冻干和液体甲肝减毒活疫苗接种安全性与免疫效果观察

为了解冻干和液体甲肝减毒活疫苗的接种安全性和免疫效果,在衢州市选择24~36月龄和18~25岁人群,分2组接种冻干和液体甲肝减毒活疫苗1针,观察免疫后48h内局部和全身反应,检测免疫后6周血清甲肝抗体阳转率和抗体滴度。结果显示:儿童和成人接种2种甲肝减毒活疫苗后,均未见有明显接种反应,疫苗安全性良好。冻干疫苗接种组和液体疫苗接种组,接种前甲肝抗体阳性率分别为20.41%和25.93%,两组间无显著性差异;接种后6周,甲肝抗体阳性率分别为95%和72.55%,抗体几何平均滴度(GMT)分别为160.85mIU/ml和48.56mIU/ml,接种后两组间抗体阳性率和GMT均有显著性差异,说明冻干疫苗较液体疫苗具有更好的免疫原性。     

疫苗上市后的监测结果评价

目的评价国家免疫规划疫苗上市后大规模应用的安全性、免疫效果和流行病学保护效果。方法采用主动监测和被动监测的方法观察疫苗上市后的安全性,采集适龄儿童甲肝疫苗免疫前后的血液标本进行抗体检测,采用1︰2病例对照研究进行甲肝、乙肝、结核和腮腺炎4种疫苗针对疾病的监测。结果 AEFI发生率居前三位的分别是麻疹风疹减毒活疫苗(18.81/10万)、乙脑减毒活疫苗(16.70/10万)和甲肝减毒活疫苗(12.71/10万);甲肝减毒活疫苗的免疫成功率为68%(34/50);共监测到1例乙肝病例,2例结核病例,126例流行性腮腺炎病例。结论中国疫苗安全性和甲肝疫苗的免疫效果较好,甲肝、乙肝疫苗的流行病学保护效果较好,卡介苗对肺结核的保护效果有限,含腮腺炎成分减毒活疫苗对腮腺炎的保护效果有待进一步研究。     

甲肝减毒活疫苗不同滴度的免疫效果评价

甲肝减毒活疫苗不同滴度的免疫效果评价方蕙，康来仪，潘启超，金子辰，郑晓虹，薛以乐，蒋清，张玮，张建民，程萍，沈菊华，万宗举预防和控制甲肝流行最有效的方法是接种甲肝疫苗。目前我国用于接种人体的甲肝减毒活疫苗的减毒株主要是Ｈ２和Ｌ－Ａ－１两株。从７０年代...     

甲型肝炎减毒活疫苗保护效果与应用策略研究

本研究课题旨在应用流行病学、免疫学及应用数学的原理及技术 ,考核我国自行研制的、国际上所独有的甲型肝炎(甲肝 )减毒活疫苗的免疫原性及保护效果 ,并研究符合我国国情的甲肝免疫预防策略。通过课题协作组近 10年的努力 ,我们确定了疫苗的规范化滴度 ;规范化甲肝减毒活疫苗的免疫原性 ,预防发病、感染与暴露后预防效果 ;对比了活疫苗与国外灭活疫苗的免疫原性以及单剂免疫与加强免疫的免疫原性 ;测定了活疫苗免疫后抗体持久性 ;改进了活疫苗滴度的测定方法 ;确定了甲肝疫苗的初免年龄 ,成人免疫效果 ,与免疫球蛋白联合免疫效果 ;测算了不…     

国产甲肝减毒活疫苗在部队战士中免疫效果观察

为了探索部队青年战士是否适用甲型肝炎疫苗,对甲肝预防提供科学依据。采用随机、双盲、安慰对照的设计,以ＥＬＩＳ必人群保护率为指标,观察国产甲肝减毒活疫苗的免疫效果。结果表明,免疫后３、６、１２、２４、３６个月时,疫苗组阳转率均显著高于对照组,而抗ＨＡＶ滴度在５个时点对照组均高于疫苗组,疫苗组无一例甲肝发生。表明国产甲肝减毒活疫苗免疫效良好,同样适合于成年人群使用。     

