吸附无细胞百白破联合疫苗的安全性和免疫原性研究

目的评价某公司研制的吸附无细胞百白破联合疫苗(DTaP)的安全性和免疫原性。方法选择1 200名3~5月龄知情同意、无百白破疫苗接种史、无百日咳白喉破伤风病史、无百白破疫苗接种禁忌症的健康婴幼儿,按1∶1比例随机接种3针次试验疫苗和对照疫苗,每针次间隔1个月。在观察期内对受试者进行安全性观察,采集免前和全程免疫后第28d血清样本,进行免疫原性观察。结果免疫后试验组抗百日咳毒素(PT)、丝状血凝素(FHA)、白喉类毒素(DT)、破伤风类毒素(TT)抗体阳转率均99%,与对照组相比,差异均无统计学意义(P值均0.05),试验组非劣效于对照组。4种抗体几何平均浓度(GMC)试验组均高于对照组(P值均0.01);抗体几何平均增长倍数(GMFI)除PT抗体外,其他3种抗体水平试验组均高于对照组(P值均0.05)。两组全身和局部不良反应均以1级和2级为主,3级不良反应发生率均2%,仅疲倦乏力、肿、疼痛等发生率试验组(2.17%~6.17%)高于对照组(0.67%~3.50%)(P值均0.05)。结论该公司研制的吸附无细胞百白破联合疫苗与同类上市疫苗相比,免疫原性较好,不良反应轻微,安全性可以耐受,可进一步进行多联疫苗探索和研究。     

两种吸附无细胞百白破联合疫苗安全性及免疫原性对比研究

20世纪70年代末,日本Sato首先研制出吸附无细胞百白破联合疫苗(DTaP),经大规模临床观察,证明较少出现严重副反应,已在欧美等国家推广使用[1,2]。我国于1993年研制成功DTaP,经观察证实,接种后全身反应和局部反应轻微,免疫效果好[3,4],但目前国内生产的DTaP远不能满足需求。浙江天元生物药业股份有限公司采用纯化工艺去除容易引起不良反应的百日咳内毒素,研制出DTaP。为探讨该公司所产的DTaP安全性和免疫原性,论证其生产与推广的可行性,根据国家药品监督管理局有关要求,于2006年9月~2007年4月进行了现场试验工作,现将结果报告如下。1材…     

无细胞百白破联合疫苗安全性和免疫原性研究

[目的]评价长春长生生物科技股份有限公司研制的吸附无细胞百白破联合疫苗的安全性和免疫原性。[方法]在江苏省连云港市赣榆县选择3~5月龄、未接种过百白破联合疫苗、无百日咳白喉破伤风疾病史的足月健康儿童进行临床研究,采用随机、双盲、同类疫苗平行对照设计,将观察对象按3︰2的比例随机分别接受观察疫苗和对照疫苗的接种。在观察期内对接种对象进行安全性观察,接种前后采集血清样本,进行免疫原性的观察。[结果]受试者全身中度发热反应发生率为1.62%（15/924）,没有出现全身严重及以上反应。未出现中度以上局部反应。免疫原性结果表明：受试者破伤风抗毒素阳转率为100.00%;白喉抗毒素阳转率为98.05%;抗百日咳毒素抗体阳转率为87.99%,抗丝状血凝素抗体阳转率为93.18%。[结论]该疫苗接种后具有低反应性和较好的免疫原性。     

三组分的无细胞百白破联合疫苗安全性和免疫原性研究

葛兰素史克公司的吸附无细胞百白破联合疫苗 ,采用了分别提取百日咳毒素 (PT)、丝状血凝素 (FHA)、6 9kD外膜蛋白 (PRN ,粘附素 )三种抗原后 ,再按照各自的含量配合制备而成。为考察该疫苗的安全性和免疫原性 ,在广西壮族自治区横县选择 3～ 6月龄、足月分娩、未接种过百白破联合疫苗的健康婴儿进行了临床研究。安全性结果表明 :受试者全身中反应发生率为 1 2 % (17人次 / 1386人次 ) ,弱反应发生率为 11 5 % ,无强反应发生。受试者局部淋巴结无异常反应 ,注射部位弱反应发生率为 0 5 % (7人次 / 1386人次 ) ,无中、强反应发生。免疫原性结果为 :受试者白喉抗体阳转率为 99 2 % ;破伤风抗体阳转率为 99 2 % ;抗PT抗体的阳转率为 96 4 % ;抗百日咳FHA抗体的阳转率为 99 3% ;抗粘附素抗体水平免疫后比免疫前增长≥ 4倍的占 94 5 %。结果证明 :该疫苗接种后具有低反应性和良好的免疫原性。     

