Immunity to rubella before and after vaccination against measles, mumps and rubella (MMR) at 12 years of age of the first generation offered MMR vaccination in Sweden at 18 months

In 1982, a two-dose programme of vaccination against measles, mumps and rubella (MMR) at the ages of 18 months and 12 years was introduced in Sweden. In 1992–1993, the first group of children vaccinated at 18 months reached the age of 12, i.e. the time for a second dose. In connection with this 12-year vaccination, 376 children were recruited, investigated concerning earlier MMR vaccination and bled prior to and 2 months after the immunization. Two hundred and twenty of them had a documented, earlier MMR vaccination and 156 had not. The latter were classified as unvaccinated. The antibody status against rubella was measured by the haemolysis-in-gel method. Prior to the present vaccination, 3% of the earlier vaccinated group totally lacked any sign of antibodies. In the presumably unvaccinated group, this figure was 76%. After the vaccination all children showed signs of antibody acitivity and all reached the antibody level of ≥15 international units, i.e. in our tests a zone dia. of approx 8 mm. However, the secondly vaccinated children ended up with a mean antibody level of 10.7 mm which was slightly lower than the level, i.e. 11.0 mm of those lacking earlier vaccination history and prevaccination seronegative. The earlier unvaccinated but pre-immune children reached a mean level of 11.2 mm. In general, those with relatively high, pre-vaccination, antibody levels reacted less to the booster than those with low or no pre-vaccination immunity. The booster thus appeared to restore the antibody levels of the low-titre children.     

A population profile of measles susceptibility in Tianjin,China

BackgroundMeasles is a highly infectious illness requiring herd immunity of 95% to interrupt transmission. Measles is targeted for elimination in China, which has not reached elimination goals despite high vaccination coverage. We developed a population profile of measles immunity among residents aged 0–49 years in Tianjin, China.MethodsParticipants were either from community population registers or community immunization records. Measles IgG antibody status was assessed using dried blood spots. We examined the association between measles IgG antibody status and independent variables including urbanicity, sex, vaccination, measles history, and age.Results2818 people were enrolled. The proportion measles IgG negative increased from 50.7% for infants aged 1 month to 98.3% for those aged 7 months. After 8 months, the age of vaccination eligibility, the proportion of infants and children measles IgG negative decreased. Overall, 7.8% of participants 9 months of age or older lacked measles immunity including over 10% of those 20–39 years. Age and vaccination status were significantly associated with measles IgG status in the multivariable model. The odds of positive IgG status were 0.337 times as high for unvaccinated compared to vaccinated (95% CI: 0.217, 0.524).ConclusionsThe proportion of persons in Tianjin, China immune to measles was lower than herd immunity threshold with less than 90% of people aged 20–39 years demonstrating protection. Immunization programs in Tianjin have been successful in vaccinating younger age groups although high immunization coverage in infants and children alone would not provide protective herd immunity, given the large proportion of non-immune adults.     

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.     

Antibody level after measles vaccination.

The present study was designed to estimate the level of measles IgG antibody in infants early after vaccination and in preschool children to determine their immune status. Three groups were studied: Group I, unvaccinated infants, Group II, recently vaccinated infants and Group III vaccinated preschool children. Measles IgG antibody was measured using the ELISA technique. The study showed that 90% (18/20) of the unvaccinated Group I infants were seronegative and only 10% were seropositive for measles IgG antibody representing most probably persisting maternal antibodies. Fifty percent (15/30) of recently vaccinated Group II infants were seropositive. A statistically significant higher antibody level was observed in Group II infants in comparison to those of Group I. The majority of seropositive infants of Group II (10/15 = 66.7%) showed high antibody level representing successful vaccination. Seropositives represented 77.4% (24/31) of Group III preschool children and the majority of them 75% (18/24) showed high antibody level which was significantly higher than the comparable in Group II infants, most probably due to subclinical infection in addition to successful vaccination. Fifty percent (15/30) of Group II infants and 22.6% (7/31) of Group III children were seronegative, more likely due to failure of initial vaccination.     

