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.     

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.     

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.     

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。     

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。     

DTaP-IPV/Hib vaccine (Pentacel)

The combination vaccine diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated poliovirus and Haemophilus b conjugate (tetanus toxoid conjugate) vaccine (DTaP-IPV/Hib), which has been exclusively used in Canada for more than 10 years, is the first DTaP-based vaccine approved in the US that includes both poliovirus and Haemophilus influenzae type b (Hib) antigens. In clinical trials, the combined DTaP-IPV/Hib vaccine induced high immunogenecity against all of the vaccine antigens, including Hib. Administration of the DTaP-IPV/Hib vaccine as a four-dose series in infants provided high levels of seroprotection against diphtheria and tetanus toxoids, poliovirus types 1, 2, and 3, and Hib polyribosyl-ribitol-phosphate capsular polysaccharide conjugated to tetanus toxoid (PRP-T). Immune responses produced after doses 3 and 4 of DTaP-IPV/Hib vaccine were noninferior to those seen with separately administered DTaP, inactivated poliovirus, and Hib vaccines, apart from those against PRP-T in one study. Seroconversion rates for the five pertussis components in DTaP-IPV/Hib vaccine were noninferior to those seen in infants receiving the separately administered vaccines. A serology bridging study showed the noninferiority of four doses of DTaP-IPV/Hib vaccine to three doses of a DTaP vaccine in terms of seroconversion rates for filamentous hemagglutinin and fimbriae 2 and 3, but not pertactin. There were no clinically relevant changes in the immunogenicity of DTaP-IPV/Hib when coadministered with pneumococcal-7-valent-CRM197 vaccine or measles, mumps, and rubella vaccine and varicella zoster vaccine at 15 months. The tolerability profile of DTaP-IPV/Hib vaccine was generally similar to that of separately administered DTaP, IPV, and Hib vaccines.     

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.     

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.     

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。     

Swedish experience of two dose vaccination programme aiming at eliminating measles, mumps, and rubella.

In 1982 a two dose regimen was introduced in Sweden for the combined vaccination against measles, mumps, and rubella of children aged 18 months and 12 years. Since 1977 about half of the preschool children were vaccinated against measles annually, and since 1974 about 80% of 12 year old girls were vaccinated against rubella. During the period 1982 to 1985 90-93% of the eligible age cohorts of 18 month old children and 88-91% of the 12 year old children were immunised with the new combined vaccine. A study in 1982 of about 140 18 month old children who were nearly all seronegative before vaccination showed that 96%, 92%, and 99% seroconverted against measles, mumps, and rubella, respectively. A second study was carried out in 1983 of 247 12 year old children, of whom 11% lacked antibodies to measles, 27% to mumps, and 45% to rubella. This showed seroconversion in 82% and 80% against measles and mumps, respectively, and all children seroconverted against rubella. In the latest study in 1985 of 496 12 year olds 9% and 13% were seronegative against measles and mumps before vaccination, and 41% against rubella. Of these, 88% seroconverted to measles and 80% to mumps, and all converted to rubella when sera were tested by the haemolysis in gel method. After a neutralisation test against measles as well all children showed immunity to the disease. A low incidence of measles and declining figures for mumps and rubella were reported in 1984 to 1986. An outbreak of rubella during 1985 affected mainly boys in age cohorts in which only the girls had been vaccinated during the 1970s.     

早产儿疫苗免疫接种研究进展

目的：疫苗的免疫程序和疫苗使用指导原则是保证疫苗免疫效果的重要环节,也是《疫苗管理法》的重要内容之一。早产儿免疫系统发育不成熟,对于各种疫苗免疫反应低于足月儿。本综述为制定早产儿免疫程序提供参考。方法：本文对在早产儿中使用灭活脊髓灰质炎疫苗、百日咳-白喉-破伤风疫苗、乙型肝炎疫苗、肺炎链球菌疫苗、脑膜炎球菌结合疫苗和流感嗜血杆菌疫苗、轮状病毒疫苗、麻疹、腮腺炎、风疹和水痘疫苗等疫苗的免疫效果、安全性及耐受性研究进展进行了归纳整理。结果：本文对早产儿在接种不同疫苗、采取不同免疫策略时体液免疫和细胞免疫效果的研究进行了归纳总结,结果表明虽然早产儿的免疫功能相对较弱,但参照足月新生儿免疫方案接种疫苗后,大部分早产儿可以具有足够的免疫保护力。结论：本文为疫苗免疫程序的制定提供更全面的理解,为制定疫苗使用指导原则提供参考。     

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...     

