国产与进口冻干无佐剂人用狂犬病疫苗的安全性和免疫原性比较

目的评价国产冻干人用无佐剂狂犬病纯化疫苗(Vero细胞)的安全性和免疫原性。方法对600名健康人随机分为两组,480人(A组)接种冻干无佐剂人用狂犬病纯化疫苗(Vero细胞)和120人(B组)作为对照接种巴斯德公司生产的冻干无佐剂狂犬病纯化疫苗,采用0、3、7、14和28天免疫程序。观察每针次接种后72小时内局部和全身反应及14天、45天的免疫应答水平。结果所有接种对象均未出现严重局部和全身副反应。首剂免疫14天,A、B组抗体阳性率分别均达到98.06%和96.49%,几何平均滴度为5.0IU/ml和3.79IU/ml。免疫后45天,A、B组抗体阳性率均达到100%,抗体几何平均滴度分别上升至7.97IU/ml和7.61IU/ml。结论国产人用狂犬病无佐剂纯化疫苗(Vero细胞)具有良好安全性和免疫原性。     

53例人用狂犬病无佐剂纯化疫苗接种后抗体检测结果分析

目的观察暴露后人群接种国产人用狂犬病无佐剂纯化疫苗(Vero cell)的免疫效果。方法对53例研究对象按照0、3、7、14和28 d程序进行暴露后免疫,采用WHO认可的RFFIT法检测免疫14 d,45 d的血清抗体。观察每针次接种后72 h内局部和全身反应。结果所有接种对象均未出现严重副反应。首剂免疫14 d,45 d ELISA法检测抗体阳性率分别为52.83%,94.34%,RFFIT法检测抗体阳性率分别为100%,100%。几何平均滴度(GMT)为17.74 IU/ml,15.50 IU/ml。结论国产人用狂犬病无佐剂纯化疫苗(Vero cell)具有良好的安全性和免疫原性。     

国产液体无佐剂狂犬病疫苗免疫应答动态观察

目的评价国产液体无佐剂非洲绿猴肾(Vero)细胞狂犬病疫苗的免疫原性。方法 选择既往无明确狂犬病疫苗接种史和犬伤史,符合研究方案制定的入选标准和排除标准,对暴露于狂犬病患者采用常规5针注射。观察对象于首针接种前,首针接种后7、14、28、45 d,全程后180 d采集血样检测抗狂犬病中和抗体。结果符合入选标准和排除标准的观察对象120名常规接种5针液体无佐剂Vero细胞狂犬病疫苗。观察对象接种前狂犬病抗体均为阴性,接种首针后7 d狂犬病抗体阳转率为10.83%,接种首针后14 d阳转率达到100%,接种首针后28 d、45 d和全程后6个月的阳性率均为100%。接种首针后7 d狂犬病抗体几何平均滴度(GMT)仅为0.08 IU/ml,接种首针后14 d狂犬病抗体的GMT达到1.02 IU/ml,较首针接种后7 d增长12.75倍。接种首针后28、45 d狂犬病抗体的GMT分别达到4.93 IU/ml、9.71 IU/ml,较首针后14 d分别增长4.83倍、9.52倍。全程接种后6个月狂犬病抗体的GMT仍达到6.25 IU/ml。结论国产液体无佐剂Vero细胞狂犬病疫苗具有良好的免疫原性,6个月内再被暴露于狂犬病动物者可以不需要接种狂犬病疫苗。     

无佐剂Vero细胞狂犬病纯化疫苗的接种反应及免疫效果观察

目的观察无佐剂Vero细胞狂犬病纯化疫苗接种反应及其免疫效果。方法对被犬、猫所伤的785人按暴露后免疫程序接种,观察每剂次接种反应及完成接种程序后14天免疫效果。结果所有接种对象均未发生即时反应,未出现异常和全身强副反应;完成免疫程序后14天抗体阳转率99.8%。结论无佐剂Vero细胞狂犬病纯化疫苗具有良好的安全性和免疫原性。     

人用Vero细胞狂犬病疫苗暴露前免疫的安全性和免疫效果观察

目的为观察人用Vero细胞狂犬病疫苗暴露前免疫程序的安全性和效果。方法征集志愿者65人,暴露前接种3剂人用Vero细胞狂犬病疫苗,分别于第0d、7d、28d肌内注射。次年第1针免疫后的第365d加强1剂。用小鼠脑内中和试验测定其抗狂犬病病毒抗体。结果所有志愿者均未出现局部反应、全身反应和严重不良反应。65名志愿者在第1次接种前,除1名血清抗体为0.5IU/ml外,其余均未测出抗体。第45d、365d、385d的血清抗体阳转率分别为100.00%、90.57%、100.00%,几何平均滴度分别为12.82IU/ml、1.57IU/ml、40.49IU/ml。结论人用Vero细胞狂犬病疫苗在暴露前免疫程序安全且效果好。     