Salivary antibody levels in adolescents in response to a meningococcal serogroup C conjugate booster vaccination nine years after priming: systemically induced local immunity and saliva as potential surveillance tool

BackgroundIn several countries large-scale immunization of children and young adults with Meningococcal serogroup C (MenC) conjugate vaccines has induced long-standing herd protection. Salivary antibodies may play an important role in mucosal protection against meningococcal acquisition and carriage.AimTo investigate antibody levels in (pre)adolescents primed 9 years earlier with a single dose of MenC-polysaccharide tetanus toxoid conjugated (MenC-TT) vaccine and the response to a booster vaccination, with special focus on age-related differences and the relation between salivary and serum antibody levels.MethodsNine years after priming, healthy 10- (n = 91), 12- (n = 91) and 15-year-olds (n = 86) received a MenC-TT booster vaccination. Saliva and serum samples were collected prior to and 1 month and 1 year after vaccination. MenC-polysaccharide(MenC-PS)-specific antibody levels were measured using a fluorescent-bead-based multiplex immunoassay.ResultsBefore the booster, MenC-PS-specific IgG and IgA levels in saliva and serum were low and correlated with age at priming. The booster induced a marked increase in salivary MenC-PS-specific IgG (>200-fold), but also in IgA (∼10-fold). One year after the booster, salivary IgG and IgA had remained above pre-booster levels in all age groups (∼20-fold and ∼3-fold, respectively), with persistence of highest levels in the 15-year-olds. MenC-PS-specific IgG and IgA levels in saliva strongly correlated with the levels in serum.ConclusionParenteral MenC-TT booster vaccination induces a clear increase in salivary MenC-PS-specific IgG and IgA levels and persistence of highest levels correlates with age. The strong correlation between serum and salivary antibody levels indicate that saliva may offer an easy and reliable tool for future antibody surveillance.     

Pneumococcal conjugate vaccination does not induce a persisting mucosal IgA response in children with recurrent acute otitis media

AIM: In a prospective controlled study in young children with a history of recurrent acute otitis media, we analyzed the salivary IgA and IgG antibody titers upon vaccination with a 7-valent pneumococcal conjugate vaccine (PCV) given once or twice, followed by a 23-valent polysaccharide booster vaccination. METHODS: Salivary IgA and IgG antibody concentrations to vaccine serotype 6B, 14, 18C and 19F were measured by enzyme immunoassay in 38 samples of children vaccinated with PCV and 45 control samples. In the PCV group, 12 samples were taken prior to vaccination, 12 samples 4 weeks after the polysaccharide booster (8 months after the first conjugate vaccination) and 14 samples 7 months after the last vaccination (14 months after the first conjugate vaccination). In the control group 15 children were sampled at each of these three time points. RESULTS: We observed an increase in salivary IgG antibody concentrations against serotype 6B, 14, and 18C 14 months after the primary vaccination in children vaccinated with PCV twice, although this was significant for serotype 14 only. There was no increase in salivary IgG antibody in children vaccinate with PCV once nor in control children. IgA antibody titers increased significantly after 8 and after 14 months in both the pneumococcal vaccine recipients and the controls. However, the observed increase in mean antibody titers was significantly higher in control children compared to the PCV group. CONCLUSION: We suggest that repeated pneumococcal conjugate vaccination is necessary to induce an increase in salivary IgG antibodies and effectuate clearance of S. pneumoniae from the nasopharyngeal mucosa of children with recurrent acute otitis media. We hypothesize that the increase in salivary IgA is caused by the local boosting of the mucosal immune response by carriage and recurrent infections, which occurs less often in the PCV group compared to the control children.     

