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.     

Immunogenicity and safety of a combined DTaP-IPV vaccine compared with separate DTaP and IPV vaccines when administered as pre-school booster doses with a second dose of MMR vaccine to healthy children aged 4-6 years

Combination vaccines represent one solution to the problem of increased numbers of injections during single clinic visits. A combined DTaP-IPV (Infanrix-IPV) vaccine has been developed for use as a pre-school booster. Four hundred healthy children aged 4-6 years previously primed with 4 doses of DTaP vaccine (Infanrix), 3 doses of poliovirus vaccine and 1 dose of MMR vaccine were randomized to receive single doses of either the combined DTaP-IPV vaccine or separate DTaP and IPV vaccines in a Phase II trial (DTaP-IPV-047). All children also received a second dose of MMR vaccine. Immunogenicity was assessed in serum samples taken before and 1 month after booster administration. Safety was actively assessed for 42 days post-vaccination. Non-inferiority of the DTaP-IPV vaccine to separate DTaP and IPV vaccines was demonstrated for all DTaP antigen booster response rates and poliovirus geometric mean titers of antibody ratios. Post-vaccination, > or =99.4% of children in both groups had seroprotective levels of anti-diphtheria and anti-tetanus antibodies (> or =0.1IU/mL) and seroprotective anti-poliovirus antibody titers (> or =1:8). All children in both groups were seropositive for measles, mumps and rubella antibodies, with similar post-vaccination geometric mean concentrations/titers. No significant differences were observed in the incidence of solicited local or general symptoms, unsolicited symptoms and serious adverse events between the two groups. This combined DTaP-IPV appeared safe and immunogenic when given as a booster dose at 4-6 years of age. The DTaP-IPV vaccine had no negative effect on the response to co-administered MMR vaccine, making it well-suited for use as a pre-school booster.     

Antibody persistence in children aged 6–7 years one year following booster immunization with two MMR vaccines applied by aerosol or by injection

ImportanceIn a previous study on booster vaccination, we reported that two aerosolized MMR vaccines were as safe and immunogenic as injectable vaccines containing the same antigens. We now present results of antibody persistence one year after immunization.ObjectiveTo assess the antibody persistence for measles, mumps, and rubella one year following booster immunization.MethodsWe performed clinical and serological follow-up of participants in a previous study of Mexican children aged 6–7 years, in which participants were randomized to four groups receiving, by aerosolized or by injection, the MMR SII vaccine (Serum Institute of India), or the MMR II (Merck Sharp & Dhome). We evaluated the antibody persistence by PRN test for measles and by ELISA for rubella and mumps. The occurrence of clinical events was evaluated via periodic visits of a nurse team to children’s schools and homes.ResultsOf the 260 initial participants, 241 completed one-year follow-up. There were only statistically significant differences in baseline seropositivity for mumps. One year after immunization, seropositivity in all groups was 100% for measles and rubella. The seropositivity rank for mumps was from 90.3% for the injected vaccine MMR II to 96.6% for vaccine MMR SII applied by aerosol; these differences were not statistically significant. With exception of the aerosolized vaccine MMR SII for the geometric mean titer (GMT) for measles, all study groups presented declination of GMT for the three viruses. The difference between the aerosolized vaccines MMR SII and MMR RII was statistically significant for mumps antibodies. Only mild clinical events were identified.ConclusionUnder conditions of no endemic transmission for measles and rubella, and of low circulation of mumps virus, school-aged children remained seropositive to the three viruses one year following booster immunization.The study was registered under CMN 2010-005 number at COFEPRIS (National Regulatory Authority).     

Vaccination coverage among children enrolled in Head Start programs or day care facilities or entering school.

