国产麻疹流行性腮腺炎风疹联合疫苗初免效果及免疫程序探讨

目的为观察麻疹、流行性腮腺炎(腮腺炎)、风疹联合疫苗(MMR疫苗)的安全性和免疫原性,并探讨其免疫程序.方法选择91名8月龄儿童,接种MMR疫苗,观察接种后局部反应和全身反应,并检测接种后6周血清麻疹、腮腺炎、风疹抗体阳转率和几何平均滴度(GMT).结果91名8月龄儿童接种MMR疫苗后,有8名儿童发生一过性发热,2名儿童发生皮疹,2名儿童发生局部弱反应.麻疹、风疹、腮腺炎血凝抑制(HI)抗体阳转率分别为98.61%、100.00%、74.07%,GMT分别为145.25、1248.71、14.29.结论MMR疫苗对8月龄儿童接种具有较好的安全性和免疫原性,将其初免月龄定为8月龄儿童是可行的.     

冻干麻疹腮腺炎风疹联合减毒活疫苗安全性观察

目的 研究上海生物制品研究所的麻疹、腮腺炎、风疹三联联合减毒活疫苗(MMR)的安全性,为疫苗的使用提供科学依据.方法 分Ⅰ、Ⅱ、Ⅲ期进行,分别选择7～15岁、8～18月龄儿童接种沪MMR,同时设进口MMR疫苗、麻疹疫苗、腮腺炎疫苗、风疹疫苗作对照,进行安全性观察.结果 Ⅰ期7～15岁的11名接种沪MMR疫苗后,仅发生局部弱反应为27.3%;8～11月龄26名儿童接种沪MMR疫苗后,发热率和皮疹率分别为11.5%和15.4%,其中高热率为3.8%.Ⅱ、Ⅲ期观察1 188名8～18月龄儿童,沪MMR疫苗发热率为11.76%,皮疹率为3.64%,局部反应率为0.44%,其他反应率为0.33%.与对照疫苗比较,仅沪MMR疫苗发热率高于腮腺炎疫苗及风疹疫苗,差异有统计学意义,其他各反应差异均无统计学意义.结论 沪MMR疫苗具有与目前使用的麻疹疫苗、腮腺炎疫苗、风疹疫苗及进口MMR疫苗相同的免疫安全性.     

8月龄首剂接种国产麻疹腮腺炎风疹联合减毒活疫苗的安全性及免疫原性观察

目的观察国产麻疹腮腺炎风疹联合减毒活疫苗(MMR)对8月龄婴儿的安全性及免疫原性。方法选择8~9月龄未接种过麻疹、腮腺炎、风疹疫苗的健康儿童共77名,随机分别接种国产MMR疫苗40名和国产对照麻疹风疹减毒活疫苗(MR)37名,观察接种后的安全性及免疫原性。采用ELISA法检测血清中的麻疹、腮腺炎、风疹的IgG抗体水平。结果 77名观察对象全身反应率为6.49%,未观察到局部反应。2组疫苗免疫后麻疹抗体阳转率均为100%,MMR组腮腺炎抗体阳转率为87.50%,风疹抗体阳转率分别为82.50%和86.49%。2组疫苗免疫后麻疹抗体平均浓度分别为1714.63、和1 117.54IU/ml,抗体平均增长约627.72和12 870.35倍;MMR组腮腺炎抗体平均浓度为3 313.81U/ml,抗体平均增长分别约24.32倍;风疹抗体平均浓度分别为40.63和44.22IU/ml,抗体平均增长分别约40.63和44.22倍。2组间麻疹和风疹抗体阳转率、抗体平均浓度和平均增长倍数差异均无统计学意义(P0.05);麻疹、风疹抗体同时阳性率差异无统计学意义(P0.05)。结论 MMR疫苗对8月龄婴儿的安全性、免疫原性良好且能提供额外的腮腺炎抗体。     

不同厂家生产的冻干麻疹-风疹-腮腺炎三联减毒活疫苗免疫效果及安全性观察

目的 为了解不同厂家生产的冻干麻疹-风疹-腮腺炎三联减毒活疫苗免疫效果和安全性。方法 对545名18—24月龄儿童分组接种三种MMR疫苗，观察疫苗接种的安全性，并分别于免前免后采血，用微量血凝抑制法定量检测接种者的HI抗体GMT水平。结果三组观察对象接种MMR后麻疹HI抗体阳转率均在90％以上，风疹HI抗体阳转率均为100％，腮腺炎HI抗体阳转率均在80％左右，三组均无明显差异，疫苗接种后三组对象全身和局部反应轻微。结论国产与进口的三种MMR疫苗均有良好的有效性和安全性，可用于预防麻疹、风疹、腮腺炎。     

