麻疹-腮腺炎-风疹联合减毒活疫苗生产场地变更的质量可比性研究

目的  比较生产场地变更前后生产的麻疹-腮腺炎-风疹联合减毒活疫苗（麻腮风疫苗）的关键质量指标及其变化趋势。 方法   新老车间同步各生产3批麻腮风疫苗,比较新老车间生产的疫苗的关键指标及其变化趋势,同时对新老车间生产的疫苗进行稳定性和安全性比较研究。 结果   新老车间生产的疫苗成品的关键质量指标均符合相关规定的要求,其中新车间生产的疫苗的水分为1.6%~1.8%,其麻疹、腮腺炎和风疹病毒滴度分别为4.1~4.3、4.8~5.0 和3.9~4.1 lgCCID₅₀/ml,与老车间生产的疫苗（水分为1.6%~2.1%,麻疹、腮腺炎和风疹病毒滴度分别4.0~4.3、4.8~5.0和4.1~4.2 lgCCID₅₀/ml）相似。新老车间生产的疫苗成品的稳定性和安全性实验结果均符合相关规定的要求,且新老车间生产的疫苗的稳定性实验结果相似,新老车间生产的疫苗的抗生素残留量（t＝3.46,P>0.05）和牛血清白蛋白残留量（t＝2.00,P>0.05）间的差异无统计学意义。 结论   麻腮风疫苗生产场地变更未对其制品质量产生影响。     

麻疹、腮腺炎、风疹、水痘联合减毒活疫苗的生产工艺研究

目的  建立麻疹、腮腺炎、风疹、水痘联合减毒活疫苗（combined live attenuated measles，mumps，rubella and varicella vaccine，MMRV）的生产工艺。方法  根据现有疫苗病毒原液生产工艺，将麻疹病毒沪-191纯化株、腮腺炎病毒S79株、风疹病毒BRD-Ⅱ株和水痘-带状疱疹病毒Oka株在原代鸡胚成纤维细胞或人二倍体细胞MRC-5株中制备高滴度病毒原液，并超低温保存。筛选无明胶冻干稳定剂配方。按国外已上市同类产品的病毒配比，研究MMRV中4种病毒的原液配制滴度及成品配制比例，建立最佳冻干工艺。结果  用筛选出的适合于MMRV的无明胶冻干稳定剂配方进行试验，确定病毒原液的配制滴度为，麻疹4.6 lg半数细胞培养感染量（50% cell culture infective dose，CCID₅₀）/ml、腮腺炎5.8 lgCCID₅₀/ml、风疹4.3 lgCCID₅₀/ml、水痘4.8 lg噬斑形成单位（plaque forming unit，PFU）/ml。使成品中腮腺炎病毒滴度至少达到麻疹和风疹和水痘病毒的10倍，水痘病毒滴度高于现有单价水痘疫苗。连续制备3批MMRV，平均病毒滴度为，麻疹4.5 lgCCID₅₀/ml、腮腺炎5.1 lgCCID₅₀/ml、风疹4.3 lgCCID₅₀/ml、水痘4.6 lgPFU/ml；平均水分为1.2%。其他项目检定均合格。结论  建立了MMRV的生产工艺，可以稳定生产出达到国外同类产品质量标准并符合我国4种单价减毒活疫苗国家标准的产品。     

麻疹、腮腺炎、风疹和水痘联合减毒活疫苗中水痘病毒滴度测定方法研究

目的 建立并验证麻疹、腮腺炎、风疹和水痘(measles,mumps,rubella and varicella,MMRV)联合减毒活疫苗中水痘病毒滴度的测定方法.方法 首先通过比较温度,确定中和条件;再根据抗麻疹、腮腺炎、风疹病毒血清对相应病毒的完全中和能力,确定每种抗血清的使用浓度.观察抗血清对2BS细胞生长的影响和对水痘病毒的干扰作用.采用t检验对结果进行比较.结果 与37℃1h相比,4℃1h的中和条件能准确反映MMRV疫苗中水痘病毒的滴度水平(t=6.7082,P＜0.01).3种抗血清(麻疹1∶80、腮腺炎1∶40、风疹1∶40)混合后对2BS细胞生长无影响,对不同滴度水痘病毒无干扰(高滴度t=0.4472,P＞0.05;中滴度t=0.9045,P＞0.05;低滴度t=0.3536,P＞0.05).使用建立的方法测定MMRV疫苗中水痘病毒滴度,实测值与理论值之间的差异无统计学意义(t=1.7533,P ＞0.05).结论 建立了MMRV联合减毒活疫苗中水痘病毒滴度的测定方法.     