精制Vero细胞狂犬病疫苗的研制及免疫学效果观察

目的　以Vero细胞为基质，研制新一代精制Vero细胞狂犬病疫苗。方法　以CTN-1V10为生产毒株，以＜150代Vero细胞为培养基质，采用转瓶旋转培养，按不同时间收获病毒液，经过澄清、浓缩、纯化、灭活制成精制Vero细胞狂犬病疫苗。从以此工艺制备的疫苗中选取一批做为免疫学效果观察的受试疫苗。按暴露后免疫程序接种63人，其中受试疫苗接种33人，法国维尔博狂犬病疫苗接种30人，观察不良反应和测定中和抗体。结果　新研制的精制Vero细胞狂犬病疫苗各项指标完全符合WHO的有关质量要求。两种疫苗全程免疫后中和抗体阳转率均为100%，中和抗体受试组为11.94IU/ml;维尔博疫苗对照组为11.69IU/ml。结论　精制Vero细胞狂犬病疫苗不但制造工艺合理，而且副反应轻微，免疫原性良好。     

冻干无佐剂Vero细胞CTN狂犬病疫苗安全性和免疫原性研究

目的 观察人用冻干狂犬病疫苗(Vero细胞/CTN疫苗株)的安全性、免疫原性和抗体持久性.方法 对450名健康志愿者随机分为2组,300人(试验组)接种人用冻干狂犬病疫苗(Vero细胞/CTN疫苗株),150人(对照组)接种进口冻干无佐剂狂犬病纯化疫苗;按照0、3、7、14、28 d免疫程序;观察每针次接种后局部和全身反应.采用快速荧光灶抑制试验(RFFIT)检测0(首剂接种前)、3、7、14、28d血清中和抗体水平(GMT).首剂免疫后365 d采集试验组血样本212份,对照组血样本97份;首剂免疫后730 d采集试验组血样本176份,对照组血样本80份,RFFIT检测GMT.结果 所有接种对象均未出现严重局部和全身反应.首剂免疫后3、7、14、28、365和730 d试验组抗体阳转率分别为2.35%、80.78%、100.00%、100.00%、98.58%和73.30%;GMT分别为0.12、1.01、9.83、12.61、3.68和2.81 IU/ml.首剂免疫后3、7、14、28、365和730 d对照组抗体阳转率分别为4.00%、87.20%、100.00%、100.00%、97.94%和76.25%;GMT分别为0.13、1.18、10.24、11.61、4.18和1.92 IU/ml.所有结果试验组与对照组相比差异无统计学意义(P＞0.05).结论 人用冻干狂犬病疫苗具有良好的安全性、免疫原性和抗体持久性.     

一种国产人用狂犬病疫苗(Vero细胞)的免疫原性与安全性评价

目的 评价一种国产人用狂犬病疫苗(Vero细胞)用于10～60岁健康人群的免疫原性和安全性。 方法 单中心、随机、双盲、同类制品平行对照、模拟暴露后免疫的非劣效性研究。采用“Essen”免疫程序,选择10～60岁健康人群,按照1∶1比例随机接种试验疫苗和对照疫苗,使用日记卡收集每针次接种后不良反应情况。采集免前、首针免后第14天和第42天血液标本,用快速荧光灶抑制试验(RFFIT)检测血清中狂犬病毒中和抗体水平。 结果 试验组和对照组各入组600人。首针免后第42天和第14天,抗体阳转率均达到100%;抗体几何平均浓度(GMC)试验组为13.00IU/ml和7.89IU/ml,对照组为15.03IU/ml和10.20IU/ml,差异有统计学意义。总体征集性不良反应发生率试验组和对照组分别为60.33%和65.67%,差异无统计学意义。总体全身不良反应发生率对照组(46.17%)高于试验组(39.83%),前3针次不良反应发生率对照组(25.17%、16.13%、27.97%)均高于试验组(17.83%、11.80%、22.24%),差异有统计学意义。 结论 长春卫尔赛生物药业有限公司研制的人用狂犬病疫苗(Vero细胞)在10～60岁健康人群中具有较好的免疫原性和安全性。     

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.     

