冻干Vero细胞狂犬病纯化疫苗在120例门诊病人中的临床效果

目的:观察国产冻干非洲绿猴肾传代细胞(Vero细胞)为基质制备的狂犬病纯化疫苗临床应用的免疫效果和安全性。方法:选择门诊部就诊的犬致伤者240例,分为试验组和对照组。试验组接种冻干Vero细胞狂犬病纯化疫苗,对照组接种地鼠肾狂犬病纯化疫苗。2组人群均按照狂犬病疫苗暴露后常规免疫程序进行接种,于全程接种后15d测定中和抗体,并观察不良反应。结果:试验组抗体阳性率为96.7%,明显高于对照组的90.0%,P<0.05;不良反应发生率为10.8%,明显低于对照组的21.7%,P<0.05。结论:Vero细胞纯化疫苗抗体阳转率高、不良反应发生率低,临床应用优于地鼠肾纯化疫苗,适宜推广使用。     

人用狂犬病疫苗的不良反应分析

目的探讨人用狂犬病疫苗接种后的不良反应发生情况。方法收集2009年~2015年接种的800例狂犬病疫苗的人员发生的120例不良反应人员,本组资料采用的狂犬疫苗有进口冻干人用狂犬病疫苗(Vero细胞)、国产冻干人用狂犬病疫苗(Vero细胞)、国产液体人用狂犬病疫苗(Vero细胞)三种。严格按照接种程序进行接种。对发生不良反应的人员进行总结和分析。结果 2009年~2015年接种的800例狂犬病疫苗的人员发生的120例不良反应人员,不良反应发生率为15.0%。其中局部反应50例,占6.25%,全身反应70例,占8.75%,根据疫苗种类的不同,进口冻干人用狂犬病疫苗接种500例,发生不良反应12例,不良反应发生率为10.9%,且均为局部反应,国产冻干人用狂犬病疫苗接种190例,发生不良反应28例,不良反应发生率为14.7%,且均为局部反应,国产液体人用狂犬病疫苗接种110例,发生不良反应80例,不良反应发生率为16.0%,其中局部不良反应10例,全身不良反应70例。结论人用狂犬病疫苗的不良反应率高,且国产冻干和进口冻干狂犬病疫苗以局部不良反应为主,国产冻干人用狂犬病疫苗与国产液体人用狂犬病疫苗不良反应发生率较差异不大,国产产液体人用狂犬病疫苗不良反应表现较重,出现全身反应例数不少。     

冻干人用狂犬病疫苗(MRC-5细胞)非临床安全性研究

目的 对冻干人用狂犬病疫苗(MRC-5细胞)进行全身主动过敏试验、肌肉刺激性、单次给药毒性和溶血性评价,以考察其安全性.方法 本研究起止时间为2014年3月至2016年10月.按照确定的工艺和质量标准,使用人二倍体细胞MRC-5培养狂犬病固定毒株,灭活、纯化后制备冻干人用狂犬病疫苗,质量检定合格后,用于开展全面的动物毒...     

2469例狂犬病疫苗接种者免疫效果分析

目的：了解人被犬、猫等宿主动物咬、抓伤，或破损皮肤被舔后，经全程接种狂犬病疫苗后的免疫效果；方法对2006年在区疾病预防控制中心门诊部（疾控门诊）就诊的对象，全程接种国产冻干纯化狂犬病疫苗（V1），与全程接种国产液体狂犬病纯化疫苗（V2），以及家住农村带回在社区卫生服务站全程接种，与在疾控门诊全程接种国产狂犬病疫苗，体内狂犬病毒抗体阳转情况进行统计分析；结果全程接种（V1）抗体阳转率（96．93％）高于全程接种（V2）抗体阳转率（90．48％，P〈0．01），家住农村疫苗带回，在村社区卫生服务站全程接种国产狂犬病疫苗阳转率（89．48％）低于在疾控门诊全程接种的阳转率（98．72％，P〈0．01）；结论（V1）免疫效果较（V2）好，接种狂犬病疫苗要统一保管、注意冷藏。     