吸附无细胞百白破联合疫苗安全性观察

目的探讨吸附无细胞百白破联合疫苗的安全性。方法对600名3个月~6周岁足月出生的健康儿童,以2∶1的比例按照计划免疫程序随机分别接种试验疫苗和对照疫苗,进行安全性观察。结果发热反应总发生率为15.38%(178/1159),其中2 3级反应率为3.28%(38/1159)。局部反应发生率疼痛为0.60%(7/1159),其中2和3级反应率为0.26%(3/1159),红为l.12%(13/1159),肿为0.78%(9/1159),其中2和3级反应率为0.09%(1/1159),所有受试者在观察期内均未观察到4级(潜在的生命危胁)不良反应。结论试验用吸附无细胞百白破联合疫苗对3月龄及其以上人群具有较好的安全性。     

两种吸附无细胞百白破联合疫苗基础免疫的安全性及免疫原性对比研究

[目的]通过观察两种无细胞百白破联合疫苗(DTaP)预防接种的不良反应,并对比免疫前后抗体水平变化,获知试验组疫苗的安全性和有效性,作为推广疫苗依据.[方法]2007年12月～2008年4月,成都市青白江区疾病预防控制中心对分别注射两种DTaP的189名3～6月龄儿童进行接种反应观察,并采集血清样本进行检测.[结果]两种DTaP接种全身反应无明显差异;局部反应试验组红肿发生率(0%)小于对照组(0.54%),试验组硬结发生率(1.65%)大干对照组(0%).两种DTaP接种不良反应均较低.试验组抗-PT、抗-FHA、抗-DT、抗-TT阳转率分别为87.9%、79.3%、99.1%、98.3%,免疫后保护率分别为:87.9%、79.3%、100%、100%;对照组抗-PT、抗-FHA、抗-DT、抗-TT阳转率分别为86.5%、78.4%、94.6%、91.9%,免疫后保护率分别为:86.5%、78.4%、100%、100%.两种DTaP阳转率、保护率均无明显差异(P>0.05).[结论]试验组DTaP不良反应较低,安全性好;免疫保护性较好,值得推广.     

吸附无细胞和全细胞百白破联合疫苗上市后预防接种安全性的比较分析

目的 评价中国(未包括香港、澳门特别行政区和台湾地区,下同)吸附无细胞百白破联合疫苗(Diphtheria Teta-nus and Acellular Pertusis Combined Vaccine,Absorbed;DTaP)和吸附全细胞百白破联合疫苗(Diphtheria,Tetanus andwhole-cell Pertusis Combined Vaccine,Absorbed;DTwP)上市后预防接种的安全性.方法 通过全国疑似预防接种异常反应(Adverse Events Following Immunization,AEFI)监测系统,收集10个试点省2005～2006年DTaP和DTwP严重不良反应监测数据,采用描述性方法对两种疫苗不良反应的发生特征进行比较分析.结果 中国DTaP和DTwP上市后,严重不良反应总发生率分别为3.5/10万剂和3.3/10万剂;DTaP以过敏反应为主,且第4剂反应危险性高;DTwP以无菌脓肿为主,高危险性反应剂次因反应的临床损害不同而异;部分疫苗品种和批号的反应存在聚集性,DTwP聚集性反应危险高于DTaP.结论 DTaP和DTwP上市后均具有较好的预防接种安全性;聚集性分析显示,DTaP安全性优于DTwP;需进一步加强对每批DTaP或DTwP上市前的质量控制.     