国产麻疹-腮腺炎-风疹联合疫苗与麻疹疫苗的免疫效果评价

目的研究探讨国产麻疹-腮腺炎-风疹联合疫苗(MMR)和麻疹疫苗的免疫效果差异性,为下一步更好使用联合疫苗提供依据。方法选择8月龄儿童随机分为两组,分别接种MMR疫苗和麻疹疫苗,于免前免后采血,用酶联免疫吸附法(ELISA)定量检测接种者相应的IgG抗体水平。结果观察对象接种MMR疫苗前后麻疹IgG抗体GMT分别为1.536、27.763,抗体阳转率85.71%;另一组观察对象接种麻疹疫苗前后麻疹IgG抗体GMT为1.205、30.867,抗体阳转率82.14%,两组相比差异无统计学意义。观察对象接种MMR疫苗后风疹IgG抗体和腮腺炎IgG抗体的阳转率都在80%以上。结论国产MMR疫苗具有良好的免疫原性。     

8月龄儿童接种麻疹-腮腺炎-风疹三联疫苗免疫效果及接种安全性观察

目的观察在8月龄儿童接种MMR的免疫效果和安全性，为在该年龄组用MMR替代麻疹单苗提供依据。方法选定部分合适对象开展MMR接种，在免前和免后6周分别采取外周静脉血1ml，分别作麻疹、风疹和腮腺炎的抗体滴度测定；同时对受种对象跟踪观察接种反应的发生情况。结果在8月龄儿童中开展MMR三联疫苗的接种在免疫效果上麻疹和风疹的免疫效果较好，免疫抗体阳转率分别为98．61％和100％，而其中的腮腺炎抗体阳转率和免疫成功率不高，仅分别为23．21％和31．25％。从接种的安全性来说，发生的局部反应轻微，也未出现严重的全身反应。结论在8月龄儿童开展MMR接种安全性较好，尚需提高MMR中的腮腺炎的免疫应答率。     

4~6岁儿童接种麻疹-流行性腮腺炎-风疹联合减毒活疫苗加强免疫的免疫原性与安全性研究

目的 探讨4~6岁儿童接种麻疹-流行性腮腺炎-风疹联合减毒活疫苗（MMR）后的加强免疫原性与安全性。方法 分别在山西省、内蒙古自治区以及北京市招募曾有8月龄和18月龄接种过1剂麻疹-风疹联合减毒活疫苗和MMR疫苗免疫史的4~6岁儿童作为研究对象,分为4、5、6岁组,进行MMR疫苗加强免疫研究。接种MMR疫苗前与接种后35~42 d各采集血标本3 ml。在研究期间,主动监测疫苗接种后30 min、1 d、2 d、3 d、4~12 d,以及13~42 d的不良事件。血清采用酶标法检测麻疹、流行性腮腺炎和风疹的IgG抗体。采用方差分析或非参数检验比较研究组间麻疹、腮腺炎和风疹抗体几何平均浓度（GMC）,采用χ²检验或Fisher确切概率法比较组间阳性率和不良事件发生率。结果 共500名完成免后采血儿童纳入免疫原性分析,535名儿童纳入安全性分析。总体不良事件发生率为20.37%,轻度不良事件最多。局部与全身不良事件发生率分别为0.37%和20.00%。局部不良事件的症状以接种部位发红为主,全身不良事件以发热症状为主,其次为咳嗽、皮疹、流涕等。在4~6岁进行1剂MMR疫苗加强免疫后,麻疹抗体、腮腺炎抗体与风疹抗体阳性率均在99%以上,3组间阳性率差异无统计学意义。3组间仅腮腺炎抗体GMC差异有统计学意义（P=0.042）,麻疹与风疹抗体相关结果均无差异。免前阴性者的麻疹、腮腺炎及风疹抗体GMC均低于免前阳性者。结论 在4~6岁儿童中进行MMR疫苗的加强免疫,具有良好的免疫原性与安全性,在4~6岁之间的加强免疫效果相近。     