Immunogenicity of aerosol measles vaccine given as the primary measles immunization to nine-month-old Mexican children

Aerosol measles vaccination has been found to be more immunogenic than subcutaneous administration as a booster in school aged children, and immunogenic in 12-month-old children as a primary dose. The objective of the study was to evaluate immunogenicity to aerosol measles vaccine in 9-month-old children. METHODS: Nine-months-old infants received Edmonston-Zagreb measles vaccine by aerosol (10(3.58) CCID50/0.1 mL, estimated retained dose 10(2.81) CCID50 or subcutaneous route (10(4.28) CCID50/0.5 mL); cellular and humoral immunity and adverse events were assessed. RESULTS: Measles-specific T cell proliferative responses developed in 42% of children given aerosolized vaccine compared with 67% of those who received subcutaneous vaccine (p = 0.01); the mean stimulation index (SI) was 4.4+/-0.7 versus 6.9+/-1, respectively, (p = 0.05). Seroconversion rates were 33 and 92% after aerosol or subcutaneous immunization (p < 0.001). Among infants who developed serologic responses, measles geometric mean titers (GMT; 95% CI) by neutralizing antibody assay were 215 mIU/mL (115-400) in aerosol vaccine recipients and 411 mIU/mL (345-490) in those given subcutaneous vaccine (p = 0.06). CONCLUSIONS: The proportion of 9-month-old infants who developed cellular and/or humoral immunity to measles was lower in the aerosol group but measles antibody and T cell responses were comparable among those who developed measles immunity. Differences in response rates are attributable to the lower aerosol dose. Improving aerosol delivery or increasing the dose may enhance immunogenicity of primary aerosol measles vaccination in this age group.     

Salivary antibody response to vaccination with meningococcal A/C polysaccharide vaccine in previously vaccinated and unvaccinated Gambian children

Development of salivary antibodies at the age of 4 or 5 years to group A and C meningococcal polysaccharides (MenA/C PS) was studied among Gambian children, who had received MenA/C conjugate or PS vaccine in infancy. There was also a control group of 64 age matched children. IgG, IgA, and secretory Ig concentrations were measured by enzyme immuno assay. MenA/C PS vaccine induced antibodies both in previously vaccinated and unvaccinated children. The previous vaccination had not induced long lasting IgA-mediated memory. IgA antibodies were secretory, and most of IgG was serum derived. The IgG salivary response seen was similar to the serum response.     

Detection of anti-protective antigen salivary IgG antibodies in recipients of the US licensed anthrax vaccine

The immune response of anthrax vaccine recipients is not routinely monitored. For field use, a noninvasive test would be beneficial to evaluate the antibody response of anthrax-vaccinated individuals working within a high-risk area of possible exposure. The aim of this cross-sectional study was to determine whether whole saliva can be used as a surrogate matrix for the detection of 83 kDa protective antigen (PA)-specific immunoglobulin G (IgG). An enzyme-linked immunosorbent assay was used for the detection of PA-specific IgG in matched samples (serum and saliva) that were collected from vaccinated and unvaccinated participants. Specimens from 180 individuals revealed a positive correlation (r=0.73; P<0.0001) between the level of PA-specific antibody detected in the saliva and serum. The number of vaccinations influenced both the saliva and serum antibody response. On average, the concentration of serological PA-specific antibodies in the vaccinated group was nearly 1600-fold greater than that in saliva. The magnitude of the salivary anti-PA antibody response was not significantly affected by the consumption of food, beverage, or tobacco products or other factors, which could potentially affect oral fluid properties. These results suggest that an oral fluid-based immunoassay may be a feasible alternative to monitoring the serological antibody response of individuals that have been vaccinated against anthrax.     