吸附无细胞百日咳-白喉-破伤风联合疫苗的安全性及免疫原性研究

目的评价北京天坛生物制品股份有限公司生产市售的吸附无细胞百日咳一白喉一破伤风联合疫苗（Absorbed Diphtheria,Tetanusand Acellular Pertussis Combined Vaccine;DTaP）,在儿童中应用的安全性和免疫原性。方法在浙江省4个县（市、区）,选择3235名3～5月龄的初次免疫儿童和3198名18～23月龄加强免疫儿童,按照免疫程序接种此次观察的DTaP,进行接种后安全性观察。采用间接血凝试验（Indirect Hemagglutination Test,IHA）测定白喉、破伤风抗体（Antibodyto Diphtheria,Anti—D;Antibody to Tetanus,Anti—T）,采用酶联免疫吸附试验（Enzyme．1inked Immunosorbent Assay,ELISA）检测抗百日咳毒素抗体（Antibody to Pertussis Toxin,Anti—PT）、抗丝状血凝素抗体（Antibodyto Filamentous Hemagglutinin,Anti—FHA）,计算抗体阳转率。结果此次DTaP基础免疫共观察9560剂次,加强免疫3198剂次。基础免疫和加强免疫的不良反应发生率分别为6．31％和14．57％,以轻度反应最多,未见严重不良反应及新的、罕见的不良反应。基础免疫3剂后,Anti-D、Anti—T阳转率均达100％,Anti-FHA和Anti-PT阳转率分别为46．02％和95．58％;加强免疫后Anti—D、Anti-T阳性率100％,Anti-FHA和Anti-PT阳性率分别为80．53％和90．27％。结论此次观察的DTaP有良好的安全性;基础免疫和加强免疫后,Anti-D、Anti—T阳转率和Anti—PT阳转率均达到较高水平,但Anti—F-HA阳转率不高。     

2018—2021年扬州市无细胞百白破联合疫苗预防接种安全性评价

目的：分析扬州市无细胞百白破联合疫苗（DTap）接种后出现疑似预防接种异常反应（AEFI）的发生特征及分布情况，为进一步评价DTaP疫苗预防接种的安全性提供依据。方法：通过中国免疫规划信息管理系统的AEFI监测系统收集2018年1月1日—2021年12月31日扬州市报告的DTaP疫苗相关AEFI个案数据，采用描述流行病学方法进行分析。结果：2018—2021年扬州市共接种DTaP疫苗365 215剂次，共报告DTaP疫苗相关AEFI个案1 055例，年均报告发生率为288.87/10万剂次，其中，一般反应1 015例，占96.21%，报告发生率为277.92/10万剂次，临床表现主要为发热、红肿、硬结；异常反应38例，占3.60%，报告发生率为10.40/10万剂次，主要为过敏性皮疹和荨麻疹；偶合症最少，共2例，占0.19%，报告发生率为0.55/10万剂次，均为热性惊厥；无心因性反应、疫苗质量事故及预防接种事故发生。9个县（市、区）各年度均有DTaP疫苗相关AEFI个案报告，其中，报告发生例数最多的为江都区，为232例；各月份均有DTaP疫苗相关AEFI个案报告，其中5、6、7月份报...     

接种无细胞百白破疫苗偶合Citrin缺陷症一例报告

1疫苗接种史患儿,男,2008年11月3日出生,第2胎,出生体重3.3kg,足月剖宫产。2009年3月10日,患儿在五峰县某预防接种门诊经接种医生询问健康状况后注射B型流感嗜血杆菌结合疫苗(简称Hib疫苗、兰州生物制品厂生产,批号:20080901,有效期至2010-09-14,左侧大腿外侧肌肌注)、     

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.     

流行性感冒灭活亚单位疫苗和裂解疫苗的安全性和免疫原性的比较研究

目的：比较流感亚单位疫苗与裂解疫苗的安全性和免疫原性。方法：流感亚单位疫苗和裂解疫苗按随机双盲法分别接种249名和250名6～12岁健康儿童。于接种当日和接种后3天内观察局部反应和全身反应。用血凝抑制试验检测接种儿童免疫前后的血凝抑制抗体(HI)滴度，计算抗体4倍增长阳转率，免疫后的保护水平抗体(≥1：40)的免疫成功率，以及抗体几何平均滴度((GMT)值和增长倍数。比较流感亚单位疫苗和裂解疫苗的临床观察结果。结果：两种疫苗接种后均未见局部反应，发热反应率和中高度发热反应率亚单位疫苗低于裂解疫苗，两组的差异有显著的统计学意义。未见其他全身反应。对疫苗3个毒株的血清学检测结果显示：亚单位疫苗的阳转率为74．5％～95．1％，保护水平抗体的免疫成功率为94．2％～99．6％，抗体GMT增长倍数为5．4～21．2。裂解疫苗的阳转率为79．8％～97．8％，保护水平抗体的免疫成功率为96．4％～100．0％，抗体GMT、增长倍数为6．4～21．0。两种疫苗的免疫学效果相似，所见差异无显著的统计学意义。结论：流感亚单位疫苗和裂解疫苗接种6～12岁儿童后反应轻微，安全性良好，亚单位疫苗发热反应率低于裂解疫苗。两种疫苗的免疫原性良好，具有同样显著的免疫效果，可以推广使用。     