国产水痘减毒活疫苗质量分析

目的 对国产水痘减毒活疫苗进行质量分析，判断疫苗的安全性和有效性。方法 取2019年生产的102批水痘减毒活疫苗，进行鉴别试验、外观、pH值、渗透压摩尔浓度、水分、病毒滴定、热稳定性、牛血清白蛋白残留量、抗生素残留量、无菌、异常毒性、细菌内毒素含量的检查。结果 各项检查结果均符合《水痘减毒活疫苗制造与检定规程》和中国药典2015年版三部相关要求，病毒滴定和热稳定性试验结果均在3.4 lg噬斑形成单位/0.5 ml以上。结论  国产水痘减毒活疫苗是安全有效的。     

配制麻疹-腮腺炎-风疹-水痘联合减毒活疫苗的各病毒原液最适滴度研究

目的 研究配制麻疹-腮腺炎-风疹-水痘联合减毒活疫苗(measles-mumps-rubella-varicellacombined attenuated live vaccine,MMRV)的各病毒原液最适滴度.方法 将麻疹、腮腺炎、风疹和水痘病毒原液分别冻干,检测各冻干单价疫苗的滴度和热稳定性,观察病毒滴度的下降幅度.将4种病毒原液按不同配比配制MMRV,检测配制前后的各病毒滴度,摸索配制MMRV的最佳配比.按确认的最佳配比配制MMRV并冻干,检测冻干MMRV的各病毒滴度和热稳定性,确定配制MMRV的各病毒原液最适滴度.结果 各病毒原液冻干后,麻疹、腮腺炎、风疹和水痘病毒滴度分别下降约0.6、0.6、0.4 lgCCID50/ml和0.5 lgPFU/ml;各冻干单价疫苗37℃放置1周后,麻疹、腮腺炎、风疹和水痘病毒的滴度分别下降约0.6、0.5、0.5 lgCCID50/ml和0.5 lgPFU/ml.在配制MMRV过程中,仅腮腺炎病毒可能在一定程度上受到其他病毒的干扰.按确认的最佳配比配制的MMRV冻干后,麻疹、腮腺炎、风疹和水痘病毒滴度分别下降约0.5、0.6、0.5 lgCCID50/ml和0.6 lgPFU/ml;冻干MMRV于37℃放置1周后,麻疹、腮腺炎、风疹和水痘病毒滴度分别下降约0.6、0.6、0.5 lgCCID50/ml和0.5 lgPFU/ml.结论 在按确认的最佳配比配制MMRV时,麻疹、腮腺炎、风疹和水痘病毒原液的滴度需分别≥6.0、≥6.5、≥6.0 lgCCID50/ml和≥5.3 lgPFU/ml.     

流行性腮腺炎的预防

1967年以来,美国已经使用了腮腺炎减毒活疫苗(Jeryl Lynn 株)四千多万人份。无论单独使用或者与麻疹活疫苗和/或风疹疫苗联合使用,都产生满意的血清阳转率。临床反应轻微,保护作用可持续12年。美国现在对15月龄的男女儿童常规给以腮腺炎-麻疹-风疹疫苗接种。     

麻疹腮腺炎联合减毒活疫苗致不良反应

目的：探讨麻疹腮腺炎联合减毒活疫苗（MMR）致不良反应的情况,为临床疫苗的使用提供依据。方法：选择我县8～18个月龄常住健康人群900例,随机分为A、B、C三组各300例,其中,A组接种联合减毒活疫苗,B组接种麻疹疫苗,C组接种腮腺炎疫苗,观察三组对象的不良反应。结果：三组不良反应比较,A组发热率明显高于B组和C组,差异有统计学意义（P＜0.05）,其他不良反应的差异无统计学意义（P＞0.05）;同时,接种联合减毒活疫苗抗体阳转率同麻疹疫苗以及腮腺炎疫苗比较,差异无统计学意义（P＞0.05）。结论：联合减毒活疫苗有着目前临床使用的腮腺炎疫苗以及麻疹疫苗相同的安全性,具有重要的临床应用价值。     