国产甲肝减毒活疫苗（H2株）在小学生中的免疫效果研究

目的: 研究国产甲肝减毒活疫苗 (H2 株) 在小学生中的免疫效果。方法: 将431 名6～9 岁甲肝易感小学生随机分为两组。观察组接种甲肝减毒活疫苗(H2 株), 对照组接种乙肝基因工程疫苗。结果: 全部接种对象均未出现局部和全身不良反应;免疫后观察组抗-HAV 阳转率在T3 和T12时分别为85.44% 和85.64% ,而对照组则分别为12.93% 和28.32% 。结论: 两组的抗-HAV 阳转率差异有显著性, 表明国产甲肝减毒活疫苗 (H2 株) 具有良好的安全性和免疫原性     

冻干甲肝减毒活疫苗免疫原性及持久性分析

浙江省宁波市地处东南沿海,历史上是甲型肝炎(甲肝)高发区,常见甲肝周期性流行.2000年宁波市将甲肝疫苗接种纳入计划免疫管理,推广满2周岁儿童接种甲肝疫苗的免疫策略.新型冻干甲肝减毒活疫苗(H2株)是本地区推广接种的疫苗之一.该疫苗是在规范化液体甲肝疫苗(H2株)基础上研制的一种新剂型甲肝减毒活疫苗[1.2].它在稳定性、有效期及保证疫苗滴度方面比液体剂型有明显提高[3,4].为了进一步考核在甲肝流行区接种该疫苗的血清流行病学效果,验证现有免疫策略的合理性.2002～2006年在宁波市北仑区进行了冻干甲肝疫苗免疫原性及免疫持久性观察.结果报告如下.     

肾综合征出血热疫苗、甲肝疫苗联合接种的免疫效果

1998年吉林白城地区发生特大洪灾,历年来该地区有甲肝及肾综合征出血热散在流行,武警吉林某部官兵长年驻守此地,其中新兵有1380人。为确保大灾之后无疫情发生,我们对灾区部队新兵进行了肾综合征出血热(HFRS)灭活疫苗联合甲肝病毒(HAV)减毒活疫苗普种。既往有关HFRS灭活疫苗及HAV减毒活疫苗单独接种的安全性及免疫效果已有报道,而对HFRS灭活疫苗及HAV减毒活疫苗,同时接种的安全性及免疫效果研究未见报道,现将我们观察两种疫苗同时接种后的反应性和HFRS灭活疫苗及HAV减毒活疫苗的免疫效果报告如下。     

甲肝减毒活疫苗与麻疹减毒活疫苗联合免疫的实验研究

目的观察甲肝减毒活疫苗与麻疹减毒活疫苗联合免疫对甲肝疫苗免疫学效果的影响。方法对筛选出的甲肝易感者分两组,分别接种国内A、B两厂家甲肝疫苗,一部分接种者同时在对侧上臂接种了麻疹疫苗,一年时所有观察对象均又加强了一剂甲肝疫苗,于每次疫苗接种后24、48、72h观察局部及全身反应。一年半时检测接种对象血清标本中的抗-HAV。结果甲肝及麻疹疫苗接种后未见明显副反应。B厂家苗联合免疫组抗-HAV几何平均滴度(GMT)高于单纯甲肝疫苗接种组,A厂家苗组未见显著差异。结论甲肝疫苗与麻疹疫苗联合免疫安全性好,接种后不会降低甲肝疫苗免疫学效果。     

幼儿经两种剂型甲型肝炎疫苗免疫后抗-HAV阳转率观察

目前 ,在我国应用的甲型肝炎 (甲肝 )疫苗有甲肝减毒活疫苗和甲肝灭活疫苗 ,其主要接种对象是儿童。为了解幼儿园儿童甲肝自然感染水平 ,以及接种甲肝减毒活疫苗和甲肝灭活疫苗后的抗甲肝病毒抗体 (抗 -ＨＡＶ )阳转率。 1998年我们选择了 3所城镇幼儿园小班儿童进行观察 ,现将结果报告如下。1　观察对象的选择与分组　随机选择东莞市未接种过甲肝疫苗的 3所城镇幼儿园小班儿童 (3岁 )为观察对象 ,筛选出抗 -ＨＡＶＩｇＧ阴性者分为甲肝减毒活疫苗 1针组、甲肝灭活疫苗 3针组、甲肝灭活疫苗 2针组。2　疫苗及免疫程序　所用疫苗均购自市售批…     

