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.     

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.     

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.     

器官移植受者接种麻疹、腮腺炎、风疹系列疫苗的有效性和安全性研究

器官移植受者术后易于感染许多疫苗可预防疾病,存在预后不良的风险,甚至可因严重感染而威胁生命。接种麻疹、腮腺炎、风疹（麻腮风）系列疫苗能有效降低器官移植受者术后的麻疹、腮腺炎和风疹发病率。此文综述了器官移植受者接种麻腮风系列疫苗的有效性和安全性,以期为器官移植受者制定个性化麻腮风系列疫苗免疫接种程序提供参考。     

MMR vaccine and idiopathic thrombocytopaenic purpura

AIMS: To estimate the relationship between idiopathic thrombocytopaenic purpura (ITP) and the measles, mumps and rubella (MMR) vaccination in children; calculating the relative risk estimate for ITP with in 6 weeks after MMR vaccination and the attributable risk of ITP within 6 weeks after MMR vaccination. METHODS: Using the General Practice Research Database we identified children with a first-time diagnosis of ITP from a base population of children aged less than 6 years between January 1988 and December 1999. After describing the characteristics of all the children identified with ITP, we focused on cases aged 13-24 months to perform a population-based, case-control analysis to estimate the relative risk of developing ITP within 6 weeks after MMR vaccination. We also calculated the risk of ITP attributable to the MMR vaccination. RESULTS: Sixty-three children with a first time diagnosis of ITP were identified; 23 cases were between 13 and 24 months old. The relative risk estimate for ITP within 6 weeks after MMR vaccination, compared to the combined group of unvaccinated children and children vaccinated with MMR more than 26 weeks previously was 6.3 (95% CI 1.3-30.1). The attributable risk of developing ITP within 6 weeks after MMR vaccination was estimated to be 1 in 25,000 vaccinations (95% confidence interval 21,300, 89,400). CONCLUSION: This study confirms the increased risk of ITP within 6 weeks after MMR vaccination. However, the attributable risk of ITP within 6 weeks after MMR vaccination is low.     

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.     

Computer assessment of alternative rubella vaccination strategies in New Zealand

Results from a dynamic computer model of rubella vaccination programmes indicate that consideration should be given to vaccinating all one-year-old girls and boys and revaccinating all girls at about 11 years of age, as well as continuing with the programme for susceptible women in the childbearing age group. With vaccine-induced immunity decaying at about 1% annually, the vaccination of 80 to 95% of all one-year-olds, 95% of 11 year old girls, and 5% of women aged 15 to 33 annually is expected to reduce congenital rubella syndrome deformities to less than 5% of the 1980 incidence by 1994, and to negligible levels thereafter. In comparison, continuation of the present scheme may reduce deformities to only 69% of 1980 levels by 1994 with a slow decline to 25% in 2010. (The 1980 levels used were computer generated to eliminate short-term fluctuations, and do not apply to actual figures from that year.) For convenience and better compliance, measles vaccine and the initial rubella vaccine may be given in combined form at 15 months without altering the effect of either. The rate of decay of immunity after vaccination is critically important in congenital rubella syndrome prediction, so that further accurate monitoring of immune status and congenital rubella incidence is essential.     

Optimum age for measles immunization in Romania

From 1979 to 1985 a serological survey was carried out to evaluate the opportunity to start measles vaccination at the age of 9 months. The following aspects were investigated: the persistence of maternal measles antibodies in 188 infants aged 1-8 months: such antibodies could not be detected over 7 months of age; the antibody response to measles vaccination in 181 infants vaccinated at the age of 9-11 months versus 291 children vaccinated when aged more than 12 months: no significant differences were found between the two groups; the age-specific persistence of vaccine-induced hemagglutination-inhibiting antibodies during the 1-4 years following vaccination: no significant difference was found in terms of the children's age upon vaccination. The results lend support to the recommendation to consider 9 months as a satisfactory age to initiate measles immunization in Romania.     