冻干麻疹、腮腺炎、风疹三联减毒活疫苗免疫安全性观察

目的 观察北京天坛生物制品股份公司研制的冻干麻疹-腮腺炎-风疹三联减毒活疫苗的免疫安全性。方法 对接种MMR疫苗和接种麻疹疫苗、腮腺炎疫苗、风疹疫苗的8月龄以上儿童进行接种副反应观察。结果 156人接种MMR者仅5人发热，其中1人伴皮疹，未发现明显局部反应和异常反应，接种反应率仅3．2％。另3种单价苗319人次接种，发热24人次，其中5人次伴皮疹，接种反应率7．5％。结论 北京“天坛生物”的MMR具有很好的安全性。     

不同滴度麻疹腮腺炎风疹联合减毒活疫苗安全性观察

[目的]研究上海生物制品研究所的不同滴度麻疹、腮腺炎、风疹三联联合减毒活疫苗(MMR)的安全性,为疫苗的使用提供科学依据。[方法]分别选择8～15月龄儿童各300名接种高滴度沪MMR、低滴度沪MMR,同时选择8～15月龄儿童150名接种北京生物所MMR疫苗作对照,进行安全性观察。[结果]8～15儿童接种高滴度沪MMR疫苗、低滴度沪MMR疫苗、京MMR后,不良反应的发生率分别为17.33%、21.33%、17.33%。发热反应发生率分别依次为:15.33%,15.67%,14.67%。其中京MMR全部为中轻度发热反应,高滴度沪MMR接种后发生3例发热强反应,低滴度MMR接种后发生1例发热强反应。高、低滴度沪MMR与对照疫苗比较各项接种异常反应差异均无统计学意义。[结论]不同滴度沪MMR疫苗具有与目前使用MMR疫苗相同的免疫安全性。     

国产冻干麻疹-流行性腮腺炎-风疹联合减毒活疫苗免疫原性及安全性观察

目的观察国产冻干麻疹-流行性腮腺炎(腮腺炎)-风疹联合减毒活疫苗(MMR)的安全性及免疫原性。方法选取18~24月龄儿童210名,每名儿童接种1剂MMR,在接种后30min、6h、24h、48h、72h、7d、9d分别观察接种后临床反应,并于接种前、后6周各采集血清标本1份,用血凝抑制(HI)试验定量检测麻疹、腮腺炎、风疹IgG抗体。结果接种MMR后中、弱发热反应发生率4.29%,在1~2d内消退,无异常反应发生。免疫前麻疹HI抗体阴性儿童,免疫后抗体阳转率100%;免疫前麻疹HI抗体阳性儿童,免疫后抗体≥4倍增长率61.53%;抗体几何平均滴度(GMT)免疫后比免疫前增长3.8倍。免疫前腮腺炎HI抗体阴性儿童,免疫后抗体阳转率83.50%;免疫前腮腺炎HI抗体阳性儿童,免疫后抗体≥4倍增长率53.97%;抗体GMT免疫前1∶1.57,免疫后1∶3.52。免疫前风疹HI抗体均为阴性,免疫后抗体阳转率100%;抗体GMT 1∶487.2。免疫前、后麻疹、腮腺炎、风疹的抗体阳转率及GMT差异均有显著的统计学意义。结论国产冻干MMR具有良好的安全性和免疫原性。     

Immunogenicity of second dose measles-mumps-rubella (MMR) vaccine and implications for serosurveillance.

Measles and mumps, but not rubella, outbreaks have been reported amongst populations highly vaccinated with a single dose of measles-mumps-rubella (MMR) vaccine. Repeated experience has shown that a two-dose regime of measles vaccine is required to eliminate measles. This paper reports the effect of the first and second MMR doses on specific antibody levels in a variety of populations.2-4 years after receiving a first dose of MMR vaccine at age 12-18 months, it was found that a large proportion of pre-school children had measles (19.5%) and mumps (23.4%) IgG antibody below the putative level of protection. Only a small proportion (4.6%) had rubella antibody below the putative protective level. A total of 41% had negative or equivocal levels to one or more antigens. The proportion measles antibody negative (but not rubella or mumps) was significantly higher in children vaccinated at 12 months of age than at 13-17 months. There was no evidence for correlation of seropositivity to each antigen, other than that produced by a small excess of children (1%) negative to all three antigens. After a second dose of MMR, the proportion negative to one or more antigens dropped to <4%. Examination of national serosurveillance data, found that following an MR vaccine campaign in cohorts that previously received MMR, both measles and rubella antibody levels were initially boosted but declined to pre-vaccination levels within 3 years.Our study supports the policy of administering a second dose of MMR vaccine to all children. However, continued monitoring of long-term population protection will be required and this study suggests that in highly vaccinated populations, total measles (and rubella) IgG antibody levels may not be an accurate reflection of protection. Further studies including qualitative measures, such as avidity, in different populations are merited and may contribute to the understanding of MMR population protection.     