15岁以下人群冻干人用狂犬病纯化疫苗效果观察

目的了解目前使用的冻干人用狂犬病纯化疫苗(Vero细胞)在15岁以下人群的免疫效果。方法依照我国卫生部《狂犬病暴露后处置工作规范(试行)》的要求全程免疫接种259例15岁以下狂犬病暴露者。完成全程接种后14d检测接种者血清中狂犬病抗体,并对检测结果进行统计分析。结果259例接种者中,狂犬病抗体检测阳性241例,抗体阳性率为93.05%;其中男孩189例,抗体阳性175例,阳性率92.59%;女孩70例,抗体阳性66例,阳性率94.29%。男女之间狂犬病抗体阳性率无显著性差异(χ2=0.04,P>0.05)。按年龄分组看:幼儿组(3岁以下)40例,学龄前儿童组(3～6岁)39例,学龄组(6～10岁)104例,少年组(10～15岁)76例,狂犬病抗体阳性人数分别为33、37、97、74例,阳性率分别为82.50%、94.87%、93.27%、97.37%,其中幼儿组与其他年龄组之间狂犬抗体阳性率有显著性差异(χ2=10.19,P<0.05)。结论冻干人用狂犬病纯化疫苗(Vero细胞)在15岁以下狂犬病暴露者中应用总免疫效果良好。     

人二倍体细胞狂犬病疫苗在健康成人中的安全性和免疫原性

在美国,对新开发的Lyssavac人二倍体细胞狂犬病疫苗(L-HDC)的安全性和免疫原性进行了临床试验。该疫苗为瑞士伯尔尼血清和疫苗研究所生产的冻干疫苗,不含抗生素和防腐剂,每剂0.5ml中至少含2.5IU灭活的狂犬病病毒抗原。美国3所兽医学院的296名健康学生完成了全程免疫,并提供了血样。所有受试者分暴露前接种和模拟暴露后接种两组,均为上臂三角肌接种。前者接     

费休氏容量法测量冻干人用狂犬病疫苗中水分含量的不确定度分析

目的对费休氏容量法测量冻干人用狂犬病疫苗中水分含量的不确定度进行分析,为评价该方法的准确性和可靠性提供科学依据。方法建立费休氏容量法测量冻干人用狂犬病疫苗中水分含量的数学模型,找出影响不确定度的因素,并对各个不确定度分量进行评估。结果计算出各变量的不确定度,取包含因子K=2,置信概率为95%,费休氏容量法测量冻干人用狂犬病疫苗中水分含量的扩展不确定度为0.082%。结论卡尔费休容量法检测冻干人用狂犬疫苗中水分含量时,不确定度主要由测定时卡尔费休试液的消耗体积和滴定度F值产生,该评价方法适用于冻干狂犬疫苗水分测定的不确定度评定与报告。     

液体狂犬病疫苗与冻干狂犬病疫苗的预防效果比较

狂犬病是由狂犬病病毒所致的、以侵犯中枢神经系统为主的人兽共患急性传染病。人类对狂犬病普遍易感,通常由病兽咬伤而感染,病死率达100%。狂犬病的主要预防措施为接种狂犬病免疫球蛋白和狂犬病疫苗。本文比较了液体与冻干两种剂型狂犬病疫苗的预防效果。     

狂犬病暴露者疫苗接种免疫临床效果研究分析

目的 对狂犬病疫苗的免疫效果进行深入的了解和仔细的分析.方法 通过对狂犬病暴露的160 例患者,进行狂犬病疫苗注射后所提供的临床资料进行回顾性的分析,通过采用狂犬病毒IgG作为抗体诊断试剂盒进行检测.结果 血清标本被检测的160 份中,仅有1 例死亡,有152 份患者抗体呈阳性,总阳性率达到95.6%;不同年龄组的阳性率为（P〈0.05）;不同的性别对血清抗体阳性率差异无显著性（P〉0.05）;不同疾病者疫苗接种后抗体检测情况有着不同的差异.结论 当前的狂犬病没有出现特效的治疗方式方法,加强对＂土狗＂以及流浪狗的管理工作,比如被狗抓伤或者咬伤,要及时进行就医,并且注射狂犬病疫苗,必要的时候,还要为患有狂犬患者注射免疫球蛋白.     