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.     

2000-2011年广西壮族自治区南丹县流行性腮腺炎流行病学特征分析

目的了解2000—2011年广西壮族自治区南丹县流行性腮腺炎的流行病学特征,为今后制订防治措施提供科学依据。方法收集广西壮族自治区南丹县2000—2011年报告的流行性腮腺炎病例资料,采用Excel软件进行分析。结果该县过去12年共发现流行性腮腺炎2 015例,年平均发病率为57.78/10万（2 015/3 487 563）,2010年发病率达到139.87/10万（436/311 715）,2 015例患者中95.88%（1 932/2 015）未进行麻疹、腮腺炎和风疹的联合疫苗（MMR）接种;全年每月均有腮腺炎病例出现,分为4—6月和10—12月即初夏和冬季2个高峰期,第1个高峰期是5月份,占总病例数的13.05%（263/2 015）,第2个高峰期是12月份,占总病例数的10.02%（202/2 015）;0-14岁占总病例数的84.22%（1697/2 015）,其中0-6岁占28.73%（579/2 015）,7-14岁占55.48%（1 118/2 015）;男女之比为1.63∶1;全县11个乡镇均有病例报道,其中以城关、六寨和吾隘镇3个镇的发病人数最多,占总病例的51.71%（1 042/2 015）,发病人数最低者为中堡乡,12年中发现腮腺炎病例仅21例。结论该县流行性腮腺炎年均发病率高于全区41.20/10万的平均水平,因此,近2年发病率明显上升,需进一步加强儿童MMR的接种及补种工作。     

Rubella vaccination: a study in adult male volunteers

One hundred adult male volunteers were randomized to receive either Merieux or Wellcome RA27/3 rubella vaccine. Prior to vaccination, 10% of the subjects were seronegative and all of these seroconverted. No significant boosting effect was found in those with a high pre-vaccine titre but some boost was shown in those with a low level. Side-effects reported were mild and self-limiting. No clinically or statistically significant difference could be found between the two vaccines. It is suggested that in view of the finding of 10% seronegative adult males it would be worthwhile considering routine screening of all medical staff who have contact with women in the early months of pregnancy.     

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。     

Varivax (Merck & Co)

Varivax is a live-attenuated varicella vaccine developed and launched in the US by Merck & Co for the treatment of chickenpox [413319]. The vaccine uses the Oka strain of the varicella virus licensed from the Biken Institute at Osaka University in Japan [178223]. By June 2001, Merck was also developing the vaccine for use in adults for herpes zoster infection [413319]. The FDA required post-marketing studies as a condition for its approval of Varivax, which was granted in March 1995 [174416]. The Centers for Disease Control & Prevention Advisory Committee on Immunization Practices recommended that Varivax should be administered at the same time as the measles, mumps and rubella vaccine. Unvaccinated children between the ages of 19 months and 13 years should be vaccinated by the time they are 13 years old [180148]. Varivax, from its launch in the spring of 1995 to the end of the third quarter 1995, produced sales of US $60 million [196542]. In June 2000, a second generation of Varivax, Varivax II, was launched for vaccination against chickenpox in individuals 12 months of age and older. Varivax II prevents the transmission of chickenpox with exactly the same safety and efficacy profile as Varivax; however, the new Varivax II has the advantage of being refrigerator-stable [371871].     

新兵接种麻腮风疫苗的免疫效果、影响因素及认知研究

目的:了解部队新兵接种麻腮风疫苗（MMR）的免疫效果、影响因素及对预防接种的态度。方法:采用整群抽样的方法选择驻广东某部2017年9月入伍的2个新兵营作为研究对象。选择新兵营一396人开展麻腮风联合减毒活疫苗免疫效果及影响因素研究,选择新兵营二473人开展疫苗的认知调查。对新兵接种MMR前后的抗体滴度进行检测,并开展问...     

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。     

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.     

