Adverse events following a third dose of measles,mumps, and rubella vaccine in a mumps outbreak

During a 2009–2010 mumps outbreak in a New York State village, a third dose of measles, mumps, and rubella (MMR) vaccine was administered to children in three schools as a control measure. Information on local and systemic adverse events (AE) was collected by a self-report survey distributed to all children in grades 6–12. A comprehensive search for AE following MMR vaccination was conducted using physician records and the Vaccine Adverse Events Reporting System (VAERS). A literature search was performed for published reports pertaining to AE associated with mumps-containing vaccine, using the Jeryl-Lynn strain, from 1969 to 2011. A total of 1755 individuals received the third dose; 1597 (91.0%) returned the survey. Of those, 115 (7.2%) reported at least one local or systemic AE in the 2 weeks following vaccination. The most commonly reported AE were “pain, redness, or swelling at the injection site” (3.6%) and “joint or muscle aches” (1.8%). No serious AE were reported in the survey, physician records or through VAERS. The proportions of AE found in the present study were lower than or within the range of those reported in prior studies of first- and second-dose MMR vaccine studies. The results of this study suggest that a third dose of MMR vaccine administered in an outbreak setting is safe, with injection site reactions reported more frequently than systemic reactions. However, to assess risk for rare or serious AE after a third dose of MMR vaccine, longer term studies would be required.     

Ethnicity as a correlate of the uptake of the first dose of mumps, measles and rubella vaccine

The aim of this study was to investigate whether a relationship exists between ethnicity and uptake of the first dose of mumps, measles and rubella (MMR1) vaccination, and to study important factors influencing the parental decision about vaccination. Examination of routine data on uptake of MMR1 vaccine among children living in the London borough of Brent, North West London, for associations with ethnicity was carried out. Six focus group interviews were held and a questionnaire on factors related to immunisation by convenience samples of mothers from Asian, Afro-Caribbean and White backgrounds was completed. The routine data reported MMR1 vaccine status for 6444 children living in Brent who were aged between 18 months and 3 years on 1 December 2003. A total of 37 mothers took part in the 6 focus group sessions. Significantly higher coverage by MMR1 vaccine in the Asian population (87.1%) compared with Afro-Caribbeans (74.7%) and the White group (57.5%) was noticed. The qualitative data revealed clear differences between the ethnic groups with respect to awareness of the controversy surrounding MMR vaccination (related to use of English-language media) and influence of grandparents and health professionals in decisions about immunisation. A multiple logistic regression model showed that although coverage of MMR vaccination increased with increasing socioeconomic status, there was no evidence of a statistically significant interaction between socioeconomic status and ethnicity. An important association between ethnicity and uptake of MMR1 vaccine is observed. This has implications for efforts to improve the currently inadequate levels of MMR vaccination across the population as a whole.     

麻疹-腮腺炎-风疹-水痘四联疫苗的研究现状

麻疹-腮腺炎-风疹-水痘(MMRV)联合疫苗自21世纪初上市以来,已应用十余年,显示出良好的免疫原性,不良反应小.MMRV疫苗的引进及应用,或有助于提高接种人群的依从性,从而有效控制相关疾病的发生.本文对MMRV疫苗的现状进行综述,以期为相关机构制定免疫策略提供参考.     

Influenza vaccine concurrently administered with a combination measles,mumps, and rubella vaccine to young children

Children aged 11 to <24 months received 2 intranasal doses of live attenuated influenza vaccine (LAIV) or placebo, 35 ± 7 days apart. Dose 1 was administered concomitantly with a combined measles, mumps, and rubella vaccine (Priorix). Seroresponses to measles and mumps were similar between groups. Compared with placebo, response rates to rubella in LAIV + Priorix recipients were statistically lower at a 15 IU/mL threshold (83.9% vs 78.0%) and the prespecified noninferiority criteria were not met. In a post hoc analysis using an alternate widely accepted threshold of 10 IU/mL, the noninferiority criteria were met (93.4% vs 89.8%). Concomitant administration with Priorix did not affect the overall influenza protection rate of LAIV (78.4% and 63.8% against antigenically similar influenza strains and any strain, respectively).     

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.     

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3...     