PROBLEM/CONDITION: Undervaccinated children enrolled in day care centers and schools are vulnerable to outbreaks of vaccine-preventable diseases. A Healthy People 2000 objective is to increase to > or = 95% vaccination coverage among children attending licensed day care facilities and kindergarten through postsecondary school (objective 20.11). REPORTING PERIOD COVERED: September 1997-June 1998. DESCRIPTION OF SYSTEM: CDC's National Immunization Program administers grants to support 64 vaccination programs. These programs are in all 50 states, eight territories or jurisdictions (American Samoa, Republic of Marshall Islands, Federated States of Micronesia, Guam, Commonwealth of Northern Mariana Islands, Puerto Rico, Republic of Palau, and the U.S. Virgin Islands), five cities (Chicago, Houston, San Antonio, New York City, and Philadelphia), and the District of Columbia. Grant guidelines require annual school vaccination surveys and biennial surveys of Head Start programs and licensed day care facilities. This system constitutes the only source of nationally representative vaccination coverage estimates for these populations. RESULTS: Head Start Programs: Of the 64 reporting areas, 33 (51.6%) submitted coverage levels for children enrolled in Head Start programs. Of these, all 33 programs reported coverage levels for diphtheria and tetanus toxoids and pertussis vaccine (DTP), diphtheria and tetanus toxoids (DT), or tetanus toxoids (Td), poliovirus vaccine, and measles vaccine; and 32 reported coverage levels for mumps and rubella vaccines. Four programs reported coverage levels for the combined measles, mumps, and rubella vaccine (MMR). The mean vaccination coverage levels for the 1997-98 school year among the reporting vaccination programs were 97.8% for poliovirus vaccine (range: 80.0%-100.0%), 97.0% for DTP/DT/Td (range: 87.7%-100.0%), 93.3% for measles vaccine (range: 91.4%-100.0%), and 93.2% for mumps and rubella vaccines (range: 91.4%-100.0%). Licensed Day Care Facilities: Of the 63 reporting areas with licensed day care facilities, 38 (60.3%) submitted coverage levels for enrolled children. Of these, all 38 programs reported coverage levels for poliovirus vaccine and DTP/DT/Td, 37 reported coverage levels for measles vaccine, and 36 reported coverage levels for mumps and rubella vaccines. Four programs reported coverage levels for the combined MMR. The mean vaccination coverage levels among the reporting areas were 95.8% for poliovirus vaccine (range: 85.1%-99.8%), 95.7% for DTP/DT/Td (range: 77.6%-99.9%), 89.1% for measles vaccine (range: 78.0%-99.9%), and 89.1% for mumps and rubella vaccines (range: 78.0%-99.9%). Kindergarten/First Grade: Of the 64 reporting areas, 43 (67.2%) submitted coverage levels for children enrolled in kindergarten and first grade. Of these 43 programs, 42 reported coverage levels for poliovirus vaccine and DTP/DT/Td, and 43 reported coverage levels for measles, mumps, and rubella vaccines. Four of the 43 programs reported coverage levels for the combined MMR. The mean vaccination coverage levels among the reporting areas were 96.7% for poliovirus vaccine (range: 82.8%-99.9%), 96.7% for DTP/DT/Td (range: 82.8%-99.8%), 96.0% for measles vaccine (range: 82.8%-99.9%), and 96.5% for mumps and rubella vaccines (range: 82.8%-99.9%). INTERPRETATION: High levels of vaccination coverage among children entering school most likely result from the successful implementation of state-specific school vaccination laws, which have applied to children entering school in all states and the District of Columbia since at least 1990. All states, territories, and the District of Columbia have additional laws that require vaccination of children in licensed day care facilities. However, because a high proportion of states and territories did not submit vaccination coverage reports to CDC, these estimated means may not reflect levels for all children in the United States.     

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.     

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...     

A randomised single blind trial of a combined mumps measles rubella vaccine to evaluate serological response and reactions in the UK population

Four hundred and twenty children were randomly assigned to receive either mumps measles rubella (MMR) vaccine (207) or measles vaccine (213) in a single blind study, to investigate the reactogenicity and serology of the MMR vaccine. There was no significant difference between the number of children developing symptoms after MMR vaccination to those developing symptoms after measles vaccination. Both vaccines are associated with a rash, temperature and restlessness five to thirteen days after vaccination. The serological response to measles vaccine was similar in both groups with 92-6% seroconverting with MMR, and 96-8% with measles. Seroconvertion against mumps and rubella with the MMR vaccine was 88% and 96% respectively. This study confirms the safety and efficacy of the MMR vaccine in a UK population.     