不同细胞基质狂犬疫苗接种后的安全性及免疫原性评价

目的 了解两种细胞基质狂犬疫苗接种后的安全性及免疫原性，并对其进行评价。方法 选择2019年6月至2022年6月在我院门诊部接种狂犬疫苗的2 292例患者作为研究对象，首剂疫苗接种后通过电话随访的形式随访45 d，失访23例，共2 269例完成所有接种和随访，根据接种意愿不同分为Vero组(接种Vero细胞狂犬疫苗)、二倍体组(接种人二倍体细胞狂犬疫苗)。按照0、3、7、14、28 d完成接种，并观察首剂疫苗接种后45 d随访期内不良反应情况，分析329例全程接种前、全程接种后14 d和45 d血清狂犬病毒中和抗体滴度，计算几何平均浓度水平(GMC)。结果 二倍体组局部反应中的疼痛和瘙痒、全身反应中的发热、无力和头痛发生率均低于Vero组(P<0.05)。329例进行免疫观察的患者中，Vero组(n=144)和二倍体组(n=187)全程接种后14 d、45 d抗体阳性率均为100.00%；二倍体组14 d、45 d的GMC(9.28 IU/mL、22.74 IU/mL)高于Vero组(8.41 IU/mL、21.39 IU/mL)，差异有统计学意义(P<0.05)。结论 两...     

Safety and immunogenicity of two freeze-dried Vero cell rabies vaccines for human use in post-exposure prophylaxis

To provide basis for human rabies vaccination in China, the safety and immunogenicity of two freeze-dried Vero cell rabies vaccines for human use were assessed. A total of 250 volunteers were enrolled and divided into two groups: volunteers in Group A (n = 200) were vaccinated five doses of Speeda Vero cell rabies vaccine manufactured by Liaoning Chengda Biotechnology Co. Ltd. on day 0, 3, 7, 14, 28 after exposure. Volunteers in Group B (n = 50) were treated with Verorab Vero cell rabies vaccine manufactured by Sanofi Pasteur on the same schedule. The local and systematic adverse reactions were observed. Serum neutralizing antibody levels of 80 individuals in Group A and 50 individuals in Group B were tested with RFFIT on day 7, 14, 45, 180, 360 after the first dose. The seroconversion rates in Groups A and B were 40.3% and 37.0% on day 7 after the first dose, 95.5% and 97.7% on day 14, 100% and 100% on day 45, 100% and 100% on day 180, 89.1% and 89.5% on day 360 respectively, indicating no significant differences between the two groups. And no significant differences were found between the neutralizing antibody geometric mean titers (GMTs) of the two groups on day 7, 14, 45, 180 and 360 after the first dose, with the GMTs of day 14, 45, 180 and 360 all higher than 0.5 IU/ml. Antibody levels of the two groups peaked around 2 weeks after the full vaccination program, followed by a 55% decrease up to day 180 and another 76% decrease up to day 360. Both groups experienced occasions of transient fever, rash, edema, and scleroma after vaccination. Neither group had any severe adverse reactions. It was concluded that both vaccines showed satisfactory safety and immunogenicity. Booster vaccination is recommended following another exposure after six months since the full vaccination program.     

国产甲型肝炎灭活疫苗的安全性与免疫原性初步观察

目的 评价国产甲型肝炎灭活疫苗的安全性和免疫原性。方法 对健康易感儿童1％名和成人206名随机分为4组，107名儿童(A组)和131名成人(B组)接种国产甲肝灭活疫苗，另69名儿童(c组)和75名成人(D组)作为对照接种史克必成公司生产的甲肝灭活疫苗。国产疫苗剂量为儿童640EIU／1．0ml。成人1440EIU／1．0ml，对照疫苗剂量儿童720EIU／1．0ml，成人1440EIU／1．0ml，均采用0、6程序。观察72小时内局部和全身反应及免后1、6、7月的免疫应答水平。结果 所有接种对象均未出现明显局部和全身副反应，亦未发现免后ALT升高。初免后一个月A组和B组抗体阳性率分别为94．8％和96．7％，几何平均滴度为758．6mIU／ml和3630．8mIU／ml。全程免疫后一个月4组抗体阳性率均为100％，A组和B组抗体几何平均滴度上升至10471．2mIU／ml和12302．7mIU／m1，略高于对照的C组和D组(分别为3090．3mIU／d和3388．4mIU／ml)。结论 国产甲肝灭活疫苗具有良好安全性和免疫原性。     