Mutual interference on the immune response to yellow fever vaccine and a combined vaccine against measles, mumps and rubella

A randomized trial was conducted to assess the immunogenicity and reactogenicity of yellow fever vaccines (YFV) given either simultaneously in separate injections, or 30 days or more after a combined measles-mumps-rubella (MMR) vaccine. Volunteers were also randomized to YFV produced from 17DD and WHO-17D-213 substrains. The study group comprised 1769 healthy 12-month-old children brought to health care centers in Brasilia for routine vaccination. The reactogenicity was of the type and frequency expected for the vaccines and no severe adverse event was associated to either vaccine. Seroconversion and seropositivity 30 days or more after vaccination against yellow fever was similar across groups defined by YFV substrain. Subjects injected YFV and MMR simultaneously had lower seroconversion rates - 90% for rubella, 70% for yellow fever and 61% for mumps - compared with those vaccinated 30 days apart - 97% for rubella, 87% for yellow fever and 71% for mumps. Seroconversion rates for measles were higher than 98% in both comparison groups. Geometric mean titers for rubella and for yellow fever were approximately three times higher among those who got the vaccines 30 days apart. For measles and mumps antibodies GMTs were similar across groups. MMR's interference in immune response of YFV and YFV's interference in immune response of rubella and mumps components of MMR had never been reported before but are consistent with previous observations from other live vaccines. These results may affect the recommendations regarding primary vaccination with yellow fever vaccine and MMR.     

Measles,mumps, and rubella antibody patterns of persistence and rate of decline following the second dose of the MMR vaccine

BackgroundAntibodies to measles, mumps, and rubella decline 3% per year on average, and have a high degree of individual variation. Yet, individual variations and differences across antigens are not well understood. To better understand potential implications on individual and population susceptibility, we reanalyzed longitudinal data to identify patterns of seropositivity and persistence.MethodsChildren vaccinated with the second dose of measles, mumps, rubella vaccine (MMR2) at 4–6 years of age were followed up to 12 years post-vaccination. The rates of antibody decline were assessed using regression models, accounting for differences between and within subjects.ResultsMost of the 302 participants were seropositive throughout follow-up (96% measles, 88% mumps, 79% rubella). The rate of antibody decline was associated with MMR2 response and baseline titer for measles and age at first dose of MMR (MMR1) for rubella. No demographic or clinical factors were associated with mumps rate of decline. One month post-MMR2, geometric mean titer (GMT) to measles was high (3892 mIU/mL), but declined on average 9.7% per year among those with the same baseline titer and <2-fold increase post-MMR2. Subjects with ≥2-fold experienced a slower decline (≤7.4%). GMT to rubella was 149 one month post-MMR2, declining 2.6% and 5.9% per year among those who received MMR1 at 12–15 months and >15 months, respectively. GMT to mumps one month post-MMR2 was 151, declining 9.2% per year. Only 14% of subjects had the same persistence trends for all antigens.ConclusionsThe rate of antibody decay varied substantially among individuals and the 3 antigen groups. A fast rate of decline coupled with high variation was observed for mumps, yet no predictors were identified. Future research should focus on better understanding waning titers to mumps and its impacts on community protection and individual susceptibility, in light of recent outbreaks in vaccinated populations.     

Epidemiology of measles,mumps and rubella in Italy

A serosurvey for measles, mumps and rubella was conducted in Italy; incidence based on statutory notifications over the last three decades was also calculated. In Italy the diseases followed an endemic-epidemic pattern, with an incidence peak every 2-4 years, and had a limited reduction of incidence attributable to childhood immunization. Lower notification rates were observed in the Southern regions. This is possibly related to greater under notification in the South and is confirmed by our seroprevalence data. Incidence of measles and rubella and proportion of cases among young adults increased significantly in the three decades considered, but not for mumps. Serological data confirmed that these infections are still very frequent in Italy, without significant geographic variation in the country. In the age groups 2-4 and 5-9 years the percentage of individuals still susceptible to each virus was higher than 30%. The proportion of susceptible subjects older than 15 years was similar for the three infections (6.1, 11.7 and 8.8% for measles, mumps and rubella, respectively). The low vaccine coverage for rubella and measles in Italy has so far only partially affected the occurrence of the diseases. No impact of mumps vaccination is visible. The average number of deaths, for each disease, has decreased during the three study periods. Today the priority in Italy is to halt the progressive increase of the mean age of acquisition of the three infections, to eliminate differences in coverage among regions and to conform to European standards. This will be achieved through a combination of increasing MMR vaccine coverage before 2 years of age, implementing vaccination campaigns for low seroprevalence age groups, and/or introducing a second dose of MMR, depending on the level of current MMR coverage.     

