 35% (17/48) of those vaccinated with MMR had a response to measles or mumps antigens (p < 0.001 for each comparison of conventional vaccine to homeopathic vaccine or to placebo). There was a significant increase in geometric mean titres of antibody from baseline for conventional vaccine antigens (p < 0.001 for each), but none for the response to homeopathic antigens or placebo.ConclusionsHomeopathic vaccines do not evoke antibody responses and produce a response that is similar to placebo. In contrast, conventional vaccines provide a robust antibody response in the majority of those vaccinated.Trial Registry: NCT 02825368.