国产麻腮风联合减毒活疫苗的稳定性观察

目的  观察国产麻腮风联合减毒活疫苗（麻腮风疫苗）的稳定性。方法  取24批上海生物制品研究所有限责任公司（上海公司）2008－2017年生产的麻腮风疫苗,按照国家食品药品监督管理局批准的麻腮风疫苗注册标准和中国药典的要求进行各项检定：在0个月进行热稳定性试验;在0和18个月进行鉴别试验,外观、水分、无菌、异常毒性检查,牛血清白蛋白残留量、抗生素残留量（2010年10月以后）、细菌内毒素（2013年12月以后）、pH值和渗透压摩尔浓度检测（2015年12月以后）;在0、6、12、18个月进行病毒滴定。同时对新、老车间生产的各3批疫苗进行加速稳定性与长期稳定性试验,重点考察水分和病毒滴度。结果  麻腮风疫苗在有效期内各项指标检定结果均符合注册标准和药典要求。质量可比性研究结果显示新老车间生产的疫苗质量相似。疫苗中水分都不高于3.0%,麻疹、腮腺炎、风疹病毒滴度分别为3.3～4.3 、4.6～5.6 、3.3～4.3 半数细胞培养感染量/ml。结论  上海公司10年间生产的麻腮风疫苗质量稳定、安全有效。     

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。     

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.     

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].     

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.     

Combined hepatitis A and B vaccines: a review of their immunogenicity and tolerability

Three combined hepatitis A and B vaccine preparations are commercially available in various countries: a two-dose paediatric formulation (Ambirix) [administered at months 0 and 6-12]; and a three-dose adult (Twinrix Adult) or paediatric (Twinrix Paediatric) formulation (administered at months 0, 1 and 6). The adult vaccine provides consistent, marked immunogenicity which is at least similar to that of its constituent vaccines used together and with a tolerability profile that is possibly improved. An accelerated, day-0, -7 and -21 regimen has also shown immunogenicity similar to that of the monovalent vaccines given concurrently, and now has an emerging role in adults likely to travel to hepatitis A virus (HAV) and/or hepatitis B virus (HBV) endemic regions within 1 month. The adult vaccine appears effective and generally well tolerated when given concurrently with monovalent typhoid vaccine (Typherix). Immunogenicity of the two-dose paediatric vaccine is high and appears to be similar whether administered as a month-0, -6 or month-0, -12 schedule and when compared to that of the three-dose paediatric vaccine (months 0, 1, 6), both of which provide a similar degree of protection to the adult vaccine. Although both preparations also provide high end-of-schedule seroprotection against hepatitis B surface antigen, protection between the first and second doses of the two-dose regimen appears lower than with the three-dose schedule. Therefore, the three-dose paediatric vaccine is a practical option in individuals at risk of immediate exposure to HBV, while the two-dose regimen may have an important function in immunisation programmes in regions where such risk is low. Combined hepatitis A and B vaccines are generally well tolerated. The most frequently reported adverse events in clinical trials were injection-site pain and redness, and general fatigue and headache; most events were mild and transient. Pharmacoeconomic models suggest the combined vaccine is cost effective compared with no vaccine (in children/adolescents) or monovalent hepatitis B vaccine (in children/adolescents and prison inmates). CONCLUSION: The three commercially available combined hepatitis A and B adult and paediatric vaccines are highly immunogenic and generally well tolerated; the adult vaccine demonstrates immunogenicity at least as marked as that of monovalent hepatitis A and B vaccines. While further research is required to confirm potential advantages such as improved cost effectiveness, the combined vaccines have established a key role in the prevention of hepatitis A and B in defined risk groups, and have an expanding role in population-based vaccination programmes with younger age groups.     

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.