鹰潭市2004-2006年人用狂犬病疫苗接种效果分析

目的 了解2004-2006年间鹰潭市民被狗、猫、鼠等动物咬、抓伤后接种狂犬病疫苗的效果.   方法   对被动物咬、抓伤者全程接种狂犬病疫苗后15～20 d以ELlSA方法测定血清抗狂犬病抗体.   结果 在全程接种狂犬病疫苗的961名被动物咬、抓伤者中,抗体阳性893人,阳性率为92.9%.≥60岁组与＜60岁组间的抗体阳性率差异有统计学意义(X2=5.716,P＜O.01).   结论   被动物咬、抓伤者及时接种狂犬病疫苗是控制狂犬病的重要手段.     

干扰素在狂犬病疫苗中的佐剂效果研究

目的研究干扰素在狂犬病疫苗中的佐剂效果。方法将人用狂犬病疫苗与干扰素按一定比例混合,制成干扰素佐剂狂犬病疫苗。将干扰素佐剂狂犬病疫苗和无佐剂狂犬病疫苗分别免疫昆明小鼠,并于免疫前和免疫后4,7,14,30,60d时眶静脉采血,用快速免疫荧光灶抑制试验检测小鼠血清中和抗体;同时经腹腔免疫小鼠,第15天时取脾检测淋巴细胞转化率。结果干扰素佐剂狂犬病疫苗可促进免疫细胞增殖。与无佐剂狂犬病疫苗相比,干扰素佐剂狂犬病疫苗诱导产生中和抗体的时间早、滴度高。结论干扰素佐剂狂犬病疫苗具有良好的免疫学效果。     

冻干治疗用母牛分枝杆菌菌苗治疗慢性乙型肝炎疗效分析

目的：观察冻干治疗用母牛分枝杆菌菌苗（微卡）治疗慢性乙型肝炎（CHB）中的有效性和安全性。方法：CHB60例分成2组。治疗组：33例，主要用药为母牛分枝杆菌菌苗（微卡）＋乙肝疫苗＋双嘧达莫。对照组：27例，常规保肝治疗，主要用药为肌苷＋葡糖醛酸＋维生素C。6个月为1个疗程。结果：治疗组HBV-DNA、HBeAg阴转12例（36．36％），无不良反应。两组比较差异有显著性（P〈0．05）。结论：冻干治疗用母牛分枝杆菌菌苗治疗CHB安全有效，无不良反应。     

Drying-Induced Variations in Physico-Chemical Properties of Amorphous Pharmaceuticals and Their Impact on Stability II: Stability of a Vaccine

Objectives To investigate the impact of drying method on the storage stability of dried vaccine formulations. Materials and Methods A sucrose-based formulation of a live attenuated virus vaccine of a parainfluenza strain, with and without surfactant, was dried from by different methods; freeze drying, spray drying and foam drying. Dried powders were characterized by differential scanning calorimetry, specific surface area (SSA) analysis and by electron spectroscopy for chemical analysis (ESCA) to evaluate vaccine surface coverage in the dried formulations. Dried formulations were subjected to storage stability studies at 4, 25 and 37°C. The vaccine was assayed initially and at different time points to measure virus-cell infectivity, and the degradation rate constant of the vaccine in different dried preparations was determined. Results SSA was highest with the spray dried preparation without surfactant (∼ 2.8 m²/g) and lowest in the foam dried preparations (with or without surfactant) (∼ 0.1 m²/g). Vaccine surface coverage was estimated based on ESCA measurements of nitrogen content. It was predicted to be highest in the spray dried preparation without surfactant and lowest in the foam with surfactant. Stability studies conducted at 25°C and 37°C showed that the vaccine was most stable in the foam dried preparation with surfactant and least stable in spray dried preparations without surfactant and in all freeze dried preparations regardless of the presence of surfactant. Addition of surfactant did lower the SSA and vaccine surface coverage in freeze dried preparations but still did not improve storage stability. Conclusions In drying methods that did not involve a freezing step, good storage stability of Medi 534 vaccine in the dried form was found with low SSA and low vaccine surface accumulation, both of which integrate into low fraction of vaccine at the surface. Ice appears to be a major destabilizing influence.     

