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).     

上海市麻疹、流行性腮腺炎、风疹抗体水平调查分析

[目的 ]　了解本市健康人群麻疹、腮腺炎、风疹的抗体水平。　 [方法 ]　采集 0～ 5 0岁健康人群血标本 5 43份 ,检测麻疹、腮腺炎、风疹抗体。　 [结果 ]　小于 8月龄组麻疹抗体GMT最低 ,接种麻疹疫苗后抗体GMT显著升高 (P<0 .0 0 1) ;小于 8月龄组及 8月龄组风疹抗体水平最低 ,1岁接种疫苗后风疹抗体显著升高 (P <0 .0 0 1) ,但随着年龄的增长抗体水平有所下降 ,抗体阳性率维持在 85 %以上 ;小于 8月龄组及 8月龄组流行性腮腺炎抗体水平最低 ,1岁以上各年龄组抗体水平显著上升 (P <0 .0 0 1)。　 [结论 ]　上海市现阶段实行麻疹疫苗、MMR疫苗的接种程序比较合理和有效 ,但应该进一步开展上海市育龄期妇女风疹抗体水平调查和MMR疫苗免疫持久性观察 ,研究预防未及龄儿童麻疹疫苗免疫策略、育龄期妇女接种风疹疫苗免疫策略 ,预防先天性风疹综合征     

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。     

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。     

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...     

日照市健康人群麻疹、风疹和流行性腮腺炎抗体水平调查

目的了解日照市健康人群麻疹、风疹、流行性腮腺炎(腮腺炎)抗体水平和自然感染情况。方法 2009年采集日照市开发区1～≥20岁健康人群血清标本245份,采用酶联免疫吸附试验检测麻疹、风疹和腮腺炎抗体。结果麻疹、风疹和腮腺炎抗体分别检测血清245份。麻疹抗体阳性率98.78%,几何平均滴度(GMT)1:1722.13;风疹抗体阳性率60.82%,抗体含量均值为35.30U/ml;腮腺炎抗体阳性率为84.49%,抗体含量均值为62.94U/ml。结论麻疹抗体阳性率显著高于风疹和腮腺炎抗体阳性率,风疹抗体阳性率普遍较低,3～6岁儿童的腮腺炎抗体阳性率显著低于其他健康人群。应加强儿童风疹和腮腺炎疫苗接种,提高接种率。定期开展育龄期妇女风疹疫苗接种工作。     

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.     

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.     

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.     

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.     

Rubella virus neutralizing antibody response after a third dose of measles-mumps-rubella vaccine in young adults

BackgroundThird doses of measles-mumps-rubella (MMR) vaccine have been administered during mumps outbreaks and in various non-outbreak settings. The immunogenicity of the rubella component has not been evaluated following receipt of a third dose of MMR vaccine.MethodsYoung adults aged 18–31 years with documented two doses of MMR vaccine received a third dose of MMR vaccine between July 2009 and October 2010. Rubella neutralizing antibody titers were assessed before, 1 month, and 1 year after receipt of a third dose of MMR vaccine.ResultsAmong 679 participants, 1.8% had rubella antibody titers less than 10 U/ml, immediately before vaccination, approximately 15 years after receipt of a second dose of MMR vaccine. One month after receipt of a third dose of MMR vaccine, average titers were 4.5 times higher and >50% of participants had a 4-fold boost. Response was highest among those with titers less than 10 U/ml prior to vaccination (geometric mean titer ratio = 18.8; 92% seroconversion) and decreased with increasing pre-vaccination titers. Average titers declined 1 year postvaccination but remained significantly higher than pre-vaccination levels. The proportion classified as low-positive antibody levels increased from 3% 1 month postvaccination to 24% 1 year postvaccination.ConclusionsVaccination with a third dose of MMR vaccine resulted in a robust boosting of rubella neutralizing antibody response that remained elevated 1 year later. Young adults with low rubella titers are more likely to benefit from a third dose of MMR vaccine.     

Incidence of mumps and immunity to measles, mumps and rubella among US military recruits, 2000-2004

Recent mumps outbreaks have evoked concerns of decreasing mumps immunity among adolescents and adults, including US military recruits subject to differing mumps immunization policies. To compare mumps incidence and to assess initial measles, mumps and rubella seropositivity, we conducted a cohort study among recruits from 2000 to 2004. Mumps incidence in the targeted MMR and universal MMR cohorts was 4.1 and 3.5 per 100,000 person-years, respectively, giving an incidence rate ratio of 1.16 (P=0.67). Measles, mumps, and rubella seropositivity was 84.6%, 89.5%, and 93.2%, respectively. Among recruits with measles and rubella immunity, 92.8% were mumps immune. These findings support the policy of targeting MMR immunization based upon measles and rubella serology alone.     

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.     

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.     

