Studies on live rubella vaccine. V. Quantitative aspects of interference between rubella, measles and mumps viruses in their trivalent vaccine

Rubella vaccine combined with measles and mumps vaccines was administered in a single injection to children of 1 to 5 years of age. All three vaccines were serologically effective, and the clinical reactions caused by measles vaccine were considerably alleviated, when 6 x 10(3) PFU of rubella and 10(4) TCD50 per dose of mumps vaccines were combined with 5 x 10(4) TCD50 of measles vaccine. When a larger amount of mumps vaccine (3 x 10(5) TCD50/dose) was used, it caused interference with the rubella and measles viruses, i.e., the antibody response to rubella virus became poor and the incidence of clinical reactions to measles virus decreased. On the other hand, when 5 x 10(5) TCD50/dose of measles vaccine was combined with 10(4) TCD50/dose of mumps vaccine, the clinical reactions to measles virus were decreased but were almost the same as those induced by this vaccine alone.     

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.     

Joint and limb symptoms in children after immunisation with measles,mumps, and rubella vaccine.

OBJECTIVE--To assess whether the combined measles, mumps, and rubella vaccine increases the incidence of joint and limb symptoms in young children. DESIGN--Comparison of six week recalled incidence of symptoms in two groups of children: children who had been immunised at the start of the six weeks, and children eligible for immunisation but who had not received it. SETTING--South Manchester Health Authority. SUBJECTS--2658 children immunised during July 1989-February 1990 and 2359 not yet immunised. Questionnaires were returned for 1846 immunised children and 1075 not immunised. MAIN OUTCOME MEASURE--Recalled rate of joint and limb episodes determined by postal questionnaire and later by clinical follow up. RESULTS--Compared with non-immunised children the immunised group had an increased incidence of new episodes (relative risk 1.6 (95% confidence interval (1.2 to 2.1)) and first ever episodes, though this was not significant (1.7 (0.3 to 3.5)). The risk of first episodes was increased in girls (3.5 (1.1 to 12.2)) but not in boys (1.0 (0.4 to 2.6)). Similarly, an increased risk was seen in children aged under 5 (12.0 (1.6 to 92.3)) but not in older children (0.7 (0.3 to 1.5)). Most episodes were mild and self limiting, but three immunised children required hospital referral. CONCLUSION--Measles, mumps, and rubella vaccine is associated with an increased risk of episodes of joint and limb symptoms, especially in girls and children under 5. The risk of frank arthritis is substantially less than after wild rubella infection.     

Interference between strains in live virus vaccines, I: Combined vaccination with measles, mumps and rubella vaccine

One to four different lots of four commercially available trivalent measles-mumps-rubella vaccines were tested for their efficacy as measured by the induction of antibodies to the three vaccine viruses. All of the products were satisfactory although a 100% seroconversion rate was attained regularly only with rubella vaccine. The live virus in the different measles and mumps vaccine components and especially the relative amounts of measles to mumps virus varied widely. Obviously, the efficacy of a vaccine should not be judged only by the virus content. Of main importance is the further adjustment of the dosage of the interfering vaccine virus strains in relation to their attenuation.     

Factors affecting uptake of measles,mumps, and rubella immunisation.

OBJECTIVE--To study factors affecting uptake of measles, mumps, and rubella immunisation. DESIGN--Cohort study using data from computerised child health systems. SETTING--10 health districts in North East Thames and North West Thames regions. SUBJECTS--7841 children born in January to March 1990 and resident in the districts up till the end of October 1991. MAIN OUTCOME MEASURES--Overall uptake of measles, mumps, and rubella immunisation, variation of uptake among groups of children, and odds ratio of being vaccinated against measles, mumps, and rubella. RESULTS--The overall uptake rate of measles, mumps, and rubella immunisation for the study cohort in the 10 districts was 82%. Wide variation was identified among children with different demographic characteristics. Lower uptake was associated with absent or incomplete primary immunisation, including omission of pertussis vaccine. Other factors affecting uptake included the type of resident district, birth order, where registered for immunisation (general practitioner or clinic), and one parent family status. CONCLUSIONS--Many districts have difficulties in meeting the 90% target for measles, mumps, and rubella immunisation, mainly because of the characteristics of their local population. To increase overall coverage, the health service should target families with adverse factors, especially those whose children have missed previous immunisations.     