Antibodies to measles,mumps, and rubella virus in Thai children after two-dose vaccination at 9 months and 2.5 years: A longitudinal study

IntroductionThailand changed the schedule of childhood measles–mumps–rubella (MMR) vaccination in 2014, moving the second dose from the age of 6 years to 2.5 years. There are currently no data on antibody responses to the MMR vaccine since this recommendation.Material and methodsWe investigated antibody responses in a cohort of children who received two doses of MMR vaccine at the ages of 9 months and 2.5 years that was originally established to evaluate antibody levels to Bordetella pertussis antigens (ClinicalTrials.gov no. NCT02408926). Infants were born to mothers who previously received tetanus–diphtheria–acellular pertussis vaccine at 27–36 weeks of gestation. Anti-measles, -mumps, and -rubella virus IgG levels were measured at birth (cord blood) and the ages of 2 and 7 months (before the first MMR vaccination); 18 and 24 months (9 and 15 months, respectively, after the first dose); and 36 months (6 months after the second dose) using commercially available enzyme-linked immunosorbent assay kits.ResultsAt 7 months of age, 96.2%, 99.6%, and 98.8% of infants had no protection against measles, mumps, and rubella, respectively. Levels of antibody against all three antigens increased significantly after the first but not the second dose. At 6 months after two-dose vaccination, 97.4%, 84.8%, and 78.7% of children remained seroprotected against measles, mumps, and rubella, respectively.ConclusionsMaternally derived antibodies to measles, mumps, and rubella virus disappeared by the age of 7 months in Thai children. Two-dose MMR vaccination at 9 months and 2.5 years of age induced robust immune responses against these viruses.     

Persistence of antibodies in 4-8 year old Austrian children after vaccination with hexavalent DTaP-HBV-IPV/Hib and MMR vaccines

To determine the proficiency of the Austrian childhood vaccination schedule to induce long lasting seroprotection against vaccine preventable diseases a seroepidemiological study in 348 children between four and eight years of age was conducted. Antibodies against diphtheria, tetanus, pertussis, hepatitis B, measles, mumps and rubella antigens were assessed in children, who had been vaccinated with hexavalent DTaP-HBV-IPV/Hib vaccines at three, four, five months and in the second year of life and/or MMR vaccines in the second year of life at least once, but mostly twice.High seroprotection rates (SPRs) were detected for tetanus (96%) and measles (90%). SPRs regarding diphtheria and mumps were 81% and 72%, respectively. Rubella-SPRs were 68% in females and 58% in males. Hepatitis B-antibody levels ≥10 mIU/mL were present in 52%; antibodies against pertussis were detected in 27% of the children. SPRs for measles and rubella depended on the interval since last vaccination; mumps-antibodies were significantly lower after one MMR-vaccination only. Antibodies against diphtheria, tetanus and pertussis depended on the interval since last vaccination while HBs-antibodies did not. The low levels of antibodies 1-7 years after vaccination against pertussis, rubella and mumps after only one vaccination should be considered when recommending new vaccination schedules.     

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.     

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.     

Seroprevalence of measles,mumps and rubella among children in American Samoa, 2011, and progress towards West Pacific Region goals of elimination

Introduction

In line with the global goals for measles elimination, countries in the West Pacific Region (WPR) have set a goal to eliminate measles by 2012. Due to its contagiousness, high population immunity is needed for achieving and documenting measles elimination. We assessed population immunity to measles, mumps and rubella among first grade children in American Samoa (AS) through a seroprevalance study.

Methods

Using commercial indirect enzyme-linked immunosorbant IgG assays (Wampole Laboratories, Cranbury, NJ) we determined IgG antibodies against the measles, mumps, and rubella (MMR) viruses in sera collected from first grade students in AS in April–May 2011. Vaccination status was retrieved from the immunization cards. Factors associated with seropositivity of measles, mumps, and rubella were analyzed separately.