Waning antibodies in measles and rubella vaccinees--a longitudinal study

The evolution of measles- and rubella-specific serum IgG was followed in a longitudinal study in 224 young adolescent vaccinees, with or without boost vaccination before or during the 6.8-year observation period. Antibody titres were monitored by enzyme immuno assay (Enzygnost, Dade-Behring). After revaccination (second dose) rubella seropositivity rate increased from 92.1 to 100%, whereas measles seroprevalence (about 90%) did not significantly change between the paired sera. Significantly higher IgG (> three-fold) in the second serum of 5.2% (measles) and 7.8% (rubella) of participants with low antibodies (measles: < 1500 mIU; rubella < 40 IU) in first serum, suggest a secondary immune response (SIR) during the study period, only partially explained by revaccination. Excluding individuals with SIR, minimal annual antibody decay rates of -2.9% (confidence interval, CI: -0.7 to -4.8%) for rubella and -1.6% (CI: -0.1 to -3%) for measles were determined in participants with single dose vaccination. Thus, two-dose vaccination was adequate to protect women from rubella infection at least during childbearing age. Similarly only few individuals may become seronegative for measles again after successful vaccination due to minimal waning of low antibody levels (< 1500 mIU). However, as a result of a more rapid decay of high-titre (> 1500 mIU) antibodies (-2.4%/year), many vaccinees may eventually become susceptible to vaccine-modified measles (VMM) and consequently complicate measles control strategies.     

A measles outbreak from an index case with immunologically confirmed secondary vaccine failure

During the elimination stage of measles, the development of such disease in individuals who received measles-containing vaccine (MCV) is a concern from an epidemiological standpoint. A few cases in which measles was transmitted from a patient who received two doses of MCV have been reported. However, whether such transmissions were caused by primary vaccine failure (PVF) or secondary vaccine failure (SVF) remains unclear. All patients suspected of measles in Osaka Prefecture between November and December 2018 were enrolled. Data about age, gender, immunization record, and clinical signs were obtained. Laboratory examinations were performed, which included virus isolation in tissue culture, a nucleic acid test based on virus-specific real-time polymerase chain reaction and humoral responses to the measles virus measuring immunoglobulin (Ig) M, IgG, avidity of IgG, and neutralizing antibody concentration. The measles outbreak comprised 10 laboratory confirmed cases, including three secondary and six tertiary patients. Among them, three secondary patients were unvaccinated. The index case had received two MCV doses, and the six tertiary patients were vaccinated. Both the index and tertiary patients had high specific IgG concentration with high avidity. In particular, the index patient had a markedly high neutralization antibody concentration of 425,590 mIU/mL, which indicated immunological SVF. This study first reported about measles transmission from an individual with SVF who received two vaccination doses. To prevent measles transmission and outbreak particularly in countries where measles was almost eliminated, patients with SVF for measles should be cautiously monitored.     

Measles antibodies in cord blood in Portugal: Possible consequences for the recommended age of vaccination

The optimum age to give the first dose of measles vaccine must balance the risks of disease and vaccine failure. Both are influenced by the levels of transplacentally acquired maternal antibodies. This study was conducted in the Obstetric service of Portuguese hospital, in 2012–2013. Mothers were recruited after informed consent. Measles IgG was measured in 206 cord sera, using a commercial immunoassay. Geometric mean concentrations (and 95% CI) were 1849 mIU/ml (1196–2857) and 790 mIU/ml (618–1008) in cord sera of newborns from unvaccinated and vaccinated mothers respectively. Maternal age and vaccination status were both associated with the concentration in cord sera, but maternal age was the major predictor. The likely explanation is the same already mentioned in other studies: as a vaccination program progresses, vaccination coverage increases as measles incidence decreases. That results newborns from younger vaccinated mothers having less measles antibodies while the older mothers are more likely to have been infected with the wild virus. As the proportion of vaccinated mothers increase, developed countries tend to anticipate the recommended age of the first dose to 12 months of age. Models using hypothetical measles antibody decay rates in infancy were explored. Anticipating the first dose of MMR1 in Portugal to the age of 12 months might have not been the best decision but results were not conclusive, and arguments supporting or not the anticipation were discussed.     