Characterization of immune responses induced by inactivated,live attenuated and DNA vaccines against Japanese encephalitis virus in mice

Vaccination is the most effective countermeasure for protecting individuals from Japanese encephalitis virus (JEV) infection. There are two types of JEV vaccines currently used in China: the Vero cell-derived inactivated vaccine and the live attenuated vaccine. In this study, we characterized the immune response and protective efficacy induced in mice by the inactivated vaccine, live attenuated vaccine and the DNA vaccine candidate pCAG-JME, which expresses JEV prM-E proteins. We found that the live attenuated vaccine conferred 100% protection and resulted in the generation of high levels of specific anti-JEV antibodies and cytokines. The pCAG-JME vaccine induced protective immunity as well as the live attenuated vaccine. Unexpectedly, immunization with the inactivated vaccine only induced a limited immune response and partial protection, which may be due to the decreased activity of dendritic cells and the expansion of CD4+CD25+Foxp3+ regulatory T cells observed in these mice. Altogether, our results suggest that the live attenuated vaccine is more effective in providing protection against JEV infection than the inactivated vaccine and that pCAG-JME will be a potential JEV vaccine candidate.     

流行性乙型脑炎灭活疫苗与减毒活疫苗相结合的免疫策略研究

目的　为合理利用流行性乙型脑炎 (乙脑 )灭活疫苗和减毒活疫苗各自的优点 ,降低预防接种反应的发生率 ,提高免疫学效果 ,开展了乙脑灭活疫苗与减毒活疫苗相结合的免疫策略研究。方法　观察比较两种疫苗单一使用与联合使用的免疫学效果及安全性。结果　联合使用组在疫苗接种后 2 4h的全身中强以上发热反应发生率为 0 .73 % ,局部红晕反应为 1 .46 % ,而单一使用灭活疫苗组的发热反应发生率为 2 .8%。不同观察组疫苗接种后中和抗体几何平均滴度由免疫前的 1∶1 .0 5～1∶3 .35上升至 1∶47.34～ 1∶1 0 1 .30 ,联合使用组的中和抗体阳转率为 97.67% ,明显高于单一使用灭活疫苗组 86 .2 7%的阳转率 (χ2 =3 .89,P <0 .0 5) ,但与单一使用减毒活疫苗组 93 .75 %的阳转率差异无显著性 (χ2 =0 .74,P >0 .0 5)。结论　研究表明对婴幼儿使用乙脑灭活疫苗基础免疫、减毒活疫苗加强免疫有很好的免疫学效果及安全性 ,也是切实可行和比较理想的免疫策略     

Comparison of immunogenicity and safety of licensed Japanese encephalitis vaccines: A systematic review and network meta-analysis

IntroductionAnnually more than 100,000 Japanese encephalitis (JE) cases and 25,000 deaths worldwide are caused by JE virus infection. More than 15 JE vaccines are currently in use worldwide. It is unknown whether any of the vaccines is superior to the others in terms of immunogenicity and safety.MethodsFour databases were systematically searched for randomised controlled trials that compared two or more types of JE vaccines. Vaccines were classified into four classes: inactivated mouse brain-derived (oldest class), inactivated Vero cell, live chimeric, and live attenuated. Network meta-analysis was used to generate mixed effect estimates against inactivated mouse brain-derived vaccines for seroconversion, and against placebo for adverse event (AE) and severe adverse event (SAE).Results23 studies (38,496 participants) were included. All newer vaccine classes had better immunogenicity, the difference was statistically significant for inactivated Vero cell (OR = 2.98; 95 %CI: 1.02–8.65) and live chimeric (OR = 5.93; 95 %CI: 1.73–20.32) vaccines. Inactivated mouse-derived vaccines had the highest odds for AEs (OR = 2.27; 95 %CI: 1.59–3.23), the odds of AE of newer vaccines was not different to placebo. There was no difference in SAEs across vaccine classes.ConclusionsAll newer JE vaccines have comparable safety profiles, live chimeric and inactivated Vero cell vaccines are the most immunogenic among the newer vaccine classes.     

