流行性乙型脑炎减毒活疫苗人体接种反应免疫持久性观察研究

为了进一步了解流行性乙型脑炎减毒活疫苗的接种安全性，掌握其免疫效果及免疫持久性，本研究有代表性地抽取２岁以内婴幼儿３５９名，并将其分为两组，分别接种乙脑灭活疫苗和乙脑减毒活苗疫苗，经现场观察证实，两种疫苗接种后，仅极个别出现轻度接种反应，无严重反应发生，因而两种疫苗均是安全的，采用前瞻性方法研究其免疫学效果发现，基础免疫后，两种疫苗所产生的血清抗体达６０％左右，但仅能维持１年，第２年需加强免疫，抗     

甲型肝炎：甲型肝炎灭活疫苗与减毒活疫苗的免疫效果观察

目的：观察甲型肝炎灭活疫苗（灭活疫苗）和甲型肝炎减毒活疫苗（减毒活疫苗）基础免疫、加强免疫的效果。方法：2004年对湛江市赤坎区寸金管区156名2．10岁儿童进行调查．检测抗-HAV水平。结果：减毒活疫苗基础免疫后1个月抗-HAV阳性率为76．47％，灭活疫苗基础免疫后1个月抗-HAV阳性率为100％。     

甲型肝炎

两种国产甲肝减毒活疫苗的免疫效果及副作用观察——李艳群（福建泉州市卫生防疫站362000）；《中华中西医临床杂志》，2005，5（5）：439-440【目的：为比较冻干型的国产甲肝减毒活疫苗和水剂型甲肝减毒活疫苗的免疫效果及临床副反应。方法：选择2002年11月到2003年3月，在泉州市卫生防疫站预防接种门诊接种人群，分组接种冻干型甲肝减毒活疫苗和水剂型甲肝减毒活疫苗，观察接种后局部反应及全身反应情况。在接种后1个月，采用酶标免疫法（ELISA）进行甲肝抗体检测。结果：检测出接种冻干型甲肝疫苗和水剂型疫苗人群的阳性率分别为95．2％和84％．副作用反应率分别为2．7％和7．6％。     

两种国产甲肝减毒活疫苗的免疫效果及副作用观察

（福建泉州市卫生防疫站362000）；《中华中西医临床杂志》，2005，5（5）：439-440【目的：为比较冻干型的国产甲肝减毒活疫苗和水剂型甲肝减毒活疫苗的免疫效果及临床副反应。方法：选择2002年l1月到2003年3月，在泉州市卫生防疫站预防接种门诊接种人群，分组接种冻干型甲肝减毒活疫苗和水剂型甲肝减毒活疫苗，观察接种后局部反应及全身反应情况。在接种后1个月，采用酶标免疫法（ELISA）进行甲肝抗体检测。结果：检测出接种冻干型甲肝疫苗和水剂型疫苗人群的阳性率分别为95．2％和84％，副作用反应率分别为2．7％和7．6％。结论：冻干型甲肝减毒活疫苗的免疫效果优于水剂型，临床副反应较小，是现阶段预防甲型肝炎较为理想的疫苗，可代替水型疫苗进行推广。     

婴儿麻疹风疹减毒活疫苗联合免疫血清流行病学研究

目的为探讨麻疹、风疹减毒活疫苗联合免疫的可行性。方法于1997年4～12月随机选择了342名8月龄婴儿进行研究,所有入选婴儿被随机分成3组,第1组105人,皮下接种BRD-Ⅱ株风疹疫苗;第2组105人,分别在左右臂同时皮下接种风疹疫苗和麻疹疫苗;第3组132人,皮下接种沪191株冻干麻疹疫苗。结果在免疫前,第1组与第2组的风疹血凝抑制(HI)抗体阳性率均为2.86％,几何平均滴度(GMI)均为1:1.06,第2组与第3组麻疹HI抗体阳性率分别为2.86％和5.30％,GMT为1:1.02和1:1.60。免疫后1个月,第1组与第2组的风疹HI抗体阳性率分别为98.10％和99.05％,GMT分别为1:144.15和1:148.99。两者的差异无显著的统计学意义。第2组与3组的麻疹HI抗体阳性率分别为99.05％和97.73％,GMT分别为1:35.10和1:32.85,两者的差异亦无显著的统计学意义。所有免疫的儿童均未发现局部和全身反应。结论研究结果表明:风疹、麻疹减毒活疫苗联合免疫可产生与常规免疫相同的免疫应答,风疹疫苗初免月龄定于8月龄与麻疹疫苗联合免疫是可行的。     