Surveillance of antibody to measles,mumps, and rubella by age.

Before the introduction of measles, mumps, and rubella vaccine a survey was carried out to measure antibody prevalence to the three viruses by age. A total of 8716 samples of serum collected by five public health laboratories in different parts of England during 1986-7 were tested. Despite the current measles vaccination programme 60% of children aged 1-2 years did not have measles antibody and over 80% did not have antibodies to mumps and rubella. In the 3-4 year age group 17% of the children were susceptible to measles, 55% to mumps, and 73% to rubella. The results suggest that vaccinating children early in the second year of life will be necessary to eliminate the three diseases. The survey provides baseline data for continuing surveillance of the immediate and long term effects of the new vaccination strategy.     

2',5'-Oligoadenylate synthetase and interferon in peripheral blood after rubella, measles, or mumps live virus vaccine

The temporal activation of the human interferon system by infection with virus was studied by serial measurements of both interferon in serum and activity of 2',5'-oligo adenylate synthetase in peripheral mononuclear leukocytes. A frequency distribution of baseline values of synthetase was established for normal individuals. Following subcutaneous inoculation of rubella vaccine virus, serum interferon rose briefly with a peak on Day 14. The peak concentration of synthetase also occurred on Day 14 but remained elevated for greater than 1 week. After measles virus, serum interferon did not rise above baseline, but synthetase peaked on Day 14 and remained elevated. Subcutaneous inoculation of mumps vaccine virus was associated with a brief period of elevation of the synthetase and no interferon in the serum. Thus, the determination of synthetase levels in tissue may be useful in some situations to reflect a small or transient elevation of endogenous interferon.     

Evaluation of live trivalent vaccine of measles AIK-C strain, mumps Hoshino strain and rubella Takahashi strain, by virus-specific interferon-gamma production and antibody response

A trivalent measles-mumps-rubella live virus vaccine, containing measles AIK-C strain, mumps Hoshino strain, and rubella Takahashi strain, was evaluated in 229 children, aged 1 to 5 years. The vaccine induced a high seroconversion rate: 221 (98.7%) out of 224 subjects initially seronegative for measles virus, 167 (93.3%) out of 179 initially seronegative for mumps virus, and 212 (99.1%) out of 214 initially seronegative for rubella virus. It also induced a sufficient cellular immunity against each of the three viruses in over 90% of the subjects, as judged by virus-specific interferon-gamma (IFN-gamma) production. Virus-specific IFN-gamma production was observed 10 days after vaccination by stimulation with measles virus and rubella virus and 14 days after vaccination by stimulation with mumps virus. Mumps-virus-specific IFN-gamma production was observed in 7 out of 12 recipients without seroconversion for mumps virus. And measles-virus-specific IFN-gamma production was demonstrated in one out of three recipients without seroconversion for measles virus. A significant correlation was observed between the serum antibody and IFN-gamma production six weeks after vaccination for measles virus (r = 0.201, P less than 0.01) and for mumps virus (r = 0.174, P less than 0.05) but not for rubella virus (r = -0.045, P less than 0.05). The incidence of febrile reactions of greater than or equal to 37.5 C was quite low, 14.4%, and that of greater than or equal to 39 C occurred in only 1.3% of the recipients. These results suggested that the trivalent vaccine induced sufficient humoral and cellular immunity and yet resulted in no more untoward reaction than observed from the measles vaccine alone.     

Potency estimation of measles, mumps and rubella trivalent vaccines with quantitative PCR infectivity assay.

The quantitative PCR infectivity assay is a combination of virus propagation and quantitative PCR. Previously [Schalk JAC, van den Elzen C, Ovelgonne H, Baas C, Jongen PMJM. Estimation of the number of infectious measles viruses in live virus vaccines using quantitative real-time PCR. J Virol Methods 2004;117:179-87.], we used this assay to estimate the titer of infectious measles virus in trivalent, live, measles, mumps, rubella vaccines (MMR). Here we describe the further improvement and development of the assay for simultaneous potency estimation of measles, mumps and rubella viruses. The potency of measles and mumps virus is estimated within one assay after 1 day of cell culture. The potency of rubella virus is estimated in a separate assay after 2 days of cell culture. Compared to conventional CCID50 and plaque assays, the quantitative PCR infectivity assay has the advantage in being fast because the assay is not dependent on the formation of cytopathic effect. Furthermore assay design is simplified: serological neutralization can be omitted because PCR is virus-specific and, under the conditions used, the individual components of trivalent measles, mumps, rubella vaccines do not interfere with each other. The assay was validated and compared to the performance of a plaque assay.     