Effect of jet injection on infectivity of measles,mumps, and rubella vaccine in a bench model

Disposable-syringe jet injectors (DSJIs) with single-use, auto disable, needle-free syringes offer the opportunity to avoid hazards associated with injection using a needle and syringe. Clinical studies have evaluated DSJIs for vaccine delivery, but most studies have focused on inactivated, subunit, or DNA vaccines. Questions have been raised about possible damage to live attenuated viral vaccines by forces generated during the jet injection process. This study examines the effect of jet injection on the integrity of measles, mumps, and rubella vaccine (MMR), measured by viral RNA content and infectivity. Three models of DSJIs were evaluated, each generating a different ejection force. Following jet injection, the RNA content for each of the vaccine components was measured using RT-qPCR immediately after injection and following passage in Vero cells. Jet injection was performed with and without pig skin as a simulation of human skin. There was little to no reduction of RNA content immediately following jet injection with any of the three DSJIs. Samples passaged in Vero cells showed no loss in infectivity of the measles vaccine following jet injection. Mumps vaccine consistently showed increased replication following jet injection. Rubella vaccine showed no loss after jet injection alone but some infectivity loss following injection through pig skin with two of the devices. Overall, these data demonstrated that forces exerted on a live attenuated MMR vaccine did not compromise vaccine infectivity. The bench model and protocol used in this study can be applied to evaluate the impact of jet injection on other live virus vaccines.     

Targeted mailing of information to improve uptake of measles, mumps, and rubella vaccine: a randomised controlled trial

Uptake of the measles, mumps, and rubella vaccine in the United Kingdom has declined to levels that will allow outbreaks of these preventable diseases to occur. A leaflet sent with a personalized reminder did not increase vaccine uptake in children who had not been immunised at 21 months of age.     

Vaccine-induced measles virus antibodies after two doses of combined measles, mumps and rubella vaccine: a 12-year follow-up in two cohorts

In Finland, a two-dose vaccination programme against measles, mumps and rubella (MMR) was begun in 1982. The programme with high coverage (97–98%) has eliminated these three diseases from Finland. The aim of the present study was to follow up the kinetics of measles virus antibodies in MMR vaccinated cohorts. We have followed the kinetics of measles virus antibody levels induced by vaccination in the same individuals immunized with their first MMR vaccine in 1982. After 12 years 80% of the original children remained available for sampling. Antibodies to measles virus were measured by haemagglutination inhibition (HI) and plaque reduction neutralization (NT) techniques. The primary dose induced 99.4% seroconversion for measles with a geometric mean HI antibody titre (GMT) of 1/269 (±219), equivalent to 4304 mIU (milli-International Units) ml⁻¹ in group A. The 12-year follow-up specimens showed a measles seropositivity rate of 100% as assayed with the HI and NT tests with a mean HI antibody titre of 1/39 (±54), equivalent to 624 mIU ml⁻¹. The vaccination-induced measles virus antibodies decline in the absence of natural booster infections. It is important to follow how long the protection achieved by the present vaccine programme will last after elimination of indigenous measles.     

Seroprevalence of measles, mumps and rubella antibodies in Luxembourg: results from a national cross-sectional study

A serological prevalence survey was carried out in Luxembourg during 2000-2001 to determine the antibody status of the Luxembourg population against vaccine-preventable infections. Blood samples of children and adolescents were collected prospectively in randomly selected schools. Samples of adults were obtained through volunteer patients of the national health laboratory or of the mandatory pre-nuptial test. Measles, mumps and rubella (MMR) virus antibody concentrations were measured using commercial ELISA tests. Age-standardized prevalence of measles, mumps and rubella virus antibodies was found to be 96.58, 75.40 and 95.69% respectively. Significant age-dependence of serology was observed for all three infections, with study participants born after the introduction of the MMR vaccine experiencing a gradual decline of antibodies following vaccination in childhood. Older study participants who were more likely to have antibodies from natural infection had consistently higher titres than younger individuals. Present vaccination coverage with MMR appears to be sufficient to prevent large local outbreaks of measles and rubella, but probably not mumps.     

Modelling forces of infection for measles, mumps and rubella

Serological data from 8870 persons collected prior to the introduction of measles, mumps and rubella (MMR) vaccine in the UK are used to describe the rate at which individuals acquire infection by these diseases at different ages. A parsimonious model is developed and fitted under various interpretations of the data, particularly concerning the probability of lifelong susceptibility to infection. It is shown that, while the force of infection curves are relatively robust in their general features, they exhibit considerable sensitivity in matters of important detail. This is true in particular of the values taken by the force of infection in older age groups. As a result, estimates of the average age at infection are highly sensitive to these interpretations. This in turn may limit the accuracy of predictions from mathematical models based on these parameters, in particular regarding the level of immunization required for eradication of disease.     