Immunogenicity and efficacy of Fermi-type nerve tissue rabies vaccine in mice and in humans undergoing post-exposure prophylaxis for rabies in Ethiopia

Rabies is an acute viral encephalitis that is invariably fatal following the manifestations of clinical signs. To subvert the course of the disease, rabies post-exposure prophylaxis (PEP) is widely utilized. The immunogenicity and efficacy of Fermi-type rabies vaccine produced in Ethiopia was determined in mice subjected to intracranial challenge with rabies virus, and in humans undergoing rabies PEP in Ethiopia. Mice were randomly assigned into 5 groups. Group 1 received 0.25 ml each of phenolized saline intraperitoneally for 14 consecutive days. Mice in groups 2-5 received 0.25 ml of rabies vaccine for human PEP for the same period of time. Blood samples were drawn from the retro-orbital vein of all mice on designated days for the determination of rabies virus neutralizing antibody (VNA) using the mouse serum neutralization test. Mice were subsequently challenged intracranially with rabies virus at a concentration of 64 MICLD50 90 days post initial vaccination. Rabies neutralizing antibody titers in the sera of immunized mice ranged from 4.6 to 25 IU/ml. Booster vaccine doses did not seem to induce significant increases in the immune response of vaccinated mice, all of whom withstood intracranial challenge with rabies virus. Rabies VNA was further determined in 12 patients vaccinated in accordance with the prescribed dosage of Fermi-type vaccine for human rabies PEP. Most had > 0.5 IU/ml of rabies VNA by day 14, and none detectable at day 1. In contrast to mice, booster doses of vaccine may contribute to slightly higher rabies VNA titers in humans but our small sample size, on top of significant defaulter rates in the study participants, limits our interpretation of the effects of booster vaccine doses. The results of this study are the first documentation of the efficacy and immunogenicity of the Ethiopian Fermi type nerve tissue vaccine in both humans and mice.     

Rabies antibody seroprotection rates among travelers in Nepal: "rabies seroprotection in travelers"

BACKGROUND: Rabies preexposure immunization is recommended for international travelers who are at risk for exposure to rabid animals, especially in areas where postexposure treatment may be limited. Rabies antibody seroprotection rates among international travelers has not been previously investigated. OBJECTIVE: To assess preexisting rabies seroprotection among travelers presenting to a health clinic in Nepal. METHODS: A prospective convenience sample of international travelers evaluated at a health center in Kathmandu, Nepal during a 2-month period. Subjects were eligible for inclusion if they had received rabies preexposure vaccination within the previous 5 years. Demographic information and vaccination records of rabies preexposure prophylaxis were obtained. Consenting subjects provided serum for rabies antibody measurement measured using the rapid fluorescent focus inhibition test. A dilution greater than or equal to 1:5 (0.5 IU/mL) was considered positive. Data were analyzed using chi-squares and two-sample t-tests with unequal variances. RESULTS: A total of 43 patients consented to enroll. Complete data were available for 38 patients. Subjects had received human diploid cell vaccine (HDCV) or purified Vero cell rabies vaccine (PVRV) vaccine, either via the intradermal or intramuscular route. All patients had adequate antibody titers except one, who had a titer below 0.5 IU/mL. There was no statistically significant relationship between antibody titer and type of vaccine, route of administration, time since vaccination, number of vaccinations, or patient age. CONCLUSIONS: Among 38 travelers to Nepal who had received documented preexposure rabies HDCV or PVRV vaccination series, 37 demonstrated adequate titers of > or =0.5 IU/mL and would be considered boostable if exposed to rabies virus. One traveler had a titer of <0.5 IU/mL. Type of vaccine, method of administration, number of vaccinations, and time since vaccination did not influence rabies antibody titer. Rabies vaccination with HDCV and PVRV vaccine was effective in stimulating adequate seroprotection in this sample of travelers.     