Result

Among 509 first grade students, measles, mumps, and rubella seroprevalence were 92%, 90%, and 93%, respectively. The proportions of first grade students with documented one or two doses of MMR vaccine were 93% and 84%, respectively. The vaccination status of 6% of the first graders was unknown and 1% was unvaccinated. Receiving two-doses of MMR vaccines was associated with high measles and mumps seropositivity (p < 0.01).

Conclusion

The high measles seroprevalence among children shows the progress by American Samoa towards measles elimination. Achieving and maintaining high two-dose MMR vaccine coverage in all age groups will aid in attaining the measles elimination status and prevent transmission of measles from potential imported measles cases from other countries.     

Antibody persistence in young adults 1 year after MMR immunization by aerosol or by subcutaneous route

Information on antibody persistence after aerosol revaccination with MMR components is limited. Thus, antibody titers were determined in 283 adult participants in a MMR vaccine trial 12 months after revaccination. One group had received aerosolized Triviraten vaccine while two other groups received either injected Triviraten or MMR II vaccine. Both MMR vaccines contained the same rubella strain, but different measles and mumps strains. Seropositivity to measles persisted in 98% of aerosolized vaccine recipients, 92% of injected Triviraten, and 95% of injected MMR II. All participants in the three groups retained seropositivity to rubella, while less than 50% remained seropositive to mumps.     

Response to measles revaccination among toddlers in Saudi Arabia by the use of two different trivalent measles-mumps-rubella vaccines.

This trial confirmed the immunogenicity of a standard dose of measles vaccine Edmonston-Zagreb strain administered at the age of 6 months as evaluated serologically at 12 months of age in 94 healthy children in Saudi Arabia. The residual seropositivity rate for measles was 53.4 and 80.6% as measured by enzyme immunoassay (EIA) and plaque neutralization, respectively, and could be increased to virtually 100% seroprotection after immunization with 1 of 2 measles-mumps-rubella (MMR) vaccines (Triviraten Berna or MMR II MSD) at 12 months of age. In both groups, more than 90% of infants showed an immune response to the mumps and rubella vaccine strains at 14 months of age. There was a difference in the geometric mean titres of mumps antibodies in favour of MMR II (P < 0.001). The seroconversion rates for mumps antibodies differed between the 2 vaccines because of the different test systems and/or the different cut-off levels used. The study reconfirmed that for the assessment of Rubini mumps vaccine-induced antibodies the indirect immunofluorescence test is superior to the EIA. The systemic tolerability of both vaccines was excellent. Triviraten Berna is exclusively propagated on human diploid cell cultures and hence free of avian proteins.     

Vaccination coverage among children in kindergarten--United States, 2006-07 school year

Healthy People 2010 objectives include increasing vaccination coverage among children in kindergarten and first grade (objective 14-23). For these children, the target is >/=95% vaccination coverage for the following: hepatitis B vaccine; diphtheria and tetanus toxoids and pertussis vaccine, diphtheria and tetanus toxoids and acellular pertussis vaccine, or diphtheria and tetanus toxoids vaccine (DTP/DTaP/DT); poliovirus vaccine; measles, mumps, and rubella (MMR) vaccine; and varicella vaccine. To assess progress toward national goals and determine vaccination coverage among children in kindergarten, data were analyzed from reports submitted to CDC by 49 states and the District of Columbia (DC) for the 2006-07 school year. This report summarizes findings from that analysis, which indicated that approximately 75% of states have reached the 2010 objective of at least 95% coverage for all of the vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) for children in kindergarten. These results underscore the effectiveness of school-entry requirements in increasing vaccination coverage but highlight a need for more standardized vaccination reporting among states.     

Vaccination coverage among children entering school--United States, 2005-06 school year

One of the national health objectives for 2010 is to achieve and sustain > or =95% vaccination coverage among children in kindergarten through first grade for the following vaccines: hepatitis B vaccine; diphtheria and tetanus toxoids and pertussis vaccine, diphtheria and tetanus toxoids and acellular pertussis vaccine, or diphtheria and tetanus toxoids vaccine (DTP/DTaP/DT); poliovirus (polio) vaccine; measles, mumps, and rubella vaccines; and varicella vaccine. To determine vaccination coverage among children entering kindergarten, data were analyzed from reports submitted to CDC by states and the District of Columbia (DC) for the 2005-06 school year. This report summarizes the results of that analysis, which indicated that coverage for each vaccine was reported to have exceeded 95% in more than half of the states.     

