炭疽疫苗与钩体疫苗联合免疫效果分析

目的 评价炭疽疫苗和钩体疫苗进行联合免疫的有效性,为人群联合接种提供理论依据.方法 96只昆明鼠按分层随机分组的方法分为6组,每组16只,雌雄各半.将单独接种确定的每种疫苗的最佳免疫剂量(炭疽疫苗1/10、钩体疫苗1/5的人用剂量)进行联合接种,同时组合两种疫苗最佳剂量的临近剂量组(炭疽疫苗1/20、1/40,钩体疫苗1/3的人用剂量)进行联合接种,采用ELISA方法检测炭疽特异性抗体,MAT法检测钩体各型特异性抗体.结果 疫苗接种后,小鼠能够对各剂量产生免疫反应,抗- PA IgG抗体的最高平均抗体滴度为1:504,抗芽孢IgG抗体的最高平均抗体滴度为1∶513.炭疽疫苗各个剂量组间抗体水平存在统计学差异(P＜0.05);流感伤寒型抗体的最高平均抗体滴度为1∶231,秋季型抗体的最高平均抗体滴度为1∶610,钩体疫苗各型抗体各个剂量组间无统计学差异(P＞0.05).结论 炭疽疫苗与钩体疫苗联合接种以炭疽疫苗人用剂量的1/10和钩体疫苗的人用剂量的1/5配伍最佳.     

炭疽疫苗和钩端螺旋体疫苗联合接种安全性实验研究

目的 对炭疽疫苗和钩端螺旋体(简称钩体)疫苗进行联合接种动物实验研究,评价联合接种疫苗的安全性,确定最佳实验免疫剂量,为炭疽疫苗和钩体疫苗的人群联合接种提供理论依据.方法 96只实验鼠分层随机分为6组,每组16只,雌雄各半.采用背部皮下接种,取炭疽疫苗1/10、钩体疫苗1/5的人用剂量进行联合接种,同时组合两种疫苗的临近剂量组,即炭疽疫苗1/20、1/40,钩体疫苗1/3的人用剂量进行联合接种,运用体重、血液学指标以及病理组织学等指标对疫苗的安全性进行评价.结果 实验动物接种2种疫苗48～72 h后,部分动物接种部位出现局部水肿,2组(Ⅰ、Ⅲ组)出现动物死亡.免疫后某些时间点白细胞计数有变化,其他指标与对照组差异无统计学意义(均有P＞0.05).结论 采用炭疽疫苗和钩体疫苗最佳剂量进行联合接种是可行的.     

肾综合征出血热滴鼻疫苗壳聚糖载体的筛选

摘要:目的 筛选肾综合征出血热滴鼻疫苗壳聚糖载体,为进一步研究其滴鼻或气雾疫苗提供依据。方法 48只昆明鼠按完全随机分组的方法分为4组,每组12只,采用3种不同粘度的壳聚糖作为载体,制成终浓度为0.1%壳聚糖的病毒液进行鼻腔接种,采用ELISA方法检测肾综合征出血热特异性IgG抗体。结果 疫苗接种后,小鼠能够对各剂量组产生免疫反应,Ⅱ、Ⅲ组能诱导较高、较快血清抗体滴度的增加,免疫后3周,血清抗体滴度维持在较高的水平,但各个实验组间无统计学差异(P>0.05)。结论 本实验得出壳聚糖能够增强疫苗的抗体反应,Ⅱ、Ⅲ组效果更佳。     

