Waning of Maternal Antibodies Against Measles, Mumps, Rubella, and Varicella in Communities With Contrasting Vaccination Coverage

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 [3]. 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 [9]. 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 [10].

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 [15]. 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 [15]. 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.