An evaluation of measles, mumps and rubella vaccine in a population of Yorkshire infants

In October 1988 combined measles, mumps and rubella (MMR) vaccination replaced monocomponent measles as part of the routine childhood vaccination programme in the United Kingdom. Prior to this policy change a study was undertaken in 335 children aged 15 months, to evaluate the clinical reactions and immunogenicity of the new combined MMR vaccine (Trimovax, Immravax, Merieux), in comparison with an established monocomponent measles vaccine (Rouvax, Merieux). Parents were asked to select whether their child should receive MMR vaccine or measles monocomponent; over 95% chose MMR. Children who were given the MMR vaccine had seroconversion rates of 96% for measles, 97% for mumps and 100% for rubella, whilst those who received monocomponent measles vaccine had a seroconversion rate of 100%. The number of side effects reported was similar with both vaccines; all were mild and self-limiting. The results from this study confirm the efficacy and low reactogenicity of MMR vaccine and support its use as part of the routine childhood immunisation programme in the United Kingdom.     

The immunogenicity and reactogenicity of the trivalent vaccine, Trimovax, indicated for prevention of measles, mumps, and rubella, in 12-month-old children in Belarus

In the Republic of Belarus, immunization of children against measles and mumps had been carried out using monovalent preparations according to the national schedule of measles vaccination at 12 months of age and mumps vaccination at 24 months of age. A rise of rubella incidence in the last few years (i.e., for the official registration period 1980 to 1998, there was an increase from 72.2 to 607.5 cases per 100,000 population) made it necessary to implement immunization against this infection, as well. Therefore, in 1996, combined vaccination against measles, mumps, and rubella of 12-month-old children was carried out for the first time in a clinical trial that used the vaccine Trimovax [Aventis Pasteur (formerly, Pasteur Mérieux Connaught), Lyon, France]. The reactogenicity of the vaccine was investigated in 372 children. Post-vaccination reactions were noted in 5.6% of children; in 1.3% of children the reactions were classified as severe [i.e. associated with body (axillary) temperature > or = 38.6 degrees C]. For the evaluation of immunogenicity, sera from 324 children were obtained 2 to 2.5 months after inoculation, and serum antibody levels were measured by enzyme immunoassays. Among the vaccines, protective antibody titers (expressed in inverse of dilution units) were observed to measles (> or = 1:50) in 97.8%, to mumps (> or = 1:50) in 93.8%, and to rubella (> or = 1:100) in 96.0% of children. Antibodies to all three components of the vaccine were mainly present in intermediate (1:200-1:800) or high (> or = 1:1600) titers: to measles in 96.3%; to mumps in 75.8%; and to rubella in 73.5% of vaccines. The results of these trials are evidence of the good safety and immunogenicity of this MMR vaccine, which provides an alternative to the currently used measles and mumps monovaccines, with the additional benefit of providing immunity against rubella, as well.     

Safety and immunogenicity of a measles–mumps–rubella–varicella vaccine given as a second dose in children up to six years of age

Two doses of measles–mumps–rubella vaccine (MMR) are widely recommended and consideration is being given to a similar schedule for varicella vaccine. A combined measles–mumps–rubella–varicella vaccine (MMRV) could be considered for this second dose in children previously vaccinated separately with MMR and varicella vaccines. Healthy children (N = 390) aged 15–75 months (median 54 months) previously immunized with MMR and varicella vaccines were randomly allocated to receive MMRV or separate injections of MMR and varicella vaccines. Before administration of study vaccines, seropositivity rates were 96.4% for measles, 94.3% for mumps, 99.5% for rubella, and 97.9% for varicella. Post-immunization, seropositivity rates were 99.5% for measles and mumps and 100% for rubella and varicella in the MMR + varicella group and 100% for all four antigens in the MMRV group; a 26.2- and 27.2-fold increase in varicella titer was observed in the MMR + varicella vaccine and MMRV groups, respectively. Except for more frequent pain in the MMRV group (33.3% vs. 23.7%, p = 0.043), there were no differences in the incidence of local and solicited symptoms between groups. In children primed with MMR and varicella vaccine, MMRV had non-inferior immunogenicity and similar safety profiles as a second dose of licensed MMR and varicella vaccine administered concomitantly.     