不同剂量甲型肝炎减毒活疫苗免疫原性与免疫持久性观察

目的：观察不同剂量的甲型肝炎（甲肝）减毒活疫苗免疫原性与免疫持久性。方法：对河北省正定县4个村166名6－8岁事先经血清检测抗－HAV阴性的易感儿童,按村分成4组,分别给予0.5、1、2及2剂经60℃3h灭活处理的甲肝减毒活疫苗（滴度为10^6.52TCID50）。并于接种后3、12、24、36及48个月采集观察对象血清,采用Abbott-IMx mEIA试剂检测血清抗－HAV。并对接种1剂、2剂活疫苗组免后4年部分血清检测中和抗体。结果：免后3个月抗体阳转率、抗体几何平均滴度（GMT）同疫苗滴度呈剂量效应关系。免疫各组抗体水平于免疫后3个月达高峰后逐年下降,12个月内下降较明显,12个月后下降缓慢。免疫后4年接种2剂活疫苗组抗体阳性率与GMT均高于接种0.5剂及1剂组。接种1、2剂活疫苗组部分经Abbott-IMx mEIA试剂检测抗－HAV阴性的血清检测中和抗体,其阳性率为60％及83％。结论：甲型肝炎减毒活疫苗的免疫原性与免疫持久性同疫苗的滴度有关,滴度为10^6.83TCID50的减毒活凤苗具有较理想的免疫原性及免疫持久性。减毒活疫苗接种后近期内不必予以加强免疫。     

两种重组乙型肝炎疫苗免疫效果比较

目的 比较两种重组乙型肝炎(乙肝)疫苗的免疫效果。方法 对1304名18～50岁年龄组人群的血清样品用放射免疫试验(RIA)检测HBsAg、抗-HBs、抗-HBc，该3项指标均为阴性者注射重组乙肝疫苗。在注射疫苗后1年和3年时检测血清抗-HBs滴度，以观察不同年龄、不同性别的成人接种重组乙肝疫苗的免疫效果。结果 成人接种重组乙肝疫苗后均能获得良好的免疫效果，接种5μg重组(酵母)乙肝疫苗1年和3年后，抗-HBs阳性率分别为82．76％、70．77％，抗体滴度分别为55．91mIU／ml、35．41mIU／ml；接种10μg重组(CHO)疫苗1年和3年后，抗-HBs阳性率分别为83．74％、72．22％，抗体滴度分别为56．89mIU/ml、30．29mIU／ml.5μg重组(酵母)和10μg重组(CHO)乙肝疫苗免疫效果基本相同。两种疫苗抗-HBs阳性率和滴度随着免疫时间的延长而降低。结论 18～50岁年龄组人群接种重组(酵母)和重组(CHO)乙肝疫苗均可获得良好的免疫效果。     

新生儿基础免疫接种不同剂型乙型肝炎疫苗不同时间免疫水平比较

目的探讨新生儿分别接种10μg与5μg乙型肝炎(乙肝)疫苗免疫后不同时间免疫水平,为调整新生儿乙肝疫苗免疫程序提供科学依据。方法采用病例对照研究方法观察新生儿接种不同剂量乙肝疫苗后不同时间段人群抗体水平变化,采用化学放光法检测血清抗体水平。结果两队列新生儿在全程接种乙肝疫苗后1个月、6个月、12个月,低无应答率接种10μg组均低于接种5μg乙肝疫苗组,乙肝表面抗体滴度接种10μg组均高于接种5μg乙肝疫苗组,免疫后12个月内两组乙肝表面抗体滴度均呈下降趋势,免疫后12个月10μg乙肝疫苗组的乙肝表面抗体阳性率高于接种5μg乙肝疫苗组。结论新生儿接种10μg乙肝疫苗的免疫效果优于5μg乙肝疫苗。     

乙肝疫苗低(无)应答儿童再免疫效果观察

目的评价乙肝疫苗低应答/无应答儿童重新接种或加大剂量接种后的免疫效果。方法用酶联免疫法（ELISA）筛选出1岁以内已全程接种乙肝疫苗的4-6岁儿童血清HBsAg、抗-HBs、抗-HBc 3项指标全为阴性者,再用固相放射免疫法（RIA）复核并对抗-HBs小于10mIU/ml者,使用重组（CHO细胞）乙肝疫苗,按10μg剂量/1针次和20μg剂量/1针次分2组接种,均为0、1、6程序接种3针,完成接种后1-2月时采血,检测抗-HBs水平。结果2019例筛选儿童血清HBsAg、抗-HBs、抗-HBc 3项指标全为阴性者672例,占33.28%。抗-HBs〈2.1mIU/ml的无应答儿童占27.44%,2.1-9.9mIU/ml的低应答儿童占5.05%。10μg剂量接种组采集到158例血清,抗-HBs≥10mIU/ml者155例,占98.10%,GMT为364.36mIU/ml。20μg剂量接种组采集到173例血清,抗-HBs≥10mIU/ml者172例,占99.42%,GMT为392.86mIU/ml。2组疫苗再免疫后抗-HBs的GMT增幅为53.61-721.87倍。结论乙肝疫苗无（低）应答儿童重新接种乙肝疫苗3针后免疫效果良好,10μg剂量组与20μg剂量组的抗体达到保护水平率差异无统计学意义,无应答儿童再免疫后产生的抗体GMT水平2组差异无统计学意义,低应答儿童的抗体GMT水平则表现为20μg剂量组高于10μg剂量组。     