342例儿童麻疹流行病学及临床分析

目的：探讨近年来麻疹的流行病学变化及临床特点。方法：采用描述法对我院收治的342例麻疹患儿进行回顾性分析。结果：麻疹的发病年龄趋向低龄化,3岁以下的婴幼儿为高发人群。不典型麻疹明显增多,农村发病人数高于城市,未预防接种者发病率高于已做预防接种者。结论：儿童麻疹发病率有上升的趋势,应加强麻疹监测力度,实施强化计划免疫策略是今后的工作方向。     

The changing age ecology of measles and its implications on measles control.

In the City of Gweru measles vaccination was commenced in 1971. With the advent of the Expanded Programme on Immunisation in 1981-82, measles vaccination coverage was increased, reaching over 80 pc in 1985 and after. Despite this vaccination effort measles morbidity rates have remained high and epidemics continue to occur periodically. It is argued that the shift of the disease from young age groups to older children, coupled with the fact that there are more vaccinees amongst cases with the disease, will mean that transmission will continue uninterrupted. Possible reasons for persistent transmission in older children are explored. It is concluded that measles revaccination is required to interrupt measles transmission.     

病毒性疫苗渗透压摩尔浓度的质量控制

目的  通过检测6种病毒性疫苗成品的渗透压摩尔浓度,比较不同疫苗检测均值的差异,并观察同种疫苗检测值的批间稳定性,为增加病毒性疫苗质量控制手段提供依据。方法  采用冰点下降法检测麻疹减毒活疫苗、风疹减毒活疫苗、麻疹腮腺炎联合减毒活疫苗、麻疹腮腺炎风疹联合减毒活疫苗、水痘减毒活疫苗、流感病毒裂解疫苗的渗透压摩尔浓度,对检测值进行统计学处理,计算变异系数。以麻疹腮腺炎风疹联合减毒活疫苗的渗透压摩尔浓度检测均值作为对照,进行方差齐性检验及假设检验,比较各疫苗检测均值的差异。结果  麻疹腮腺炎联合减毒活疫苗与对照相比,均值差异无统计学意义（t=1.66,P>0.05）;麻疹减毒活疫苗、风疹减毒活疫苗、水痘减毒活疫苗及流感病毒裂解疫苗与对照相比,均值差异均有统计学意义（Z>1.96,P<0.001）。同种疫苗批间渗透压摩尔浓度较为稳定,变异系数均<3%,变化幅度能控制在90%~110%均值范围内。结论  6种病毒性疫苗渗透压摩尔浓度存在一定差异,但同种疫苗检测值批间稳定性较好,因此,应根据不同疫苗的渗透压摩尔浓度,分别制定质量控制标准。     

Aseptic meningitis following mumps vaccine. A retrospective survey by the French Regional Pharmacovigilance centres and by Pasteur-Mérieux Sérums & Vaccins

Since 1989 many case series and observational studies of aseptic meningitis (AM) associated with the use of live attenuated mumps vaccines containing the Urabe AM9 strain have been reported worldwide. The aim of this retrospective reported AM in France following mumps vaccination with monovalent or multivalent vaccines containing the Urabe strain. Fifty-four cases of AM were reported to the Regional Pharmacovigilance centres or to the manufacturer from the time each vaccine was launched up until June 1992. Twenty cases were temporally associated with the administration of a monovalent mumps vaccine and 34 with a trivalent measles, mumps and rubella vaccine (MMR). A mumps virus was isolated in four cases in the cerebrospinal fluid and an Urabe-like strain was characterized twice by polymerase chain reaction (PCR). A probable mumps origin was assumed in 17 other cases where the patients presented with other clinical or biological signs of mumps infection. The clinical outcome of AM, known in 87% of the population, was always favourable. The global incidence of mumps vaccine-associated AM was 0.82/100,000 doses, which is significantly lower than the incidence in the unvaccinated population. Even considering that the actual incidence of AM is much higher when assessed by active surveillance studies, the risk/benefit ratio of mumps vaccine remains in favour of vaccination.