Comparison of the safety and immunogenicity of concomitant and sequential administration of an adult formulation tetanus and diphtheria toxoids adsorbed combined with acellular pertussis (Tdap) vaccine and trivalent inactivated influenza vaccine in adults

The annual contact for influenza vaccination provides an opportunity to ensure that adults have received other recommended vaccines such as Tdap. Healthy 19-64 year-olds were randomized to receive concomitant administration of Tdap and influenza vaccines or influenza vaccine followed (in 4-6 weeks by) Tdap. 720 participants were enrolled. No clinically relevant between-group differences were observed in the rates or severities of erythema, swelling, or pain at the Tdap injection site. Injection-site pain was the most commonly reported adverse event (66.6% concomitant administration group versus 60.8% sequential administration group); most pain was graded as mild and resolved by day 3. Seroprotection and seroresponse rates for all influenza strains were comparable between the two groups. For diphtheria and tetanus, seroprotection rates and post-vaccination GMTs were non-inferior in the concomitant administration group compared to the sequential administration group. A trend for lower antibody responses to pertussis antigens PT, FHA, and FIM was observed after concomitant administration and, for PRN, this difference failed the non-inferiority criteria. While there is a small diminution in antibody response to tetanus and pertussis antigens, concomitant administration of Tdap and influenza vaccine was well tolerated and immunogenic and may offer practical advantages including convenience, compliance, and cost-savings.     

冻干麻疹-腮腺炎-风疹三联活疫苗免疫安全性及免疫学效果观察

目的 观察卫生部北京生物制品研究所研制的麻疹-腮腺炎-风疹（北京MMR）疫苗的免疫学效果。方法 分别选择10-12岁，2-2.5岁和8-12月龄儿童，接种北京MMR（实验疫苗），并与进口MMR疫苗，麻疹疫苗，腮腺炎疫苗和风疹疫苗（对照疫苗）相比较，开展该疫苗的免疫安全性和免疫原性观察研究。结果 在32名2岁以上较大龄儿童接种北京MMR疫苗无副反应发生后，对104名8-12月龄婴儿接种该疫苗，仅有6.7%和1.9%的儿童分别发生一过性发热（中低反应）和皮疹，无其他不良反应发生，北京MMR疫苗免疫接种后，其麻疹，风疹，腮腺炎HI抗体阳转率分别为100%，100%和85.7%;GMT分别为41，320和6.1，分别与对照疫苗相比，差异多无显著性。结论 北京MMR疫苗具有与目前使用的麻疹疫苗，腮腺炎疫苗，风疹疫苗及进口MMR疫苗相同的免疫安全性和免疫原性，且可以作为麻疹的基础免疫和复种疫苗使用。     

41例吸附无细胞百白破疫苗疑似预防接种异常反应的监测分析

目的分析吸附无细胞百白破疫苗(adsorbed acellular DTP combined vaccine,DTaP)疑似预防接种异常反应(adverse events following immunization,AEFI)影响因素,完善疑似预防接种异常反应管理。方法针对2011年1月-2014年12月在本院航海东路社区卫生服务中心接种DTaP发生AEFI 41例进行回顾性监测分析。结果同期DTaP共接种3月龄~2周岁的儿童28 494人,发生AEFI 41例,发生率为0.144%。通过4年来接种DTaP发生AEFI监测数据进行对比,4年间AEFI呈整体下降趋势,差异有统计学意义(χ2=8.614,P=0.035)。结论数据显示,AEFI全年各月份均有出现,以7月、8月居多,呈现出夏季高发的态势,多发生在第3针或第4针。AEFI发生与DTaP疫苗本身固有特性、儿童年龄、接种剂次、接种季节时间、接种技术等相关。因此通过在接种DTaP时要严格规范化安全操作,掌握接种禁忌证,尤其注意AEFI的高发时机,做好接种告知提醒,可以从最大程度上减少AEFI发生。     

Reactogenicity and immunogenicity of a double-strength acellular pertussis vaccine.