某部队麻疹风疹联合减毒活疫苗应急接种效果及安全性评价

目的 观察麻疹风疹联合减毒活疫苗用于部队参加大型集聚性活动士兵的应急免疫接种效果及安全性. 方法 对2009年参加北京某大型演练活动士兵接种麻疹风疹联合减毒活疫苗,收集接种对象麻疹和风疹病史及疫苗接种史等资料,并与2008年参加北京某大型演练活动未接种疫苗士兵进行比较,分析该疫苗的保护效果及安全性. 结果 麻疹风疹联合减毒活疫苗应急接种对麻疹和风疹的保护率分别为98.51%和100.00%.疫苗的安全性较好,6475名接种者中发生全身反应8名,局部反应18名,经对症处理和休息后,均在48 h内基本恢复正常. 结论 麻疹风疹联合减毒活疫苗用于部队参加大型集聚性活动士兵的应急免疫接种,安全性好,可有效预防麻疹和风疹发生.     

12～18月龄健康儿童同时接种MM-RV和b型流感杆菌结合菌苗的安全性和免疫原性

作者比较了麻疹-腮腺炎-风疹-水痘疫苗(MMRV)和b型流感杆菌(Hib)结合菌苗(PedvaxHIB,每0.5ml含Hib多糖7.5μg,B群脑膜炎球菌外膜蛋白125μg)同时免疫与MMR加PedvaxHIB免疫后6周接种水痘减毒活疫苗的效果。     

水痘减毒活疫苗的渗透压分析

目的 建立水痘减毒活疫苗渗透压测定法.方法 冰点下降法.结果与结论 渗透压摩尔浓度的测定方法简单,重现性好,可作为水痘减毒活疫苗工艺稳定性考察的指标.     

Live attenuated measles, mumps, rubella, and varicella zoster virus vaccine (Priorix-Tetra)

The live attenuated tetravalent vaccine against measles, mumps, rubella, and varicella zoster viruses (MMRV) is a combination of the measles, mumps, and rubella (MMR) vaccine and the varicella zoster virus vaccine. The immunogenicity after each dose of a two-dose vaccination course of MMRV vaccine was generally similar to that of two doses of separately administered MMR plus varicella zoster vaccines, or a single dose of separately administered MMR plus varicella zoster vaccines followed by a dose of MMR vaccine, in infants aged 9-24 months. In infants aged 9-24 months administered a two-dose course of MMRV vaccine, geometric mean titers for antibodies against all vaccine antigens increased after the second dose relative to the first dose, with the increase being most pronounced for varicella zoster virus antibodies (10- to 21-fold). MMRV as the second vaccination was immunogenic in children aged 5-6 years who had previously received either MMRV or MMR as the first vaccination at 12-24 months of age. The immunogenicity for measles, mumps, rubella, and varicella zoster viruses, in terms of seropositivity and antibody titers, was not altered when MMRV was coadministered with a booster dose of diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b conjugate vaccine in infants aged 12-23 months. Nor was the immunogenicity of the latter vaccine altered by coadministration. The tolerability profile of MMRV vaccine was comparable to that of separately administered MMR plus varicella zoster vaccines or of MMR vaccine alone. Injection-site redness and fever (rectal temperature > or =38degreesC or axillary temperature > or =37.5degreesC) were the most frequent adverse events in both groups.     

A combination vaccine against measles, mumps, rubella and varicella

A new combination vaccine against measles, mumps, rubella and varicella (MMRV) from GlaxoSmithKline Biologicals has recently been approved in Europe. It combines the components from two well-established, live, attenuated vaccines against measles, mumps and rubella. This review presents a summary of the development of this MMRV vaccine from published clinical studies. Seroconversion rates and antibody titers after the first and second dose are similar to those observed after concomitant administration of the MMR and varicella vaccines. Furthermore, the clinical profile of this combination vaccine, in terms of injection- site and general tolerability, is similar to that of the component vaccines. A higher incidence of low-grade fever has been noted following the first dose of MMRV vaccine, although it is no different from component vaccines following the second dose. MMRV vaccines were recommended in Germany in 2006 for administration in two doses to children aged 11-14 months and 15-23 months. They offer a convenient way to implement varicella vaccination and to achieve high vaccine coverage rates mirroring those of MMR vaccines. For other countries considering introducing these vaccines, the advantages for children, parents and healthcare providers of protecting against four diseases in a single vaccine should be noted.     