A study of maternally derived measles antibody in infants born to naturally infected and vaccinated women.

Maternal, cord and infant measles antibody levels were measured and compared in a group of 411 vaccinated mothers and 240 unvaccinated mothers, and their babies, between 1983 and 1991. Maternal and cord sera were tested by haemagglutination inhibition and/or enzyme-linked immunosorbent assay, and plaque reduction neutralization tests were also used to test infant sera. Geometric mean titres were significantly higher in the unvaccinated than in the vaccinated mothers (P < 0.001). Infants born to mothers with a history of measles had higher antibody levels at birth than infants of vaccinated mothers and, although the difference narrowed over time, continued to have higher levels up to 30 weeks of age. Between 5 and 7 months of age significantly more of the children of vaccinated mothers had plaque reduction neutralization antibody levels below that which would interfere with vaccination. As the boosting effect of circulating natural measles disappears, earlier measles vaccination may need to be considered, perhaps as part of a two-dose policy.     

Study of incidence of measles and vaccination coverage in Ahmedabad urban slums

Measles incidence and vaccination coverage survey was carried out in Ahmedabad urban slums in February 2000. A total of 3073 children between 9 to 59 months were studied. The incidence rate of measles was 11.2% (95% C.I-10.04-12.36). Measles vaccination coverage was only 59.88%. There was no gender difference in vaccine coverage or measles incidence rate. Diarrhoea was the most common complication observed among both vaccinated and unvaccinated children and it was significantly more among unvaccinated children. Among 1840 vaccinated children only 529 (28.75%) children received vitamin A along with measles vaccination.     

Stunting correlates with high salivary and serum antibody levels after 13-valent pneumococcal conjugate vaccination of Venezuelan Amerindian children

ObjectiveTo determine the impact of pre-vaccination nutritional status on vaccine responses in Venezuelan Warao Amerindian children vaccinated with the 13-valent pneumococcal conjugate vaccine (PCV13) and to investigate whether saliva can be used as read-out for these vaccine responses.MethodsA cross-sectional cohort of 504 Venezuelan Warao children aged 6 weeks – 59 months residing in nine geographically isolated Warao communities were vaccinated with a primary series of PCV13 according to Centers for Disease Control and Prevention (CDC)-recommended age-related schedules. Post-vaccination antibody concentrations in serum and saliva of 411 children were measured by multiplex immunoassay. The influence of malnutrition present upon vaccination on post-vaccination antibody levels was assessed by univariate and multivariable generalized estimating equations linear regression analysis.ResultsIn both stunted (38%) and non-stunted (62%) children, salivary antibody concentrations correlated well with serum levels for all serotypes with coefficients varying from 0.61 for serotype 3–0.80 for serotypes 5, 6A and 23F (all p < 0.01).Surprisingly, higher serum and salivary antibody levels were observed with increasing levels of stunting in children for all serotypes. This was statistically significant for 5/13 and 11/13 serotype-specific serum and saliva IgG concentrations respectively.ConclusionStunted Amerindian children showed generally higher antibody concentrations than well-nourished children following PCV13 vaccination, indicating that chronic malnutrition influences vaccine response.Saliva samples might be useful to monitor serotype-specific antibody levels induced by PCV vaccination. This would greatly facilitate studies of vaccine efficacy in rural settings, since participant resistance generally hampers blood drawing.The study was registered in a primary registry of the World Health Organization with identifier number RPCEC00000158.     