The reactogenicity and immunogenicity of a double-strength acellular pertussis vaccine were evaluated after administration to 16 4-6-year-old children. The vaccine contained toxoided lymphocytosis-promoting factor (6.0 micrograms/dose), filamentous haemagglutinin (70 micrograms/dose), agglutinogens (1.4 micrograms/dose) and the 69 kDa protein (approximately 8.0 micrograms/dose). The vaccine was extremely well tolerated with few minor side effects following immunization. Significant increases in antibodies to all pertussis vaccine components were noted. In summary, this double-strength acellular pertussis vaccine, containing a very high dose of filamentous haemagglutinin, had minimal reactogenicity and was immunogenic. These findings, as well as other studies with this vaccine, indicate that filamentous haemagglutinin is not a major determinant of vaccine reactogenicity.     

An acellular pertussis vaccine in healthy adults: safety and immunogenicity. Pennridge Pediatric Associates.

Recent data indicate that Bordetella pertussis can be an important cause of illness in adolescents and adults. In a randomized observer- and subject-blinded study, adults (> or = 18 years of age) received an acellular pertussis (aP) vaccine containing genetically inactivated pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN), or a saline placebo, and were monitored for safety and immunogenicity. IgG antibodies to PT, FHA, and PRN were measured by enzyme-linked immunosorbent assay (ELISA) and PT neutralization by a Chinese hamster ovary (CHO) cell assay. Local reactions, more common in the aP group, were mild and transient. One month after immunization, geometric mean ELISA antibody concentrations for the aP and placebo groups, respectively, were: anti-PT, 463 and 7.6; anti-FHA, 417 and 18; and anti-PRN, 855 and 14. The anti-PT neutralization titers for the aP and placebo groups were 1:3439 and 1:58 respectively. This aP vaccine is a safe and immunogenic candidate booster vaccine against pertussis for adults.     

A Japanese study to assess immunogenicity and safety of a typhoid Vi polysaccharide vaccine

BackgroundAlthough typhoid fever is rare in Japan, imported cases have been reported occasionally in travelers returning from endemic areas. To achieve licensing of a typhoid Vi polysaccharide vaccine (Typhim Vi^®) and make it widely available in Japan, this study was conducted at the request of the Japanese Ministry of Health Labor and Welfare to assess the immunogenicity and safety of this vaccine when given as a single dose (the recommended schedule of administration) in a Japanese population.MethodsIn this multi-center, open-label, non-comparative, intervention study performed in Japan, 200 healthy volunteers (188 adults [≥18 years of age], 7 adolescents [12–17 years of age] and 5 children [2–11 years of age]) were administered Typhim Vi^®. Immunogenicity was assessed 28 days after vaccinations using an ELISA method of anti-Vi antibody detection. A 4-fold increase in anti-Vi titer was considered as the threshold for seroconversion for anti-Vi antibodies. Safety was assessed up to 28 days following vaccination.ResultsOverall, 92.0% (95% confidence interval [CI]: 87.3–95.4%) of participants achieved seroconversion 28 days after a single dose of typhoid Vi polysaccharide vaccine. GMTs of Vi antibody titers increased from 6.6 (95% CI: 5.8–7.4) prior to vaccination to 157.3 (95% CI: 135.1–183.2) on Day 28 after vaccination. The geometric mean of individual anti-Vi antibody titer ratios (Day 28/Day 0) was 23.9 (95% CI: 20.3–28.3). There were no immediate adverse events and no adverse events led to the discontinuation of participants from the study. Across all age groups, pain and myalgia were the most frequently reported injection site and systemic reactions, respectively. Most of these reactions were mild in intensity and resolved within 7 days.ConclusionsA single dose of typhoid Vi polysaccharide vaccine, Typhim Vi^®, demonstrated good safety and immunogenicity profile in a Japanese population.     

流感疫苗安全性和免疫效果观察

[目的 ]　评价流行性感冒疫苗 (防感灵TM)接种后的安全性和抗体阳转情况。 [方法 ]　采用随机和双盲法选择接种组和对照组 ,分别接种流感疫苗和伤寒Vi疫苗。接种后 3天内进行安全性观察。同时 ,免后 4个月时采集静脉血检测流感血凝抑制抗体的产生情况。 [结果 ]　接种组一般副反应率为 1.70 % ,全身副反应率为0 .6 4% ,与对照组差异无显著性。A1、A3、B型的血凝抑制抗体阳转率分别为 97.7%、99.2 %和 82 .9% ,接种组GMT均明显高于对照组。 [结论 ]　流感疫苗 (防感灵TM)安全性良好 ,并且有较好的免疫原性