Duration of the immune response to MMR vaccine in children of two age-different groups

A combined vaccine against measles, mumps and rubella (MMR) was administered to both a group of children aged 10–12 months simultaneously with booster doses of compulsory diphtheriatetanus toxoids and oral poliovirus vaccine and a group of children aged 15–24 months who had previously received booster doses of the compulsory vaccines.Apart from one subject belonging to the second group who was non responder and one from the same group who did not seroconvert against the mumps virus alone, 5 to 6 weeks after MMR vaccine administration we found protective levels of antibodies against measles, mumps and rubella viruses in all children. The follow up of both groups at 3 years did not reveal difference between the two groups. Protective levels of serum antibodies against measles and mumps were found in the two groups, altough a significant decline of rubella antibodies was shown (p < 0.05).Since the immunogenicity of the vaccines in the two groups did not differ, we recommend that the scientific community reconsider the vaccination schedule until now recommended. In our opinion the MMR vaccine should be administered simultaneously with booster doses of diphtheria-tetanus toxoids and oral poliovirus vaccine at 10–12 months of age because this policy improves parents' compliance, markedly reduces community costs and simplifies routine immunization schedule.     

Changes of the immunological patterns against measles, mumps and rubella. A vaccination programme studied 3 to 7 years after the introduction of a two-dose schedule

A two-dose vaccination programme using a combined measles, mumps and rubella vaccine (MMR) and administration at the ages of 18 months and 12 years was introduced in 1982. The 12-year-old schoolchildren were tested yearly from 1985 to 1989 on serum samples obtained prior to and after vaccination. Each year between 420 and 756 children were tested. The method used for antibody testing was the haemolysis-in-gel (HIG) assay. For measles also the enzyme-linked immunosorbent assay (ELISA) and the neutralization titre (NT) were applied. Only minor variations of the prevaccination immunity to measles were seen during the period 3-7 years after introduction of the programme. The age groups studied had partly been vaccinated against measles earlier. Between 12 and 16% lacked prevaccination immunity. In contrast the immunity to mumps and rubella of the 12-year-old children decreased considerably during the study period. No general vaccination against these diseases had been performed. Thus the susceptibility to mumps increased from 14% in 1985 to 39% in 1989 and to rubella from 41 to 57%. The seroconversion rate of children seronegative for measles was high, i.e. 100% in 1985 and later varied between 96 and 97%. For mumps, the seroconversion rate was lower and varied between 72 and 88%. All sera converted to rubella. During the follow-up period there was a declining incidence of measles, mumps and rubella. The relationship between the vaccination and reduction of disease and natural immunity strongly suggests that the association is causal and that this vaccination policy reduced the transmission of infection.     

麻疹-流行性腮腺炎-风疹联合减毒活疫苗流行性腮腺炎组份免疫效果观察

目的对麻疹-流行性腮腺炎（流腮）-风疹联合减毒活疫苗（Measles,Mumps and Rubella Combined Atteruated Live Vaccine,MMR）中,流腮组份的免疫效果进行观察评价。方法对接种MMR后,流腮组份免疫学效果进行分析评价,并追踪观察记录2年内受种人群及本地人群中流腮发病情况。结果接种MMR前,流腮抗体几何平均滴度（Geometric Mean Titer,GMT）为1∶6.87,免疫后GMT为1∶26.35,免疫后GMT是免疫前GMT的3.8倍,免疫前、后GMT差异有统计学意义（Z=-6.22,P〈0.001）。免疫前、后流腮抗体阳性率分别为64.63%、95.12%,差异有统计学意义（χ2=23.71,P〈0.001）。免疫前、后流腮抗体阴性者与阳性者GMT和免疫前相比差异均有统计学意义（Z=-4.40,P〈0.001;Z=-4.84,P〈0.001）。免疫前流腮抗体阴性者与阳性者接种MMR后,免疫成功率分别为86.21%、54.72%,差异有统计学意义（χ2=8.266,P=0.004）。对受种人群及本地人群进行为期2年的流腮发病追踪观察,在受种人群中未发现流腮病例报告。结论在3-6岁儿童中接种MMR,对于预防流腮效果良好,产生的保护效果至少能维持2年。