浙江省肾综合征出血热(HFRS)-Ⅰ型鼠脑纯化疫苗安全性、血清学、防病效果和免疫策略研究

目的　现场观察、考核兰州生物制品研究所生产的HFRS -Ⅰ型鼠脑纯化疫苗的安全性、血清免疫学与防病效果 ,并确定其免疫程序和免疫策略。方法　试验组和对照组按随机整群分组法进行分组 ;采用 0、7、2 8d及免后 1年加强 1针的免疫程序 ;分别采集免前、全程接种后 2周、加强前、加强后两周、加强后 1、2、3、4、5年的部分接种者全血和微量耳垂血 ,分别测定其中和抗体和IFA抗体 ,观察疫苗的血清免疫学效果和现场流行病学防病效果。结果　在 1995年 8月～ 2 0 0 1年 12月的 6年时间里从疫苗开始接种到加强后 5年 ,观察了HFRS -Ⅰ型鼠脑灭活纯化疫苗的安全性、血清免疫学效果和流行病学防病效果等。纵观结果 :证明该疫苗除了因疫苗中残留蔗糖导致较重较普遍的局部反应外 ,未发现其他严重的副反应 ,证明疫苗有较好安全性。从血清免疫效果看 ,86例全程接种后两周的免疫者血清 ,IFA抗体阳转率达 10 0 % ,中和抗体阳转率为4 4 4 4 % (8/ 18)。 1年后 ,IFA抗体和中和抗体阳性率分别下降到 2 8 5 7%和 14 80 %。但加强后 2周的血清IFA抗体和中和抗体阳性率分别反弹至 83 33%和 5 5 5 6 % ,其抗体几何平均滴度也随之回升 ,但不十分明显。此外 ,在加强后 2年IFA和中和抗体阳性率再次下降到较低水平 ,分别为     

800例乙脑疫苗接种儿童不良反应观察及其护理体会

目的 观察800例乙脑疫苗接种儿童的不良反应并总结其护理体会。方法 选取2013年1月—2014年1月在我中心接受乙脑疫苗首次接种的儿童800例,均于上臂外侧三角肌下缘附着处皮下接种乙脑减毒活疫苗,密切观察接种儿童不良反应并总结其护理方法和处理原则。结果 800例儿童接种乙脑疫苗出现局部红肿375例(46.9%)、发热362例(42.3%)、过敏反应43例(5.4%)、其他19例(2.4%)。结论 儿童接种乙脑疫苗的不良反应较多,以局部红肿及发热为主,在科学控制及预防的同时给予心理护理及不良反应护理对接种儿童具有重要意义。     

一例接种乙脑疫苗后意外死亡的调查报告

目的分析一例因接种乙脑疫苗后意外死亡的原因,提高预防接种门诊工作人员的风险意识,减少异常反应尤其是死亡的发生,消除预防接种后意外死亡给免疫规划工作带来的不良影响。方法对预防接种后的死亡病例进行现场调查和尸检,并对接种的同批号疫苗进行检测,综合分析死亡原因。结果受种者出生及生长发育均无异常,所接种的乙脑减毒活疫苗运输、存储和接种操作规范,同批次疫苗检测结果符合规定。结论受种者排除因疫苗质量和接种操作不当而引起意外死亡,无直接证据证明受种者死亡与接种乙脑减毒疫苗相关,属于偶合症。     

2002-2006年开江县健康儿童流行性乙型脑炎血清抗体监测

目的了解开江县健康儿童乙脑抗体阳性率动态变化情况，为乙脑防制提供科学依据。方法2002—2006年每年5月在乙脑流行地区采集1～9岁健康儿童静脉血2ml并分离血清，进行乙脑抗体IgG检测，2002—2003年采用反向被动血凝抑制试验（RPHI），2004—2006年采用酶联免疫吸附试验（ELISA）。2006年调查全县接种乙脑疫苗情况。结果2002—2006年取健康儿童血清455份，乙脑抗体阳性270份，阳性率为59．34％，2002—2006年抗体阳性率依次为48．33％、54．35％、62．00％、63．08％及63．77％，各年度差异无统计学意义（X2=5．75，P〉0．05）。男女抗体阳性率各为56．65％和63．02％，两者差异无统计学意义（X^2=1．86，P〉0．05）。各年龄组抗体阳性率以2岁组最低（32．35％），8岁最高（82．76％），各年龄组之间差异有统计学意义（X^2=25．17，P〈0．05）。2002—2006年全县接种乙脑疫苗75496人，平均每年在15000人以上。调查1～7岁儿童169名，有乙脑疫苗接种的79名，接种率为46．75％，1～4岁接种率42．15％，低于5～7岁的58．33％，两者差异无统计学意义（X^2=3．62，P〉0．05）。结论加强低年龄组，特别是0～4岁儿童乙脑疫苗的预防接种，能有效地控制乙脑的发生和流行。     