双抗夹心ELISA法快速检测人用狂犬病疫苗的效价

目的：用单克隆抗体制备的双抗夹心ELISA法，快速检测人用狂犬病疫苗中的狂犬病毒糖蛋白G的含量，并探讨其替代NIH法的可行性。方法：将疫苗样品用NIH法检定，同时以国家标准品为参考疫苗，用双抗夹心ELISA法检测。结果：用双抗夹心ELISA法测得的IgED50为2．60～2．78；用NIH法测得的IgED50为2．55～2．85。对两种检测方法进行F检验，两种检测方法的灵敏度有显著差异（F=5．76，P〈0．05）；用t检验法对这两种检测方法进行分析，表明两组测定值的差异无统计学意义（t=0．187，P〉0．05）。结论：双抗夹心ELISA法与NIH法测得的IgED50呈正相关性。与NIH法相比，双抗夹心ELISA法具有重复性好、成本低、快速等优点。用双抗夹心ELISA法取代NIH法测狂犬病疫苗效价是可行的。     

Immunogenicity study of abbreviated rabies preexposure vaccination schedules

OBJECTIVE: To evaluate abbreviated preexposure rabies vaccination schedules that would reduce cost and shorten time required for completion. METHOD: A random prospective immunogenicity study, using a group of 96 volunteer preclinical veterinary students, primary school children, and hospital-based health care workers. They were divided into six groups and administered abbreviated schedules of preexposure tissue culture rabies vaccines. Neutralizing antibodies were determined on days 0 and 360, and following boosters on days 367 and 374. RESULTS: All subjects, including one group that received only 0.1 mL intradermally at two sites on one day, had detectable neutralizing antibody titers 1 year later and responded with an accelerated antibody response when given booster injections. CONCLUSION: It might be possible to develop a 1-week and even one clinic visit preexposure vaccine schedule that would provide at least 1 year of immune memory.     

Investigation of the stabilizing effects of hydroxyethyl cellulose on LDH during freeze drying and freeze thawing cycles

Abstract

The objective of this study was to investigate both the cryoprotective and lyoprotective effects of the polymer hydroxyethyl cellulose (HEC) on the model protein lactate dehydrogenase (LDH) during freeze thawing and freeze drying cycles. The effect of annealing on both protein stability and the physical state of HEC was evaluated. HEC was used as a sole excipient in the protein formulations, and its stabilizing was compared to that of other excipients which are commonly used in freeze dried protein formulations. Furthermore, other quality aspects of the freeze dried samples containing solely HEC were investigated, such as, reconstitution time and product elegance. Protein stability was evaluated functionally by measuring the activity recovery of the model protein LDH. The physical state of HEC after freeze drying was investigated and compared to this of other studied solutes using differential scanning calorimetry and X-ray powder diffractometry. HEC showed superior cryoprotective effects on LDH during freeze thawing, and considerable lyoprotective effects during the freeze drying process. Annealing had limited influence on the stabilizing effect of HEC. The extensive reconstitution times of the HEC lyophilisates could be greatly improved by incorporation of the surfactant Tween 80 into the formulations prior to freeze drying.     

人用精制狂犬病疫苗不良反应与免疫学效果

目的 :观察人用精制狂犬病疫苗(PHKCRV)的免疫学效果及不良反应。方法 :选择332例健康者 ,按预防性免疫接种程序接种组 2 72人 ,其中PHKCRV 2 4 2人 ,用法国维尔博狂犬病疫苗 (PVCRV ) 30人。按应急性免疫接种程序接种PHKCRV的 6 0人中进行不同剂量 [全量 (1.0mL)组和半量 (0 .5mL)组 ,每组各 30人 ]接种。结果 :　PHKCRV不良反应率为 2 3% (7/ 30 )低于PVCRV的 33% (10 / 30 )。 2种疫苗中和抗体阳转率均为 10 0 %。中和抗体水平预防性接种组为 (10± 5)kU·L- 1,应急性接种组中全量组为 (9± 3)kU·L- 1;半量组为 (7.3± 2 .5)kU·L- 1。结论 :说明该疫苗不仅不良反应轻微而且免疫原性良好