麻疹、腮腺炎、风疹和水痘联合减毒活疫苗的研制

目的 建立麻疹、腮腺炎、风疹和水痘(measles,mumps,rubella and varicella,MMRV)联合减毒活疫苗的生产工艺和检定方法.方法 采用麻疹病毒沪-191株、腮腺炎病毒S79株、风疹病毒BRDⅡ株、水痘-带状疱疹病毒北京84-7株,在原代鸡胚细胞或人胚肺二倍体细胞2BS株中制备高滴度疫苗病毒原液.观察4种原液按不同比例稀释配制后病毒的滴度变化和相互干扰现象,确定MMRV疫苗中4种原液的配制比例,并筛选适宜保护剂,建立最佳冻干工艺.同时,建立MMRV联合减毒活疫苗的检定方法.采用t检验对结果进行比较.结果 选择最佳配制比例、保护剂和冻干工艺制备出连续多批MMRV疫苗,按国家药典要求检定全部合格.其中连续3批疫苗经国家检定机构检定合格:麻疹病毒基础滴度和37℃放置7d后的滴度分别≥3.9和≥3.5 lg半数细胞培养感染量(50％ cell culture infective dose,CCID50)/ml,腮腺炎病毒≥5.0和≥4.7 lgCCID50/ml,风疹病毒≥5.0和≥4.8 lgCCID50/ml,水痘病毒≥4.5和≥4.4 lg噬斑形成单位/ml.用建立的方法检测MMRV疫苗,结果4种病毒滴度实测值与理论值之间的差异无统计学意义(t值为0.149～1.838,P值均＞0.05).结论 建立了稳定、可行的MMRV疫苗生产工艺和检定方法.     

A new combination vaccine for measles, mumps, rubella and varicella

ProQuad is a recently approved combination vaccine for simultaneous vaccination against measles, mumps, rubella and varicella in children aged 12 months to 12 years. It combines two well-established vaccines: Measles, Mumps, Rubella Virus Vaccine Live (M-M-R II) and Varicella Virus Vaccine Live (Varivax with higher varicella-zoster titer). Whereas vaccination against measles, mumps and rubella has almost 100% coverage, vaccination against varicella shows a significantly lower uptake of approximately 84%. Clinical studies on the immunogenicity and efficacy of ProQuad demonstrated seroconversion rates and a magnitude of antibody response similar to those observed after administration of its individual components, M-M-R II and Varivax vaccines. The incidence of local side effects (pain/tenderness/soreness, erythema, swelling, ecchymosis and rash) and systemic adverse effects (fever, irritability, rash, upper respiratory infection, viral exanthema and diarrhea) is similar to or lower than that observed in component vaccines. ProQuad is a highly immunogenic combination vaccine with a good safety profile. The use of ProQuad combination vaccine will simplify immunization delivery by providing protection against more diseases with fewer injections and less pain, improve timely vaccination coverage and reduce the health-care costs for additional health visits. The ProQuad combination vaccine facilitates implementation of varicella vaccination into routine childhood immunization schedules and will help to protect children against these four potentially serious diseases.     

不同稳定剂配方的麻疹-腮腺炎-风疹-水痘联合减毒活疫苗的稳定性研究

目的 对比不同冻干稳定剂配方对麻疹-腮腺炎-风疹-水痘联合减毒活疫苗(measles,mumps,rubella and vericella combined live attenuated vaccine,MMRV)稳定性的影响,初步筛选出最佳配方。方法 对比2种含明胶（配方1、2）和1种无明胶冻干稳定剂配方（配方3）对MMRV在37、25及2～8 ℃保存后关键质量指标的影响。结果 37 ℃加速稳定性试验中,仅配方3产品4种病毒滴度均在合格范围内。25 ℃加速稳定性试验中,配方1产品1个月时腮腺炎和水痘病毒滴度即全部低于质量标准下限,配方2、3产品放置6个月,所有4种病毒滴度均在质量标准范围内,但配方2腮腺炎及水痘病毒滴度均处于标准下限。2~8 ℃长期稳定性试验中,配方1产品放置6个月,腮腺炎及水痘病毒滴度均低于质量标准下限,配方2、3产品的病毒滴度稳定性可分别保持18和24个月。结论 针对MMRV开发的无明胶冻干稳定剂配方3在冻干和保存过程中对4种病毒的活性保护效果最佳,其产品有效期至少为2年,并有进一步延长的潜力。研究结果也为日后研发降低明胶使用含量的麻疹系列疫苗冻干稳定剂配方提供了支持。     