麻疹-流行性腮腺炎-风疹联合减毒活疫苗与流行性腮腺炎减毒活疫苗免疫学效果比较

目的比较麻疹-流行性腮腺炎（流腮）-风疹联合减毒活疫苗（Measles,Mumps and Rubella Combined Attenuated Live Vaccine;MMR）与流腮减毒活疫苗（Mumps Attenuated Live Vaccine,MuV）的免疫学效果。方法在宝鸡市选取18-24月龄未患过流腮、无MuV或含流腮成分疫苗免疫史、无接种禁忌证的健康儿童作为观察对象,将其按照所属乡分为两组,采集免疫前血清后分别接种MMR和MuV,1个月后采集免疫后血清检测流腮免疫球蛋白（Immunoglobulin,Ig）G。结果接种MMR的流腮IgG阳性率由免疫前的9.4%上升至98.8%,阳转率为98.8%,几何平均浓度（Geometric Mean Concentration,GMC）由免疫前的54.8单位（Unit,U）/毫升（ml）上升到1380.8 U/ml,增长24.2倍。接种MuV的流腮IgG阳性率由免疫前的8.3%上升至94.0%,阳转率为89.3%,GMC由免疫前的70.5 U/ml上升到611.1 U/ml,增长7.67倍。结论接种MMR和MuV均有良好的对流腮的免疫学效果。     

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.     

Outbreak of measles in medical students and determination of immune status to measles-mumps-rubella viruses

We conducted an investigation after a measles outbreak in medical students to determine the immunity of the medical students, the correlation between history and seropositivity, and measles-mumps-rubella vaccine effectiveness. After a preliminary study done during measles outbreak, a cross-sectional study was planned. Serum samples from 322 medical students were tested by enzyme-linked immunosorbent assay, vaccinated volunteers, then re-tested vaccinees. Histories of measles, mumps and rubella were taken. Of 322 students, seven students (2.2%) were seronegative to measles, 13 (4.0%) to mumps, and 13 (4.0%) to rubella. Historical information revealed 30.4% of sensitivity in measles and 34.3% in mumps, whereas 5.2% in rubella. Among those seronegative on admission and vaccinated, seroconversion rates were 100% (5/5), 90.9% (10/11), 100% (8/8) in measles, mumps and rubella vaccine, respectively. Of 265 vaccinated students parotitis was detected in one female student, arthralgia was observed in three students (1.1%) and myalgia in two (0.7%), and 240 students reported no side effects. We detected the unreliable historical screening and high seroprevalence of measles, mumps and rubella in prevaccine era for mumps and rubella and, safety of MMR vaccination in medical students in Turkey.     

潍坊市坊子区风疹和流行性腮腺炎抗体水平检测

目的了解潍坊市坊子区健康人群风疹、流行性腮腺炎（腮腺炎）抗体水平和自然感染情况。方法采集潍坊市坊子区1～≥70岁健康人群血清标本843人份,采用血球凝集抑制（HI）试验检测风疹和腮腺炎抗体。结果风疹抗体共检测血清843份,抗体阳性率83．51％,几何平均滴度（GMT）1：93．96。腮腺炎抗体共检测血清834份,抗体阳性率71．46％,GMT1：4．76。结论由于〈5岁儿童风疹感染率为58．64％,腮腺炎感染率为38．58％,建议对≤5岁儿童进行风疹和腮腺炎疫苗查漏补种工作。     

A randomized,blinded, placebo-controlled trial comparing antibody responses to homeopathic and conventional vaccines in university students

BackgroundHomeopathic vaccines are licensed in many countries but scientific data to support their use are sparse. The goal of this study was to compare the antibody response of homeopathic and conventional vaccines and placebo in young adults. We hypothesized that there would be no significant difference between homeopathic vaccines and placebo, while there would be a significant increase in antibodies in those received conventional vaccines.MethodsA randomized blinded placebo-controlled trial was conducted where 150 university students who had received childhood vaccinations were assigned to diphtheria, pertussis, tetanus, mumps, measles homeopathic vaccine, placebo, or conventional diphtheria, pertussis, tetanus (Tdap) and mumps, measles, rubella (MMR) vaccines. The primary outcome was a ≥ two-fold increase in antibodies from baseline following vaccination as measured by ELISA. Participants, investigators, study coordinator, data blood drawers, laboratory technician, and data analyst were blinded.ResultsNone of the participants in either the homeopathic vaccine or the placebo group showed a ≥ two-fold response to any of the antigens. In contrast, of those vaccinated with Tdap, 68% (33/48) had a ≥ two-fold response to diphtheria, 83% (40/48) to pertussis toxoid, 88% (42/48) to tetanus, and 35% (17/48) of those vaccinated with MMR had a response to measles or mumps antigens (p < 0.001 for each comparison of conventional vaccine to homeopathic vaccine or to placebo). There was a significant increase in geometric mean titres of antibody from baseline for conventional vaccine antigens (p < 0.001 for each), but none for the response to homeopathic antigens or placebo.ConclusionsHomeopathic vaccines do not evoke antibody responses and produce a response that is similar to placebo. In contrast, conventional vaccines provide a robust antibody response in the majority of those vaccinated.Trial Registry: NCT 02825368.