In this study, nearly 85% of investigated mothers were serologically immune to MMR viruses. Also, few more than 12 months’ infants showed seroprotection against these agents before their scheduled MMR1 vaccination. After administering the MMR1 to more than 12 month- old children, nearly 84, 6 %, 82,7 % and 78.8 % of vaccinated children responded to three components of MMR1 vaccine, respectively and seroconverted. Six months after the initial MMR immunization, most serosusceptible children showed immunologic response to MMR2 and serologicaly achieved protection to MMR agents. Also, their earlier acquired seroimmunity following first dose of MMR vaccine injection was boosted. Finally, following administering 2- doses of MMR vaccine to children after the age of 12 months, approximately 94.8%, 89.7% and 92.3% of vaccinees acquired seroprotection to measles, mumps, and rubella, respectively.
Since primary protection against infectious diseases is provided mainly by maternal IgG antibodies transferred actively via placenta to the fetus, higher maternal antibodies are associated with increased levels of antibodies in the offspring. However, these antibodies disappear during first few months of life. Higher levels will persist for a longer time. Giving booster doses of vaccine or natural exposure to these agents among childbearing age women, can result in robust of their specific immunity and consequently higher levels of passive immunity will appear in the infants. Therefore, the concentrations of specific antibodies, particularly anti-measles in the infants may vary widely in the world [32, 33].
Based on this study findings, most participated mothers were seropositive against three agents of vaccine. In addition to history of measles immunization during childhood, majority of our mothers were reimmunized in the national program of MR campaign conducted at the December 2003 [21]. However, none of these mothers were immunized against mumps earlier and their immunity against mumps is the results of natural infection. Level of antibody achieved by natural infections is usually higher and it persists for a longer time compare to vaccine - induced immunity [32]. Therefore, this may explain the high rates of immunity against mumps observed in our studied mothers. The high rates of immunity against measles and rubella may be due to positive impact of MR reimmunization performed 13-to15years earlier or it could be the result of exposure to natural infection in the past. Similar results are reported recently among Iranian childbearing age women with the same age [34]. In a nationwide seroprevalence study among Iranian girl at the verge of marriage that were MR reimmunized 13-14years earlier, results showed that 80,7% (70.3-to 89.5%) and 90.6% (81.2-to 95%) were immune to measles and rubella, respectively. There was a sharp difference between those who were MR vaccinated and those who were not. They concluded that these high rates of seroimmunity were the positive impact of MR revaccination [34].
According to our data, a few children were seroimmune to MMR agents just before MMR1 vaccination detected by ELISA method. The exact origin of these antibodies is not clear, but most probably is maternal. In a similar study from the region among 112 mother-infant pairs in year 2008, (5-years after the national MR campaign), nearly 6.2% and 10.7% of 12 month- old infants, all from MR reimunized mothers, retained their seroimmunity to measles and rubella, respectively [35]. Also, in another similar study from southeast of Iran, nearly 3.7% of 12 months old infants just before MMR1 vaccination were serologically immune to measles detected by ELISA[30]. The point of concern is that ELISA methods is not sensitive enough to detect low titers of measles antibodies. Therefore, if more sensitive methods are used, higher proportion of infants may retain their passive immunity just before MMR1 immunization [36]. MMR vaccine is a live attenuated vaccine and presence of specific antibodies could negatively impact on the immunogenicity of the person. After giving scheduled MMR1 vaccine to more than 12 month- old seronegative children in this study, nearly 15%, 17%, and 21%, of vaccinated children remained seronegative to MMR agents, respectively [primary vaccine failure (PVF)]. Failure to seroconversion (PVF) is possibly due to the persistence of maternal antibodies in children vaccinated at younger age and is believed to be the principal reason to why some vaccinees remained susceptible to measles [20], although vaccine-related factors such as inappropriate handling of the vaccine and poor cold-chain regulation should not be ignored [26, 28, 30, 37]. In this regard, in our earlier study the impact of specific antibodies on the immunogenicity of MMR vaccine giving after the age of 12 months was investigated. Results showed that lower serocoversion rates and lower levels of specific antibodies were observed among infants with retained maternal antibodies beyond the age of 12 months than those without retained maternal antibodies [35]. Also, in a comparative study between two groups of children that were vaccinated with 2 doses of MMR vaccine scheduled