Clinical safety issues of measles, mumps and rubella vaccines

The clinical safety of measles and measles-mumps-rubella vaccines has been questioned in recent reports that propose a possible link between measles virus or measles vaccines and the occurrence of juvenile Crohn disease and autism. This article reviews the outcomes of several laboratory investigations which were carried out independently to identify the presence or absence of measles virus in the intestinal tissues derived from cases of inflammatory bowel disease. One research group reported the presence of measles virus particles and genomic RNA in inflammatory bowel disease tissues, but this could not be confirmed by other groups, despite use of techniques that are highly specific and sensitive for the detection of measles virus nucleic acid in clinical specimens down to the molecular level. Based on the published data reviewed here, it can be concluded that there is no direct association between measles virus or measles vaccines and the development of Crohn disease, a conclusion which is supported by most epidemiological findings.     

Immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine administered concomitantly with measles, mumps, rubella, varicella vaccine in healthy toddlers

Background

Invasive meningococcal disease can have devastating outcomes, especially in high-risk groups such as infants. As infants are recommended to receive multiple vaccines during a single office visit, this phase 3 study assessed the safety and immune response to MenACWY-CRM at alternative visits in older infants and concomitant use with measles, mumps, rubella, varicella vaccine (MMRV) at 12 months of age.

Methods

Two age groups were concurrently enrolled: 7- to 9-month-old infants who received 2 doses of MenACWY-CRM at 7–9 and 12 months and were randomized 1:1 to receive MenACWY-CRM with or without MMRV at 12 months, and 12-month-old infants who received MMRV only at12 months. Using predefined non-inferiority criteria, immune responses to the antigens in MMRV were compared between those who did and did not receive MenACWY-CRM; immune responses to MenACWY-CRM as measured by the percentage of subjects with human serum bactericidal activity (hSBA) titers ≥ 8, were compared between those who did and did not receive concomitant MMRV. Adequacy of the immune response to 2 doses of MenACWY-CRM administered at 7–9 and 12 months was also assessed. Local and systemic reactions, adverse events resulting in withdrawal or requiring medical attention and serious adverse events were monitored.

Results

Concomitant administration of MMRV with MenACWY-CRM did not affect the immune response to either vaccine. The 2-dose series of MenACWY-CRM induced adequate immune response to all 4 serogroups. No increased reactogenicity was observed with MenACWY-CRM + MMRV compared with MMRV alone, and there were no study-related serious adverse events.

Conclusions

Concomitant administration of MenACWY-CRM with MMRV vaccinations at 12 months was well-tolerated, without safety concerns. Robust immune responses to all components of both vaccines were produced and all criteria for non-inferiority were met, supporting the use of a 2-dose regimen of MenACWY-CRM in this age group.     

Immune response to simultaneous administration of a combined measles,mumps and rubella vaccine with booster doses of diphtheria-tetanus and poliovirus vaccine

A combined vaccine against measles (Edmonston-Zagreb 19 strain), mumps (Rubini strain) and rubella (Wistar RA 27/3 strain) was administered to a group of 46 children aged 10–12 months simultaneously with booster doses of compulsory diphtheria-tetanus toxoid and oral poliovirus vaccine. A second group of 53 children aged 15–24 months who had received booster doses of the compulsory vaccines 5 to 12 months before was also vaccinated.The same seroconversion rates (100%) and similar antibody titers for rubella were observed in both groups. The same seroconversion rates for mumps (93%) and similar rates for measles (98 and 94%) were observed in the two groups.Significantly lower antibody titers for measles and mumps were found in the first group, but they were compensated by an earlier protection, a reduction of number of visits for immunization, costs for the community, and improvement in parental compliance.These results confirm that Edmonston-Zagreb 19 and Rubini strains are still immunogenic even when they are combined with Wistar RA 27/3 strain. Moreover, a long term follow-up in order to verify the persistence of protective antibody levels in both groups of children, could suggest that combined measles, mumps and rubella vaccine could be given earlier (at 10–12 months of age), simultaneously with booster doses of diphtheria and tetanus toxoid and of trivalent oral poliovirus vaccine.