成人和儿童接种国产甲型肝炎灭活疫苗的安全性与免疫原性的初步观察

为了评价国产甲型肝炎 (甲肝 )灭活疫苗的安全性和免疫原性 ,将 176名健康易感儿童和 2 0 6名成人随机分为 4组 ,10 7名儿童 (A组 )和 131名成人 (B组 )接种国产甲肝灭活疫苗 ,另 6 9名儿童 (C组 )和 75名成人 (D组 )作为对照接种史克必成公司生产的甲肝灭活疫苗。国产疫苗剂量为儿童 6 4 0EU/1 0ml,成人 12 80EU/1 0ml;对照疫苗剂量儿童 72 0EIU/1 0ml,成人 14 4 0EIU/1 0ml,均采用 0、6个月免疫程序。观察 72h内局部和全身反应 ,免疫后 1、6、7个月的免疫应答水平。结果显示 :所有接种对象均未出现明显的局部和全身副反应 ,亦未发现免疫后丙氨酸氨基转移酶 (ALT)升高。初次免疫后 1个月 ,A组和B组抗体阳转率分别为 94 8%和 96 7% ,几何平均滴度(GMT)为 75 8 6mIU/ml和 36 30 8mIU/ml。全程免疫后 1个月 ,4个组抗体阳转率均为 10 0 % ,A组和B组抗体GMT升至 10 4 71 2mIU/ml和 12 30 2 7mIU/ml,略高于对照的C组和D组 (分别为 30 90 3mIU/ml和3388 4mIU/ml)。表明国产甲肝灭活疫苗具有良好安全性和免疫原性。     

A randomized open-label trial of 2-dose or 3-dose pre-exposure rabies prophylaxis among Thai children

BackgroundWorld Health Organization changed the recommendation for pre-exposure rabies prophylaxis from 3-dose to 2-dose regimen in 2018. Given limited data of 2-dose regimens in pediatric population, this study aimed to compare the immunogenicity between 2-dose and 3-dose pre-exposure rabies immunization.MethodsThis study was conducted among healthy children aged 2–12 years. They were randomized to 2-dose vaccination (2D) on days 0 and 28 or 3-dose vaccination (3D) on days 0, 7, and 28. Purified Vero cell rabies vaccine (PVRV-Verorab™) was administered intramuscularly. Rabies virus neutralizing antibody (RVNA) titers were measured at 3 time points: 14-day after complete vaccination, 1-year pre-booster vaccination, and 7-day post-booster dose to mimic scenario of rabies exposure. RVNA titers ≥0.5 IU/ml were considered adequate antibody. T cell specific response to rabies vaccine antigen was measured using the interferon-gamma enzyme linked immunospot assay.ResultsFrom September to October 2017, 107 participants (51% males), 78 in 2D group and 29 in 3D group were enrolled. Median age was 5.8 years (IQR 4.4–7.3). All participants had RVNA titers ≥0.5 IU/ml after primary vaccination [GMT 2D: 18.6 (95%CI 15.9–21.8) and 3D: 16.3 (95%CI 13.2–20.1 IU/ml), p = 0.35]. At 1-year prior to receiving the booster, only 80% of the children in 2D group maintained RVNA titers ≥0.5 IU/ml compared to 100% of the children in 3D group (p = 0.01). However, all participants in both groups had RVNA ≥0.5 IU/ml at 7-day post booster vaccination [GMT 2D: 20.9 (95%CI 17.4–25.3) and 3D: 22.2 (95%CI 15.8–31.4) IU/ml (P = 0.75)]. The median number of IFN-γ secreting cells at 7-day post-booster dose was 98 and 128 SFCs per 10⁶ PBMCs in the 2D and 3D groups, respectively (P = 0.30).ConclusionsTwo-dose primary rabies immunization provided adequate antibody at post primary vaccination and post booster. The results support 2-dose regimen of pre-exposure rabies immunization in the pediatric population.     

Rabies neutralizing antibody after 2 intradermal doses on days 0 and 21 for pre-exposure prophylaxis