精制甲型肝炎灭活疫苗(Vero细胞)维罗信TM的安全性和免疫原性随机对照研究

目的评价精制甲型肝炎灭活疫苗(Vero细胞)的安全性和免疫原性。方法2005年1～8月在广西恭城县选择1507名健康人群,以随机、双盲、平行对照方法,观察该疫苗的不良反应,抗体阳转率和抗体水平(GMT),应用EIA竞争抑制法检测血清抗甲型肝炎抗体(抗-HAVIgG)。结果成人剂量组试验疫苗全身、局部反应发生率分别为8.80%、2.67%,与对照疫苗(分别为12.41%、4.41%)相比,无显著差异;儿童剂量组试验疫苗全身、局部反应发生率分别为10.60%、2.28%,与对照疫苗(10.71%、2.86%)相比,亦无显著性差异。维罗信首针免疫后1个月,儿童剂量组和成人剂量组的阳转率分别为88.2%、93.8%,两针全程免疫1个月后两组抗体阳转率均达到100%,抗体滴度分别为16447、8555mIU/ml,对照疫苗分别为1946、5881mIU/ml,儿童剂量组抗体滴度与对照组相比有显著性差异。结论精制甲型肝炎灭活疫苗(Vero细胞)在儿童和成人中应用具有良好的安全性,采用0,6个月免疫程序免疫后抗体阳转率达100%,并有高的抗体滴度。     

甲型肝炎灭活疫苗（Vero细胞）人体接种的安全性和免疫原性研究

目的 研究在中国儿童和成人中接种江苏延申生物科技股份有限公司研制的甲型肝炎灭活疫苗(Vero细胞)的安全性和免疫原性.方法 在广西蒙山县筛选甲型肝炎病毒易感者,采用随机、盲法,同类疫苗对照方法,对600名1.5～15岁儿童和600名成人按照2:1比例,各400人接种试验疫苗(儿童或成人剂量甲型肝炎灭活疫苗)和200人接种对照疫苗(市售同类儿童或成人剂量甲型肝炎灭活疫苗),免疫程序为0、6月;观察接种后局部反应和全身反应;采用EIA竞争抑制法检测免疫前后的甲型肝炎抗体,以WHO甲肝免疫球蛋白(含100IU/ml)标准品进行标定,计算免疫后的甲型肝炎抗体阳转率和抗体几何平均滴度(mIU/ml).结果 两剂量组试验疫苗与对照疫苗的局部反应和全身反应相似,局部反应以注射部位疼痛多主,全身反应以轻度发热反应较常见.试验疫苗儿童剂量组和成人剂量组甲肝抗体阳转率分别为98.53%和97.55%,甲肝抗体几何平均滴度分别为10 332.32 mIU/ml和9 473.65 mIU/ml,与对照组比较均无显著差异.结论 新型甲肝灭活疫苗(Vero细胞)儿童剂量(800EU/ml)和成人剂量(1 600EU/ml)对儿童或成人接种的安全性良好,并可诱导高度的抗HAV阳转率和抗体水平.     