Measles,mumps, rubella vaccine (Priorix; GSK-MMR): a review of its use in the prevention of measles,mumps and rubella

GSK-MMR (Priorix) is a trivalent live attenuated measles, mumps and rubella (MMR) vaccine which contains the Schwarz measles, the RIT 4385 mumps (derived from the Jeryl Lynn mumps strain) and the Wistar RA 27/3 rubella strains. GSK-MMR as a primary vaccination demonstrated high immunogenicity in clinical trials in >7500 infants aged 9-27 months, and was as immunogenic as Merck-MMR (MMR II). However, antimumps seroconversion rates and geometric mean titres (GMTs) were significantly higher in infants receiving GSK-MMR compared with Berna-MMR (Triviraten trade mark ) recipients. Coadministration of GSK-MMR with a varicella vaccine (Varilrix; GSK-MMR/V) did not significantly affect the immunogenicity of GSK-MMR. A persistent immune response to GSK-MMR has been demonstrated in follow-up data from several randomised trials. GMTs for measles, mumps and rubella antibodies remained high in GSK-MMR recipients 1-2 years post-vaccination and were similar to those in Merck-MMR recipients. The immunogenicity of GSK-MMR was high, and similar to that of Merck-MMR, when used as a second dose in children aged 4-6 or 11-12 years who had received a primary vaccination with Merck-MMR in their second year of life. Although there are no protective efficacy data concerning the GSK-MMR vaccine to date, the rubella Wistar RA 27/3 rubella and Schwarz measles strains have well established protective efficacy; the new RIT 4385 mumps strain is expected to afford similar protection from mumps to that achieved with mumps vaccines that contain the Jeryl Lynn mumps strain (e.g. Merck-MMR). GSK-MMR was well tolerated as a primary or secondary vaccination, and in most clinical studies comparing GSK-MMR with Merck-MMR as a primary vaccination in infants, GSK-MMR was associated with significantly fewer local adverse events (e.g. pain, swelling and redness). The incidence of local adverse events with GSK-MMR, GSK-MMR/V or Berna-MMR was similar. GSK-MMR and Merck-MMR were associated with similar rates of fever, rash and parotid gland swelling, but Berna-MMR was associated with a lower incidence of fever. In conclusion, GSK-MMR is a highly immunogenic MMR vaccine with good tolerability. In clinical trials, the immunogenicity of GSK-MMR was similar to that of Merck-MMR, and the mumps component was more effective at eliciting seroprotection than that of Berna-MMR. Furthermore, GSK-MMR causes fewer injection-site adverse events than Merck-MMR. As such, GSK-MMR is an attractive alternative for immunisation against measles, mumps and rubella.     

Immunizations and pregnancy: An update for pharmacists

ObjectiveTo review the safety of immunizations in pregnancy.Data sourcesPubMed search using the termsvaccine, immunizations, andpregnancy, as well as current national guidelines.Data synthesisImmunizations for women of childbearing age are an integral component of pregnancy planning. Some vaccines are compatible with pregnancy, whereas others, in particular live-attenuated vaccines, are contraindicated because of the theoretical risk to the fetus. The immunizing pharmacist must be aware of updated guidelines regarding the safe and appropriate use of vaccines during pregnancy. Certain routine adult vaccines are contraindicated during pregnancy, including the live-attenuated intranasal influenza, measles–mumps–rubella, varicella, zoster, and human papillomavirus vaccines. The trivalent inactivated influenza vaccine is specifically recommended for all women who are pregnant during influenza season. The hepatitis B, tetanus–diphtheria–acellular pertussis, and several other routine adult and travel vaccines may be administered safely in pregnancy if the patient meets certain risk criteria. Breast-feeding is compatible with all routine adult vaccines. Vaccinia (smallpox) and yellow fever vaccines are cautioned against use except in certain circumstances.ConclusionPharmacists can play an important role in recommending safe and appropriate vaccines before and during pregnancy.