Waning of Maternal Antibodies Against Measles, Mumps, Rubella, and Varicella in Communities With Contrasting Vaccination CoverageSandra Waaijenborg1,3, Susan J. M. Hahné1, Liesbeth Mollema1, Gaby P. Smits2, Guy A. M. Berbers2, Fiona R. M. van der Klis2, Hester E. de Melker1, Jacco Wallinga1
Correspondence: Sandra Waaijenborg, PhD, National Institute of Public Health and the Environment, Centre for Infectious Disease Control, Epidemiology and Surveillance Unit, PO Box 1, 3720 BA Bilthoven, the Netherlands (firstname.lastname@example.org).
Presented in part: European Society for Pediatric Infectious Diseases, The Hague, the Netherlands (poster) June 2011. Partly presented as a poster at the Nordic Vaccine meeting, Copenhagen, 5–7 September 2012.
Background. The combined measles, mumps, and rubella (MMR) vaccine has been successfully administered for >20 years. Because of this, protection by maternal antibodies in infants born to vaccinated mothers might be negatively affected.
Methods. A large cross-sectional serologic survey was conducted in the Netherlands during 2006–2007. We compared the kinetics of antibody concentrations in children and women of childbearing age in the highly vaccinated general population with those in orthodox Protestant communities that were exposed to outbreaks.
Results. The estimated duration of protection by maternal antibodies among infants in the general population, most of whom were born to vaccinated mothers, was short: 3.3 months for measles, 2.7 months for mumps, 3.9 months for rubella, and 3.4 months for varicella. The duration of protection against measles was 2 months longer for infants born in the orthodox communities, most of whom had unvaccinated mothers. For rubella, mothers in the orthodox communities had higher concentrations of antibodies as compared to the general population.
Conclusions. Children of mothers vaccinated against measles and, possibly, rubella have lower concentrations of maternal antibodies and lose protection by maternal antibodies at an earlier age than children of mothers in communities that oppose vaccination. This increases the risk of disease transmission in highly vaccinated populations.
In many industrialized countries, the introduction of measles, mumps, and rubella (MMR) vaccine into national immunization programs proved successful in reducing the incidence of these infectious diseases [1, 2]. Infants typically receive the first dose of vaccine around the first year of age . Maternally derived antibodies provide the primary protection for infants prior to this first vaccine dose. The initial concentration of maternal antibodies in a newborn is highly correlated with the antibody concentration in their mother [4–8]. Subsequently, there is waning of the maternal antibody levels in the infant, leaving the child susceptible to infections. Optimal timing of the first dose of vaccine can contribute to keeping this period as short as possible. This is important because, among European infants aged <1 year, measles risk and severity are greater than the risk and severity among those aged ≥1 year . The optimal timing of the first MMR vaccine dose depends on 2 main factors. First, the infant's immune system should be sufficiently mature to respond to the vaccine antigens. Second, levels of maternal antibodies must be low enough to ensure that they do not neutralize the live, attenuated strains in the vaccine. Insight in the kinetics and determinants of maternal antibody concentrations is therefore very important .
A known determinant of the maternal measles virus antibody concentration is the vaccination status of the mother. Mothers who received MMR vaccine tend to have a lower concentration of measles virus–specific antibodies than mothers who naturally acquired measles [11–13]. Infants born to measles-vaccinated mothers are hence likely to have lower levels maternal antibodies at birth and a shorter period of protection than infants of mothers who acquired measles naturally [14–16]. In countries with high MMR vaccination coverage, such as the Netherlands, most women of childbearing age are vaccinated against measles and have avoided natural infection. A lower duration of protection by maternal antibodies against measles might provide a motivation to lower the age at which the first dose of measles vaccine is administered to infants, but the degree and duration of immune response is uncertain when the vaccine is administered to infants aged <12 months. Since the measles vaccine is combined with mumps and rubella vaccines into the trivalent MMR vaccine, the question arises how the vaccination history of the mother affects the duration of protection against mumps and rubella. At present, it is not known how long infants are protected by maternal antibodies against infection or how long they remain susceptible to mumps and rubella before the first dose of vaccine is administered.
The Netherlands provides a unique setting in which to study the effects of maternal vaccination on the kinetics of maternal antibodies because, owing to orthodox Protestant beliefs, a considerable proportion of the population refuses vaccination . Since many of these individuals are sociogeographically clustered in the so-called Dutch Bible belt, outbreaks of measles, mumps, and rubella are still occurring here [16–18]. The last outbreaks of measles and rubella occurred in 1999–2000 and 2004–2005, respectively. We studied the duration of protection against measles, mumps, and rubella by comparing infants in the general population, in which most mothers have been vaccinated, with infants in orthodox reformed communities, in which mothers tend to refuse vaccination . We use statistical modeling to infer the kinetics of maternal antibody levels in infants and to quantify any difference in duration of immunity between infants of mothers in the general population and mothers in orthodox reformed communities. To validate our comparison between these 2 groups, we also considered varicella, against which vaccination is not included in the national immunization program.