Development,Production, and Postmarketing Surveillance of Hepatitis A Vaccines in China

China has long experience using live attenuated and inactivated vaccines against hepatitis A virus (HAV) infection. We summarize this experience and provide recent data on adverse events after immunization (AEFIs) with hepatitis A vaccines in China. We reviewed the published literature (in Chinese and English) and the published Chinese regulatory documents on hepatitis A vaccine development, production, and postmarketing surveillance of AEFI. We described the safety, immunogenicity, and efficacy of hepatitis A vaccines and horizontal transmission of live HAV vaccine in China. In clinical trials, live HAV vaccine was associated with fever (0.4%–5% of vaccinees), rash (0%–1.1%), and elevated alanine aminotransferase (0.015%). Inactivated HAV vaccine was associated with fever (1%–8%), but no serious AEFIs were reported. Live HAV vaccine had seroconversion rates of 83% to 91%, while inactivated HAV vaccine had seroconversion rates of 95% to 100%. Community trials showed efficacy rates of 90% to 95% for live HAV and 95% to 100% for inactivated HAV vaccine. Postmarketing surveillance showed that HAV vaccination resulted in an AEFI incidence rate of 34 per million vaccinees, which accounted for 0.7% of adverse events reported to the China AEFI monitoring system. There was no difference in AEFI rates between live and inactivated HAV vaccines. Live and inactivated HAV vaccines manufactured in China were immunogenic, effective, and safe. Live HAV vaccine had substantial horizontal transmission due to vaccine virus shedding; thus, further monitoring of the safety of virus shedding is warranted.Key words: hepatitis A, vaccine, safety, efficacy     

Influenza vaccination with live-attenuated and inactivated virus-vaccines during an outbreak of disease.

Immunization procedures with live attenuated and inactivated vaccines were carried out on a group of young recruits at the beginning of an outbreak of infection due to an A/Victoria/3/75-related virus strain, which occurred in February 1977 in a military camp. A retrospective investigation on protection from clinical influenza was then performed in order to investigate whether immunization with live virus vaccines, administered at the beginning of an epidemic, could provide early protection from the disease. In the course of the two weeks following vaccination, laboratory-confirmed clinical influenza cases occurred in 4 subjects among the 110 volunteers of the control group which received placebo, and in 8, 7 and 4 subjects respectively of the 3 groups of about 125 individuals, each of which received one of the following vaccine preparations: (a), live attenuated A/Victoria/3/75 influenza virus oral vaccine, grown on chick embryo kidney culture; (b), live attenuated nasal vaccine, a recombinant of A/Puerto Rico/8/34 with A/Victoria/3/75 virus; and (c), inactivated A/Victoria/3/75 virus intramuscular vaccine. These data do not support the hypothesis that, during an epidemic of infection, early protection from clinical influenza can be achieved through immunization with live attenuated or inactivated influenza virus vaccines, in spite of the high immunizing capability of the vaccine preparations.     

Inactivated yellow fever 17D vaccine: Development and nonclinical safety,immunogenicity and protective activity

In the last 10 years new concerns have arisen about safety of the live, attenuated yellow fever (YF) 17D vaccine, in particular viscerotropic adverse events, which have a case-fatality rate of 64%. A non-replicating cell culture-based vaccine would not cause these adverse events, and potentially could be used in persons with precautions or contraindications to use of the live vaccine, including age <9 months and >60 years, egg allergy, immune suppression, and pregnancy. We developed a whole virion vaccine from the 17D strain inactivated with β-propiolactone, and adsorbed to aluminum hydroxide. The inactivated vaccine was highly immunogenic in mice, hamsters, and cynomolgus macaques. After a single dose in hamsters and macaques, neutralizing antibody titers were similar to those elicited by the live 17D vaccine (YF-VAX^®, Sanofi Pasteur). After two doses of inactivated vaccine, neutralizing antibody titers in hamsters were significantly higher than after a single dose of YF-VAX^® [geometric mean titer (GMT) 20,480 vs. 1940, respectively (P < 0.001, ANOVA)]. Hamsters given a single dose or two doses of inactivated vaccine or a single dose of YF-VAX^® were fully protected against hepatitis, viremia, weight loss and death after challenge with YF virus (Jimenez strain). A clinical trial of the inactivated vaccine (XRX-001) has been initiated.     