甲型肝炎

Pichia pastoris酵母中表达人源中和性抗甲型肝炎病毒scFv-Fc融合抗体的研究；学龄前儿童甲型肝炎疫苗免疫效益评价；H2株甲肝减毒活疫苗安全性及免疫效果观察；甲型肝炎灭活疫苗抗原剂量的优化.     

Prevention of symptomatic seasonal influenza in 2005-2006 by inactivated and live attenuated vaccines

BACKGROUND: The efficacy of influenza vaccines may vary annually. In 2004-2005, when antigenically drifted viruses were circulating, a randomized, placebo-controlled trial involving healthy adults showed that inactivated vaccine appeared to be efficacious, whereas live attenuated vaccine appeared to be less so. METHODS: In 2005-2006, we continued our trial, examining the absolute and relative efficacies of the live attenuated and inactivated vaccines in preventing laboratory-confirmed symptomatic influenza. RESULTS: A total of 2058 persons were vaccinated in October and November 2005. Studywide influenza activity was prolonged but of low intensity; type A (H3N2) virus was circulating, which was antigenically similar to the vaccine strain. The absolute efficacy of the inactivated vaccine was 16% (95% confidence interval [CI], -171% to 70%) for the virus identification end point (virus isolation in cell culture or identification through polymerase chain reaction) and 54% (95% CI, 4%-77%) for the primary end point (virus isolation or increase in serum antibody titer). The absolute efficacies of the live attenuated vaccine for these end points were 8% (95% CI, -194% to 67%) and 43% (95% CI, -15% to 71%), respectively. CONCLUSIONS: With serologic end points included, efficacy was demonstrated for the inactivated vaccine in a year with low influenza attack rates. The efficacy of the live attenuated vaccine was slightly less than that of the inactivated vaccine, but not statistically greater than that of the placebo.     

Safety and immunogenicity of a fully liquid vaccine containing five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus influenzae type b conjugate vaccines administered at two, four, six and 18 months of age

OBJECTIVE: The safety, immunogenicity and lot consistency of a fully liquid, five-component acellular pertussis combination vaccine, comprised of diphteria, tetanus and acellular pertussis, inactivated polio vaccine, Haemophilus influenzae type b (DTaP-IPV-Hib [Pediacel, sanofi pasteur, Canada]) were assessed and compared with that of Hib vaccine reconstituted with the five-component acellular pertussis combination vaccine (DTaP-IPV//Hib, Pentacel [sanofi pasteur, Canada]). METHODS: Infants were recruited at vaccine study centres in Montreal, Quebec; Simon Fraser Health Region, British Columbia, and southern Alberta after the protocol had been approved by the relevant institutional ethics committees. Written informed consent was obtained from the parents or guardians of all subjects. At two months of age, the infants were randomly assigned to receive one of three consecutive production lots of DTaP-IPV-Hib by intramuscular injection. Reactions to vaccinations were assessed by parental observation and through telephone interviews conducted by study nurses. Blood samples were obtained at two, six, seven, 18 and 19 months of age for measurement of antibodies to vaccine antigens. RESULTS: Most injection site and systemic reactions were mild or moderate, and of brief duration. All infants were protected against tetanus, diphtheria and all three polio serotypes after both primary and booster vaccinations. Antibody responses to pertussis antigens were similar to those observed in Swedish infants, in whom the five-component vaccine was shown to be 85% effective. Proportions of infants with antipolyribosylribitol phosphate antibody of 0.15 mug/mL or greater and 1.0 mug/mL or greater, were 97.9% and 88.9%, respectively, following primary immunization, and 100% and 99% following booster vaccination. Safety and immunogenicity results with both reconstituted and fully liquid combination vaccines were comparable. CONCLUSIONS: The fully liquid combination vaccine was comparable in terms of safety and immunogenicity with the reconstituted combination vaccine.     