乙型肝炎病毒基因疫苗联合抗原蛋白免疫效应的评价

目的探讨乙型肝炎病毒(HBV)基因疫苗联合乙型肝炎病毒表面抗原S蛋白(HBsAg)免疫Balb/c小鼠的效应.方法构建编码S蛋白的重组真核表达质粒pCR3.1-S作为HBV基因疫苗.以HBV基因疫苗联合HBsAg蛋白免疫接种Balb/c小鼠,同时以HBV基因疫苗或S蛋白单独接种Balb/c小鼠作为对照.采用ELISA法检测免疫小鼠的抗HBs应答,3H-TdR掺入法检测免疫小鼠的淋巴细胞增殖反应.结果免疫接种2周、4周后,联合免疫组抗HBs滴度高于HBV基因疫苗单独接种组,但低于S蛋白单独接种组;6周后,HBV基因疫苗组抗HBs滴度最高,联合组次之.各组间免疫小鼠的淋巴细胞增殖反应无显著差异性(P＞0.05).结论 HBV基因疫苗联合S蛋白免疫Balb/c小鼠无优势.     

Onjisaponins, from the root of Polygala tenuifolia Willdenow, as effective adjuvants for nasal influenza and diphtheria-pertussis-tetanus vaccines

Active substances from hot water extracts from 267 different Chinese and Japanese medicinal herbs were screened for mucosal adjuvant activity with influenza HA vaccine in mice. The extract from the root of Polygala tenuifolia was found to contain potent mucosal adjuvant activity. The active substances were purified and identified as onjisaponins A, E, F, and G. When each onjisaponin (10 μg) was intranasally (i.n.) inoculated with influenza vaccine (10 μg) in mice, serum hemagglutination-inhibiting (HI) antibody titers increased 3–14 times over control mice administered vaccine alone after 4 weeks. When each onjisaponin (10 μg) was i.n. inoculated with the vaccine (10 μg) followed by i.n. vaccination of the vaccine alone after 3 weeks, serum HI antibody titers increased 27–50 fold over those mice given i.n. vaccinations without onjisaponins. These same conditions also significantly increased nasal anti-influenza virus IgA antibody titers. Two inoculations with onjisaponin F (1 μg) and influenza HA vaccine (1 μg) at 3 weeks intervals, significantly increased serum HI antibody and nasal anti-influenza virus IgA and IgG antibody titers after only 1 week over mice given HA vaccine alone after the secondary vaccination. Intranasal vaccination with onjisaponin F inhibited proliferation of mouse adapted influenza virus A/PR/8/34 in bronchoalveolar lavages of infected mice. Separate intranasal vaccinations with onjisaponins A, E, F, and G (10 μg) each and diphtheria–pertussis–tetanus (DPT) vaccine (10 μg) of mice followed by i.n. vaccination with DPT vaccine alone after 4 weeks showed significant increases in serum IgG and nasal IgA antibody titers after 2 weeks following secondary vaccination over mice vaccinated with DPT vaccine alone. All onjisaponins showed little hemolytic activity at concentrations up to 100 μg/ml. The results of this study suggest that onjisaponins may provide safe and potent adjuvants for intranasal inoculation of influenza HA and DPT vaccines.     

Onjisaponins, from the root of Polygala tenuifolia Willdenow, as effective adjuvants for nasal influenza and diphtheria–pertussis–tetanus vaccines

Active substances from hot water extracts from 267 different Chinese and Japanese medicinal herbs were screened for mucosal adjuvant activity with influenza HA vaccine in mice. The extract from the root of Polygala tenuifolia was found to contain potent mucosal adjuvant activity. The active substances were purified and identified as onjisaponins A, E, F, and G. When each onjisaponin (10 μg) was intranasally (i.n.) inoculated with influenza vaccine (10 μg) in mice, serum hemagglutination-inhibiting (HI) antibody titers increased 3–14 times over control mice administered vaccine alone after 4 weeks. When each onjisaponin (10 μg) was i.n. inoculated with the vaccine (10 μg) followed by i.n. vaccination of the vaccine alone after 3 weeks, serum HI antibody titers increased 27–50 fold over those mice given i.n. vaccinations without onjisaponins. These same conditions also significantly increased nasal anti-influenza virus IgA antibody titers. Two inoculations with onjisaponin F (1 μg) and influenza HA vaccine (1 μg) at 3 weeks intervals, significantly increased serum HI antibody and nasal anti-influenza virus IgA and IgG antibody titers after only 1 week over mice given HA vaccine alone after the secondary vaccination. Intranasal vaccination with onjisaponin F inhibited proliferation of mouse adapted influenza virus A/PR/8/34 in bronchoalveolar lavages of infected mice. Separate intranasal vaccinations with onjisaponins A, E, F, and G (10 μg) each and diphtheria–pertussis–tetanus (DPT) vaccine (10 μg) of mice followed by i.n. vaccination with DPT vaccine alone after 4 weeks showed significant increases in serum IgG and nasal IgA antibody titers after 2 weeks following secondary vaccination over mice vaccinated with DPT vaccine alone. All onjisaponins showed little hemolytic activity at concentrations up to 100 μg/ml. The results of this study suggest that onjisaponins may provide safe and potent adjuvants for intranasal inoculation of influenza HA and DPT vaccines.     