Bovine viral diarrhea virus types 1 and 2 antibody response in calves receiving modified live virus or inactivated vaccines

Serums from calves receiving eight different commercial vaccines containing modified live virus (MLV) or inactivated bovine viral diarrhea virus (BVDV) immunogens were assayed for antibodies to types 1 and 2 BVDV strains. The immune response to the types 1 and 2 BVDV strains were evaluated in 48 calves receiving one of the eight vaccines for each group. For 7/8 vaccines, the BVDV vaccine immunogen was only type 1 whereas the remaining vaccine contained both types 1 and 2 immunogens. Calves administered MLV vaccine received only one dose at day 0, whereas those calves receiving the inactivated vaccines were administered two doses initially at days 0 and 28. Selected calves were revaccinated with only one dose at day 140. Animals vaccinated with type 1 vaccines developed titers to a broad range of type 1 BVDV, both cytopathic (CP) and noncytopathic (NCP) biotypes, with lower titers evident to type 2 BVDV strains. For some animals, the BVDV serum antibodies did not persist. Revaccination at day 140 induced a significant four-fold increase in animals with intermediate to low antibody titers. There did not appear to be any clear differences in antibody responses between type 1 MLV or inactivated vaccines. The calves receiving the inactivated vaccine containing types 1 and 2 had similar antibody levels to both types.     

两种流行性乙型脑炎疫苗基础免疫的血清抗体观察

为考察流行性乙型脑炎 (乙脑 )减毒活疫苗和灭活疫苗的免疫效果和安全性 ,在新沂市和邳州市分别对 14 1名和 99名无乙脑疫苗接种史的 12～ 2 4月龄儿童 ,分别用乙脑减毒活疫苗和灭活疫苗进行基础免疫 ,在免疫前和免疫后 1个月采血用反向被动凝集抑制试验检测血清抗体。结果 :14 1名经减毒活疫苗免疫的儿童 ,抗体阳性率由免疫前的 2 2 70 %上升至免疫后的 87 2 3 % ,GMT由 1∶12 60上升为 1∶46 13 ;99名用灭活疫苗初免 2针的儿童 ,抗体阳性率由 13 13 %上升至 67 68% ,GMT由 1∶11 83上升至 1∶2 2 5 3。对免疫前抗体阴性的儿童 ,分别注射乙脑减毒活疫苗和灭活疫苗后 ,抗体阳转率分别为 83 49%和 62 79%。两种疫苗的安全性均好 ,接种后仅 17人 ( 0 0 7% )有轻度发热 ,11人 ( 0 0 4% )出现局部红肿。而减毒活疫苗出现反应的人数又少于灭活疫苗。本次观察表明 ,乙脑减毒活疫苗的免疫效果明显高于灭活疫苗 ,安全性好 ,接种次数少 ,适宜于推广使用。     

Comparison of live and inactivated influenza vaccine in high risk children

Bivalent, live attenuated intranasally administered influenza A vaccines were compared to inactivated, parenterally administered influenza A vaccines in a double-blind clinical trial in 55 children and young adults with cystic fibrosis. No qualitative or quantitative difference in symptomatology between the group receiving intranasal live vaccine versus placebo was observed. Serum immune responses to live vaccines were somewhat less than those to inactivated vaccine, particularly in adults. IgA response in nasal secretions was minimal in each vaccine group. In contrast, an IgG response in nasal secretions was commonly seen with both topically applied live vaccine and parenterally administered inactivated vaccine.