Persistence in humans of antibody after immunization with four alphavirus vaccines.

Immunization with attenuated VEE virus vaccine resulted in persistence of neutralizing antibody for 12 years. Immunization with inactivated WEE vaccine converted 83% of the subjects, killed EEE vaccine converted 27% and killed Chikungunya vaccine induced no significant titers. Antibody formed as a result of immunization with inactivated vaccines was of short duration, i.e. less than 1 year. Attenuated VEE was responsible for some heterologous antibody rises to the other three alphaviruses. Among the inactivated vaccines WEE and Chikungunya vaccines produced one heterologous rise each to EEE virus.     

狂犬病病毒糖/核蛋白基因疫苗和IL-18在犬的免疫试验研究

目的　检测狂犬病病毒糖 /核蛋白“二价”基因疫苗及IL - 18在犬体内的免疫效果 ,并确定不同包裹剂对基因疫苗免疫效果的影响。方法　本试验以 pIRES1neo和人用灭活苗分别作为阴、阳性对照 ,以糖 /核蛋白双基因共表达载体 pIGN单独或与IL - 18的真核表达载体pIIL18混合 ,以司苯 -甘油混合或以生理盐水溶液形式 ,按每条犬 2 0 0 μgDNA/ml,接种 3次 (其中 1组第 3次加强免疫时采用浓缩的狂犬病灭活苗 ) ,间隔 2周的免疫程序 ,经股四头肌进行注射免疫。通过间接ELISA、细胞中和试验及淋巴细胞转化试验分别检测体液和细胞免疫水平。结果与结论　结果显示 ,1.所有试验组在第 3次加强免疫后特异性抗体和中和抗体水平显著高于阴性对照组 ;pIGN pIIL18组诱导的细胞免疫水平高于无 pIIL18的 pIGN免疫组 ;2 .以司苯 -甘油作为包裹剂的基因疫苗诱导产生的免疫应答水平与裸质粒 (生理盐水溶液 )形式的基因疫苗间无显著差异 ;3.以糖 /核蛋白二价基因疫苗pIGN作为基础免疫 ,再以狂犬病浓缩灭活苗加强免疫后 ,能迅速诱导较高的体液免疫应答水平。以上结果说明 ,狂犬病病毒糖 /核蛋白“二价”DNA疫苗具有实际应用于免疫预防的潜力。     

Immunity to influenza A virus infection in young children: a comparison of natural infection, live cold-adapted vaccine, and inactivated vaccine

Live attenuated, cold-adapted (ca) influenza A vaccines administered intranasally have been well characterized as safe and immunogenic, but comparative data on protective efficacy are required for further development. In this study, 59 young children were divided into the following four groups based on prior exposure to influenza A (H3N2) virus: natural infection, live ca vaccine given intranasally, inactivated vaccine given im, and no previous exposure. Virus challenge with homologous live ca vaccine occurred 12 months after vaccination or natural infection. Prior natural infection and live ca vaccine significantly reduced ca virus shedding after challenge compared with inactivated vaccine or no prior exposure to influenza A virus. Prechallenge nasal IgA, detected almost exclusively in subjects naturally infected or vaccinated with live ca virus, was associated with protection. Although inactivated vaccine failed to produce significant local IgA during the primary response, it seemed to prime for secondary local antibody responses after challenge with live ca virus.     

Antibody responses against influenza A(H1N1)pdm09 virus after sequential vaccination with pandemic and seasonal influenza vaccines in Finnish healthcare professionals