Head-to-head comparison of four nonadjuvanted inactivated cell culture-derived influenza vaccines: effect of composition, spatial organization and immunization route on the immunogenicity in a murine challenge model

In order to study the influence of antigen composition, spatial organization of antigen and the route of administration, four cell culture-derived, inactivated, nonadjuvanted influenza vaccine formulations, i.e. whole inactivated virus (WIV), split, subunit and virosome vaccines were prepared from a single antigen batch. We directly compared the immunogenicity and efficacy of these vaccine formulations after intramuscular (i.m.) or intranasal (i.n.) administration in mice. Prime and boost vaccination were followed by a potentially lethal homologous aerosol challenge. For all vaccines, the i.m. route induced higher serum humoral immune responses as compared to the i.n. route and protected all mice against challenge at a dose of 5 microg. Upon i.n. immunization only WIV and split vaccines induced detectable IgG titers and partial protection against challenge but only very low HI titers were induced in almost all mice. WIV induced mainly IgG2a/c titers via both routes, whereas split vaccine induced exclusively IgG1 titers via both routes. Subunit and virosome vaccines induced exclusively IgG1 via the i.m. route. Mucosal sIgA levels were only detected after i.n. vaccination with WIV. Furthermore, vaccines containing all viral components (WIV and split vaccine) induced higher serum HI titers and serum antibody titers than subunit and virosome vaccines. The differences in magnitude and quality of immune responses of split and WIV, having the same composition, are likely related to their distinct spatial organization. In conclusion, the direct comparison between WIV, split, subunit and virosomes, shows that the differences in immune responses between these well known influenza vaccines can be explained by both the composition and particulate structure of these vaccine formulations.     

628例接种人用纯化地鼠肾细胞狂犬疫苗者血清IgG抗体水平调查

目的了解人用纯化地鼠肾细胞狂犬疫苗的免疫接种效果。方法收集2009年1月-2011年12月接种人用地鼠肾细胞狂犬纯化疫苗628人的流行病学资料,并分别采集接种疫苗后第7 d和第15 d的血清标本。用ELISA方法检测血清IgG抗体,对不同性别、不同年龄组和接种后不同时间的血清抗体水平进行比较分析。结果共检测疫苗接种人群628人,免疫后7 d和15 d的IgG抗体阳性率分别为59.71%和94.11%,经χ2检验,两者间差异有统计学意义(P<0.01)。10岁以下年龄组接种人群无论是接种7 d还是接种15 d的血清IgG抗体阳性率高于60岁以上年龄组(P<0.05)。不同性别免疫接种7 d后与免疫接种15 d后的IgG抗体阳性率间差异无统计学意义(P>0.05)。结论接种人用纯化地鼠肾细胞狂犬疫苗的人群IgG抗体阳性率与接种人群的年龄、接种后的时间相关,接种后15 d的IgG抗体阳性率达到94.11%,60岁以上年龄组的IgG抗体阳性率明显低于10岁以下年龄组。     

An in vivo passive protection assay for the evaluation of immunity in AVA-vaccinated individuals

Samples of human plasma from anthrax vaccine adsorbed (AVA, BioThrax)-vaccinated individuals were used to demonstrate passive protection of A/J mice from a lethal challenge with the Sterne strain of anthrax bacteria. The maximum concentration of human anti-protective antigen IgG in mouse sera 24 h after injection of 260 microg of anti-PA IgG was 134 microg/ml, declining to 91 microg/ml at 72 h (half-life=101.7 h). Mice showed significant survival (p相似文献   