Factors associated with uptake of measles,mumps, and rubella vaccine (MMR) and use of single antigen vaccines in a contemporary UK cohort: prospective cohort study

Objectives To estimate uptake of the combined measles, mumps, and rubella vaccine (MMR) and single antigen vaccines and explore factors associated with uptake and reasons for not using MMR.Design Nationally representative cohort study.Setting Children born in the UK, 2000-2.Participants 14 578 children for whom data on immunisation were available.Main outcome measures Immunisation status at 3 years defined as “immunised with MMR,” “immunised with at least one single antigen vaccine,” and “unimmunised.”Results 88.6% (13 013) were immunised with MMR and 5.2% (634) had received at least one single antigen vaccine. Children were more likely to be unimmunised if they lived in a household with other children (risk ratio 1.74, 95% confidence interval 1.35 to 2.25, for those living with three or more) or a lone parent (1.31, 1.07 to 1.60) or if their mother was under 20 (1.41, 1.08 to 1.85) or over 34 at cohort child’s birth (reaching 2.34, 1.20 to 3.23, for ≥40), more highly educated (1.41, 1.05 to 1.89, for a degree), not employed (1.43, 1.12 to 1.82), or self employed (1.71, 1.18 to 2.47). Use of single vaccines increased with household income (reaching 2.98, 2.05 to 4.32, for incomes of ≥£52 000 (€69 750, $102 190)), maternal age (reaching 3.04, 2.05 to 4.50, for ≥40), and education (reaching 3.15, 1.78 to 5.58, for a degree). Children were less likely to have received single vaccines if they lived with other children (reaching 0.14, 0.07 to 0.29, for three or more), had mothers who were Indian (0.50, 0.25 to 0.99), Pakistani or Bangladeshi (0.13, 0.04 to 0.39), or black (0.31, 0.14 to 0.64), or aged under 25 (reaching 0.14, 0.05 to 0.36, for 14-19). Nearly three quarters (74.4%, 1110) of parents who did not immunise with MMR made a “conscious decision” not to immunise. Conclusions Although MMR uptake in this cohort is high, a substantial proportion of children remain susceptible to avoidable infection, largely because parents consciously decide not to immunise. Social differentials in uptake could be used to inform targeted interventions to promote uptake.     

潍坊市健康人群麻疹、风疹、流行性腮腺炎抗体水平调查

目的了解潍坊市健康人群麻疹、风疹、流行性腮腺炎血清抗体水平,为消除麻疹、控制风疹及腮腺炎疫情提供依据。方法 2011年8月,采集昌乐、潍城2个县区<2、2～5、5～8、8～11、11～15、15～20、20～40、>40岁健康人群血标本,应用酶联免疫吸附试验检测麻疹、风疹、腮腺炎IgG抗体。结果检测总数320人,其中昌乐县健康人群的麻疹抗体阳性率为98.75%、潍城为96.25%;风疹抗体阳性率昌乐县健康人群为89.38%、潍城区为91.88%。昌乐、潍城两地区健康人群麻疹、风疹的抗体阳性率差异均无统计学意义(χ2=1.15、0.59,P>0.05);昌乐县健康人群腮腺炎抗体阳性率为84.38%、潍城区健康人群为66.25%,两者差异有统计学意义(χ2=14.14,P<0.01);8组不同年龄健康人群的麻疹抗体阳性率为92.50%～100%,风疹抗体阳性率为87.50%～92.50%,腮腺炎抗体阳性率为67.50%～85.00%,各年龄组间均无统计学意义(χ2=13.49、1.58、5.23,P>0.05)。结论潍坊市麻疹抗体阳性率较高,风疹、腮腺炎抗体阳性率相对偏低,今后须要积极开展学龄儿童麻腮风三联疫苗的查漏补种工作。