Pre-exposure prophylaxis is recommended for people who will be exposed to rabies virus in the laboratory or who will contact with mammals. World Health Organization recommends 2 doses of a cell-culture rabies vaccine given 1 week apart, and a third booster dose given 2–3 weeks later. Neutralizing antibody response is virtually 100%, and the individual remains sensitized indefinitely. Intradermal pre-exposure regimen for rabies prophylaxis is more economical compared with the conventional intramuscular regimen in terms of vaccine volume. However, both regimens require three clinic visits. In order to reduce non-medical expenses such as transportation to the clinics and to increase compliance, the immunogenicity and safety of two-visit intradermal regimen for pre-exposure prophylaxis were studied. Fifty-five healthy subjects aged between 18 and 24 years were enrolled and divided into two groups. Group A (n = 39) received 0.1 ml of purified Vero cell rabies vaccine (PVRV; Sanofi Pasteur, Lyon, France; Lot no. Z0996 with an antigenic value of 4.8 IU/0.5 ml vial) intradermally each at two sites on days 0 and 21. Group B (n = 16) received 0.5 ml of PVRV intramuscularly on days 0, 7 and 21, as conventional intramuscular regimen for pre-exposure prophylaxis. Rabies neutralizing antibody (Nab) titers were measured on days 0, 35, 365 and 379 (14 days after simulated post-exposure booster vaccination). All subjects from two groups had Nab titers ≥0.5 IU/ml on day 35. In addition, the difference between geometric mean titers for group A (4.51 IU/ml; range of Nab titers 1.69–13.0 IU/ml) and group B (6.74 IU/ml; range of Nab titers 2.20–14.23 IU/ml) on day 35 was not statistically significant (p > 0.05). One year after pre-exposure vaccination, all subjects in both groups received simulated post-exposure booster vaccination with 0.1 ml of PVRV ID on days 0 and 3 (day 365 and day 368 after pre-exposure vaccination). After simulated booster vaccinations with 0.1 ml PVRV ID on days 0 and 3, all subjects in groups A (GMT 14.38 IU/ml; range 2.99–308.44 IU/ml) and in group B (GMT 14.06 IU/ml; range 3.12–62.09 IU/ml) had rabies Nab titers ≥0.5 IU/ml on day 14 post-booster (p > 0.05). Mild local adverse events such as pain at injection site, pruritus and erythema were observed. Our study indicated that 2-site intradermal pre-exposure regimen on days 0 and 21 with 0.1 ml of cell-culture rabies vaccine is safe and immunogenic as the conventional intramuscular regimen.     

Immune response to rabies vaccine in Thai dogs: a preliminary report

Serum neutralizing antibody to rabies virus was determined in previously unvaccinated Thai pet dogs after receiving one subcutaneous dose of inactivated tissue culture rabies vaccine (Rabdomun, Coopers Animal Health Company, Germany, 4.55 IU ml-1 potency). Geometric mean titres on days 14, 30, 60, 180 and 360 were 2.14, 2.30, 0.45, 0.14 and 0.05 IU ml-1, respectively, by the rapid immunofluorescent focus inhibition test. Titres of neutralizing antibody to rabies virus did not correlate with the age of the dog at the time of vaccination or with the presence or absence of anaemia or blood parasites. Six out of 50 (12%), 11 out of 43 (25.6%) and 13 out of 31 (42%) dogs had no detectable rabies antibody in serum 60, 180 and 360 days, respectively, after vaccination. Three of these antibody-negative dogs were given another dose of vaccine. Antibody reappeared on day 14 but rapidly declined within 60 days. These data suggest that one dose of tissue culture vaccine in dogs by the subcutaneous route of injection is not adequate to maintain rabies neutralizing antibody in serum for 1 year.     

孩尔来福甲型肝炎灭活疫苗0,12个月免疫程序研究

目的　对孩尔来福 (HealiveR○)甲型肝炎 (甲肝 )灭活疫苗的安全性、免疫原性及适宜儿童的剂量进行研究。方法　在某山区两个农村筛选 4～ 10岁甲肝病毒抗体 (抗 HAV)阴性的 85名易感儿童。以自然村随机分为两组 ,按 0 ,12个月免疫程序分别接种北京科兴生物制品有限公司生产的每剂 2 50U 0 .5ml和 50 0U 1ml甲肝灭活疫苗 ,观察免疫后局部反应和全身反应 ,检测初次免疫 (初免 )后 2 1天、12个月及全程免疫后 1个月抗 HAV阳转率和抗体几何平均滴度 (GMT )。结果　两组均未见严重局部反应和全身反应 ;2 50U 0 .5ml组和 50 0U 1ml组初免后 2 1天 ,抗 HAV阳转率分别为94.4%和 10 0 .0 % ,GMT分别为 195mIU ml和 3 70mIU ml ;初免后 12个月抗 HAV全部阳转 ,GMT分别达 3 61mIU ml和 456mIU ml(P >0 .0 5) ;全程免疫后 1个月 ,GMT分别达 14 893mIU ml和2 1696mIU ml。结论　孩尔来福甲肝灭活疫苗的安全性和免疫原性好 ;每剂 2 50U 0 .5ml适宜儿童 ;0 ,12个月免疫程序更适宜中国儿童