A large observational study to concurrently assess persistence of measles specific B-cell and T-cell immunity in individuals following two doses of MMR vaccine

The measurement of measles-specific neutralizing antibodies, directed against the surface measles virus hemagglutinin and fusion proteins, is considered the gold standard in measles serology. We assessed functional measles-specific neutralizing antibody levels in a racially diverse cohort of 763 young healthy adolescents after receipt of two doses of measles-mumps-rubella vaccine, by the use of an automated plaque reduction microneutralization (PRMN) assay, and evaluated their relevance to protective antibody levels, as well as their associations with demographic and clinical variables. We also concurrently assessed measles-specific IFNγ Elispot responses and their relation to the observed antibody concentrations. The geometric mean titer for our cohort was 832mIU/mL (95% CIs: 776; 891). Sixty-eight subjects (8.9%) had antibody concentrations of less than the protective threshold of 210mIU/mL (corresponding to PRMN titer of 120; suggesting protection against symptomatic disease), and 177 subjects (23.2%) demonstrated persisting antibody concentrations above 1841mIU/mL (corresponding to PRMN titer of 1052; suggesting total protection against viral infection), 7.4 years after vaccination, in the absence of wild-type virus boosting. The mean measles-specific IFNγ Elispot response for our cohort was 46 (95% CIs: 43; 49) IFNγ-positive spots per 200,000 cells with no relation of cellular immunity measures to the observed antibody concentrations. No significant associations between antibody titers and demographic and clinical variables, including gender and race, were observed in our study. In conclusion, in a large observational study of measles immunity, we used an automated high-throughput measles virus-specific neutralization assay to measure humoral immunity, and concurrently determined measles-specific cellular immunity to aid the assessment of potential susceptibility to measles in vaccinated populations.     

合肥市某计免门诊儿童麻疹疫苗免疫后抗体水平分析

目的了解麻疹疫苗初免1针后抗体阳转率水平与麻疹疫苗初免和加强接种2针后的抗体阳转率水平，评价麻疹疫苗的接种质量和复种效果。方法采用ELISA方法检测血清麻疹IgG抗体，把某计免门诊343名儿童抗体水平监测资料和合肥市3818名儿童抗体水平监测资料进行比较。结果该计免门诊儿童以及合肥市总体儿童在接种2针麻疹疫苗后抗体阳转率均高于接种1针麻疹疫苗后的抗体阳转率，（X2分别为8．86和14．59，P均小于0．01）差异均有显著性意义。结论麻疹疫苗复种能明显提高抗体阳转率。     

Transplacental transfer of measles and total IgG.

This study was conducted to evaluate factors affecting the levels of total IgG (tIgG) and measles specific IgG (mIgG) in mother and cord sera, and the efficiency of transplacental transport of tIgG and mIgG. The study was conducted in four hospitals in Oporto, Portugal, where 1539 women and their newborns were enrolled. Measles IgG levels were lower among vaccinated mothers and respective cord sera than among vaccinated counterparts. Cord mIgG was strongly correlated with maternal levels in both vaccinated and unvaccinated groups. Transplacental transport efficiency (TTE) of mIgG decreased with increasing maternal levels, although almost one third of the observed effect was due to measurement error. The TTE was not affected by vaccination status. Monitoring maternal measles antibody levels and maternal vaccination status could be useful to determine when the age for measles vaccination can be reduced.     

我院临产孕妇麻疹病毒保护性抗体水平研究

目的研究临产孕妇血清麻疹病毒（Measles virus,MV）保护性抗体水平,为预测母传抗体对婴幼儿的保护作用提供科学依据。方法酶联免疫吸附试验定量检测临产孕妇血清MV Ig G抗体水平,对结果进行统计分析。结果研究时段内共有419名临产孕妇,MV Ig G范围为5.5~28208.5m IU/m L,几何均数为1405.2±2202.9 m IU/m L,MV Ig G阳性率为89.50%,但MV Ig G对胎儿达保护性水平（超过1000 m IU/ml）者仅占44.39%;非杭州籍孕妇MV Ig G抗体达到对胎儿保护性水平的率显著高于杭州籍孕妇（P〈0.05）。结论本研究中的临产孕妇体内MV Ig G抗体处低水平,对胎儿的保护率低,建议育龄妇女孕前常规进行麻疹疫苗接种。     

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.