The control of mumps in Israel

Background: Measles–mumps–rubella (MMR) vaccine replaced monovalent measles vaccine in the routine childhood vaccination schedule in Israel in December 1988, primarily to achieve the elimination of the congenital rubella syndrome. In this observational study, we report on changes in reported mumps incidence in Israel from the time of the introduction of MMR vaccine until the end of 1998. Methods: The report is based upon passive national surveillance of mumps incidence, which has been notifiable in Israel since 1977. Results: Reported mumps incidence in Israel is now less than 2% the pre-vaccine incidence. Conclusions: In the decade since the introduction of routine mumps vaccination in 1-year-olds in Israel, mumps control has been achieved. Although small outbreaks occur and may continue to occur in future years, because of undervaccination of children, primary vaccine failure and waning immunity, it can tentatively be said that mumps is no longer a public health problem in Israel.     

冻干麻疹-腮腺炎-风疹三联活疫苗免疫安全性及免疫学效果观察

目的 观察卫生部北京生物制品研究所研制的麻疹-腮腺炎-风疹（北京MMR）疫苗的免疫学效果。方法 分别选择10-12岁，2-2.5岁和8-12月龄儿童，接种北京MMR（实验疫苗），并与进口MMR疫苗，麻疹疫苗，腮腺炎疫苗和风疹疫苗（对照疫苗）相比较，开展该疫苗的免疫安全性和免疫原性观察研究。结果 在32名2岁以上较大龄儿童接种北京MMR疫苗无副反应发生后，对104名8-12月龄婴儿接种该疫苗，仅有6.7%和1.9%的儿童分别发生一过性发热（中低反应）和皮疹，无其他不良反应发生，北京MMR疫苗免疫接种后，其麻疹，风疹，腮腺炎HI抗体阳转率分别为100%，100%和85.7%;GMT分别为41，320和6.1，分别与对照疫苗相比，差异多无显著性。结论 北京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和免疫原性，且可以作为麻疹的基础免疫和复种疫苗使用。     

A comparison of booster immunisation with a combination DTPa-IPV vaccine or DTPa plus IPV in separate injections when co-administered with MMR, at age 4-6 years

This study evaluated GSK's combined DTPa-IPV vaccine (Infanrix-IPV) given as a fifth consecutive acellular pertussis booster dose in conjunction with the second dose of MMR vaccine (Priorix) in children aged 4-6 years. The immunogenicity and reactogenicity of this vaccine regimen was compared with separate injections of DTPa and IPV when given concomitantly with MMR. A cohort of 362 children previously primed with four doses of DTPa and OPV, and a single dose of MMR were randomized to receive either DTPa-IPV+MMR (N=181) or DTPa+IPV+MMR (N=181). Antibody concentrations were measured prior to and 1 month after the booster dose. After immunisation all subjects from both groups had seroprotective antibody levels against diphtheria, tetanus and the three poliovirus serotypes, > or = 96% showed vaccine response to PT, FHA and PRN, all were seropositive to mumps and rubella, and all but one subject were seropositive to measles. Immunogenicity results for each component antigen were similar for DTPa-IPV and separately co-administered DTPa and IPV. Local reactions were common with 24.0% and 31.1% of children experiencing swelling >50mm at the DTPa-IPV and DTPa injection sites, respectively. The DTPa-IPV combination did not increase the incidence or intensity of adverse events compared with separately administered DTPa+IPV. The response to the concomitantly administered MMR vaccine was similar in the two groups and similar to previously reported responses for a second dose of MMR. This combined DTPa-IPV vaccine has a similar reactogenicity profile to DTPa, is immunogenic when given as a booster dose at 4-6 years of age, and has no impact on the immunogenicity of a co-administered second dose of MMR vaccine.