Antibody response to a delayed booster dose of anthrax vaccine and botulinum toxoid

We evaluated the prevalence and concentration of serum antibodies 18-24 months after primary inoculation with anthrax and botulinum vaccines, and assessed the reactogenicity and immunogenicity of a significantly delayed booster dose of these vaccines. Five hundred and eight male active-duty military personnel received one, two or three inoculations with anthrax vaccine and/or botulinum toxoid in 1990/1991 in preparation for Operations Desert Shield/Desert Storm. Subjects were vaccinated with the licensed anthrax vaccine, adsorbed (AVA) and pentavalent (ABCDE) botulinum toxoid (PBT) BB-IND 3723. Anthrax protective antigen (PA) IgG antibody was measured in serum using an immunocapture enzyme-linked immunosorbent assay (ELISA). A mouse neutralization test was used to determine the titer of Clostridium botulinum type A antitoxin in serum samples. The prevalence of anti-PA IgG was 30% in individuals 18-24 months after priming with one, two or three doses of AVA. After boosting, 99% of volunteers had detectable anti-PA IgG; only two individuals failed to respond. The prevalence of antibodies against botulinum toxin type A was 28% 18-24 months after initial priming. Following boosting, 99% of volunteers had serum titers >0.02IU/ml, and 97% responded with titers > or =0.25IU/ml.Systemic reactions to booster vaccinations could not be specifically ascribed to one or the other vaccine, but were generally mild and of brief duration. Forty-five percent of volunteers reported one or more systemic reactions over the course of 7 days. Injection site reactions of any kind occurred in 25% of AVA recipients and in 16% of PBT recipients; persistence of local reactions beyond 7 days was infrequent.While the kinetics and durability of immune responses must be studied, these findings suggest that booster doses of anthrax vaccine and botulinum toxoid sufficient to stimulate a robust anamnestic response may be given at times distant from receipt of the primary inoculations.     

Immunogenicity and Protective Efficacy of Recombinant Protective Antigen Anthrax Vaccine (GC1109) in A/J Mice Model

A recombinant protective antigen anthrax vaccine (GC1109) is being developed as a new-generation vaccine by the Korea Disease Control and Prevention Agency. In accordance with the ongoing step 2 of phase II clinical trials, the immunogenicity and protective efficacy of the booster dose of GC1109 were evaluated in A/J mice after 3 serial vaccinations at 4-week intervals. The results indicated that the booster dose significantly increased the production of anti-protective antigen (PA) IgG and toxin-neutralizing antibody (TNA) compared with those of the group without booster. An enhanced protective effect of the booster dose was not observed because the TNA titers of the group without booster were high enough to confer protection against spore challenge. Additionally, the correlation between TNA titers and probability of survival was determined for calculating the threshold TNA titer levels associated with protection. The threshold 50 % neutralization factor (NF₅₀) of TNA showing 70 % probability of protection was 0.21 in A/J mice with 1,200 LD₅₀ Sterne spores challenge. These results indicate that GC1109 is a promising candidate as a new-generation anthrax vaccine and that a booster dose might provide enhanced protection by producing toxin-neutralizing antibodies.     

Selection and evaluation of the immunogenicity of protective antigen mutants as anthrax vaccine candidates

Protective antigen (PA) is a central component of anthrax toxin and a major antigen in anthrax vaccines. However, the use of native PA as a vaccine is not optimal. If administered to people who have been freshly exposed to anthrax, PA may actually aid in anthrax toxin formation and thus may pose a serious safety concern for postexposure vaccination applications. A non-functional PA mutant may be a much safer alternative. To identify an improved anthrax vaccine antigen, we examined four non-functional mutants of PA, each being impaired in a critical step of the cellular intoxication pathway of PA. These mutants were Rec(-) (unable to bind PA-receptors), SSSR (resistant to activation by furin), Oligo(-) (unable to form oligomers), and DNI (Dominant Negative Inhibitory, unable to form endosomal transmembrane pores). When tested in mice and after three doses of immunization, all four mutants were highly potent in eliciting PA-specific, toxin-neutralizing antibodies, with immunogenicity increasing in the order of PA相似文献