Background Influenza A(H1N1)pdm09 virus has been circulating in human population for three epidemic seasons. During this time, monovalent pandemic and trivalent seasonal influenza vaccination against this virus have been offered to Finnish healthcare professionals. It is, however, unclear how well vaccine‐induced antibodies recognize different strains of influenza A(H1N1)pdm09 circulating in the population and whether the booster vaccination with seasonal influenza vaccine would broaden the antibody cross‐reactivity. Objectives Influenza vaccine‐induced humoral immunity against several isolates of influenza A(H1N1)pdm09 virus was analyzed in healthcare professionals. Age‐dependent responses were also analyzed. Methods Influenza viruses were selected to represent viruses that circulated in Finland during two consecutive influenza epidemic seasons 2009–2010 and 2010–2011. Serum samples from vaccinated volunteers, age 20–64 years, were collected before and after vaccination with AS03‐adjuvanted pandemic and non‐adjuvanted trivalent seasonal influenza vaccine that was given 1 year later. Results Single dose of pandemic vaccine induced a good albeit variable antibody response. On day 21 after vaccination, depending on the virus strain, 14–75% of vaccinated had reached antibody titers (≥1:40) considered seroprotective. The booster vaccination 1 year later with a seasonal vaccine elevated the seroprotection rate to 57–98%. After primary immunization, younger individuals (20–48 years) had significantly higher antibody titers against all tested viruses than older persons (49–64 years) but this difference disappeared after the seasonal booster vaccination. Conclusions Even a few amino acid changes in influenza A HA may compromise the vaccine‐induced antibody recognition. Older adults (49 years and older) may benefit more from repeated influenza vaccinations.     

Secretory and serum immunoglobulin class-specific antibodies to poliovirus after vaccination

Immune responses in serum and saliva were studied in Pakistani children by enzyme-linked immunosorbent assay after natural exposure to poliovirus and vaccination with live or inactivated poliovirus vaccines. Swedish children unexposed to wild poliovirus who had almost 100% vaccination coverage with inactivated vaccine at 8, 9, and 18 months and at 5 years of age were analyzed for comparison. Natural exposure induced secretory IgA (SIgA) antibodies to poliovirus in the saliva of Pakistani infants at one month of age that reached adult levels at six months. No difference in levels of salivary antibody at eight months was observed between groups vaccinated with either live or inactivated vaccines. Vaccination with live or inactivated vaccine starting at 2 or 3 months of age resulted in high titers of IgG antibody to poliovirus in serum, the highest of which occurred after four doses of live vaccine. In Sweden, an increase of antibody in serum was observed after the third vaccination. IgA antibodies continued to increase subsequently, whereas IgG antibodies reached a plateau. The SIgA response in saliva initially appeared on the third vaccination, with a significant increase after the fourth. Repeated vaccination with inactivated poliovirus vaccine induces specific SIgA antibodies. Adults all had SIgA antibodies to poliovirus in saliva.     

Short report: absence of protective neutralizng antibodies to West Nile virus in subjects following vaccination with Japanese encephalitis or dengue vaccines

Protection of individuals against West Nile (WN) encephalitis is an emerging concern in the United States and Europe. We investigated whether immunization with licensed inactivated Japanese encephalitis (JE) vaccine or experimental live attenuated dengue vaccines resulted in induction of cross-neutralizing antibodies against WN virus. Protective neutralizing antibody titers to WN virus were not detected in any volunteer despite successful immunization to related flaviviruses. Vaccination against JE or dengue is unlikely to prevent WN virus infection but may still protect against disease.     

Nanoparticles in influenza subunit vaccine development: Immunogenicity enhancement

The threat of novel influenza infections has sparked research efforts to develop subunit vaccines that can induce a more broadly protective immunity by targeting selected regions of the virus. In general, subunit vaccines are safer but may be less immunogenic than whole cell inactivated or live attenuated vaccines. Hence, novel adjuvants that boost immunogenicity are increasingly needed as we move toward the era of modern vaccines. In addition, targeting, delivery, and display of the selected antigens on the surface of professional antigen‐presenting cells are also important in vaccine design and development. The use of nanosized particles can be one of the strategies to enhance immunogenicity as they can be efficiently recognized by antigen‐presenting cells. They can act as both immunopotentiators and delivery system for the selected antigens. This review will discuss on the applications, advantages, limitations, and types of nanoparticles (NPs) used in the preparation of influenza subunit vaccine candidates to enhance humoral and cellular immune responses.     

Vaccines in Development against West Nile Virus

West Nile encephalitis emerged in 1999 in the United States, then rapidly spread through the North American continent causing severe disease in human and horses. Since then, outbreaks appeared in Europe, and in 2012, the United States experienced a new severe outbreak reporting a total of 5,387 cases of West Nile virus (WNV) disease in humans, including 243 deaths. So far, no human vaccine is available to control new WNV outbreaks and to avoid worldwide spreading. In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine. MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines. We previously described a vector derived from the Schwarz MV vaccine strain that stably expresses antigens from emerging arboviruses, such as dengue, West Nile or chikungunya viruses, and is strongly immunogenic in animal models, even in the presence of MV pre-existing immunity. A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.