at the ages of 15 months and 6 years VS 12 and 18 months, the immunogenicity of MMR vaccine was investigated. Results showed lower rates of seroconversion among both groups of children just before giving MMR2: 74%, 82.3%, and 68% VS 78.9%, 68% and 68% respectively. After MMR2, these rates approached to 94.4%, 94.4% and 92.4% VS 98.2%, 97%, and 87%, respectively [38]. Similar to our results were also reported in one study from Tehran [29]. In that study which was performed by Tabatebaei et al, the immunogenicity of MMR1 vaccine was investigated among 12–15 month-old Tehranian children. Their results showed that following MMR1 vaccination, 75,8%, 95,3%, and 73,8%, of vaccinated children were seroconverted, to measles, mumps, and rubella respectively [29]. Furthermore, in a similar study, the immunogenicity of MMR vaccine administered to ≥ 12 month-old children under the strict control of researchers for cold-chain regulation, the seroconversion rate was 91.2% [30]. The possible negative impact of poor cold-chain controlling on the immunogenicity of measles containing vaccine was also postulated by other researchers [28, 37]. When comparison was made between our findings and other data from the Iran with those that were reported worldwide [1, 8, 11, 24, 25], the rates of PVF detected in Iranian studies were higher. In most of these studies administering MMR1 vaccine at the age 12–13 months, was associated with 90–95% seroconversion rates for M-R component of the MMR vaccine [1, 24, 25]. The main possible reason for the higher rates of PVF observed in our study as well as other studies from Iran may be due to presence of low concentrations of specific antibodies, particularly anti- measles antibody, undetectable by ELISA method, and its negative influence on the immunogenicity of the MMR vaccine. However, the possible negative impact of technical problems in vaccination procedure should be also considered. Further studies are recommended to investigate the presence of specific antibodies, particularly measles antibody by a more sensitive method just before MMR1 immunization at the age 12-13months as well as its effects on the immunogenicity of MMR vaccine. Also, periodic educational sessions for vaccinators are suggested to improve vaccination techniqes, particularly cold-chain regulation.
Most serosusceptible children following MMR1, acceptably seroconverted with boosted antibodies after administration of MMR2 at the age of 18 months. However the overall seroprotection rates detected in this study were lower than expected in the world. Results of most studies indicated that vaccination with 2-doses of MMR vaccine after the age of 12 months is associated with > 95–98% seroconversion rate [1, 8–11], but the results of most studies from Iran vary considerably [28, 38]. While the result of one study from north of Iran showed seroconversion rates of 98,2% and 94,4% after MMR2 given at the age of 6 years or 18 months [38], respectively, in another study from Ahwaz 6 months after MMR vaccination of 6.5 year- old children with history of 2-doses of monovalent measles vaccination at the ages of 9 and15 months, the seroprevalence rate was 45.6%, for measles ,76.7%for mumps and 87.7% for rubella [28]. However, our data in this study indicated acceptable, but not optimal seroprotection rates among Iranian children following two-doses of MMR immunization.
While considering these rates of seroprotection along with 97%of vaccine coverage rates in all districts of the country a population immunity rate of 89.9%, 87.6% and 89.9% for MMR agents could be estimated, respectively. The concerning point is that vaccine- induced antibodies against measles and mumps decrease faster over time compare to rubella [17–19] (secondary vaccine failure). Therefore, an increasing number of potentially measles-mumps susceptible population will accumulate in the community and facilitate outbreaks even among fully vaccinated subjects [12–14]. However, this rates of herd immunity against measles is lower than is required to eliminate/sustain measles elimination [ 8–11]. The rates for mumps and rubella are at the lowest threshold to eliminate mumps and rubella epidemics [4, 8]. Therefore, in mid-and long-term, these levels of immunogenicity are challenging, and raise concern about the sustaining measles- rubella elimination in the country with certificate of elimination which was achieved in the last 2 years [39]. In this regard, monitoring and controlling cold-chain regulation in the primary health care centers to preserve vaccine potency, and periodic serosurveillance to monitor immunity against MMR agents are recommended. Further studies with larger sample size using more sensitive laboratory methods to measure low levels of specific antibodies just before MMR1 immunization are suggested. If these results are confirmed by further studies, changing the age of the first dose of MMR vaccine to 14 to15 months and/or considering additional universal dose of MMR vaccine at the older age are recommended.
The main limitations of this study include its small sample size and also using two brands of MMR vaccine interchangeably that may influence the final results.