Mumps serum antibody levels before and after an outbreak to assess infection and immunity in vaccinated students

Since the end of 2009, various mumps outbreaks have occurred in the Netherlands. The outbreaks affected mostly young adults, who had been twice vaccinated with the measles, mumps, and rubella (MMR) vaccine in childhood [1]. This phenomenon could be due to waning immunity in this age group, because antibody responses after vaccination last shorter than after natural infection. In the absence of mumps virus circulation, a substantial proportion of persons is seronegative 15 years after the second MMR vaccination [2, 3]. Furthermore, recent findings suggest that the MMR vaccine is not very effective in eliciting an antibody response of high avidity against mumps compared with measles and rubella [4], which also could explain the poor protection of vaccinated adolescents. Mumps attack rates above 10% among vaccinated university students have been reported during various recent outbreaks [5, 6]. Those attack rates were based on a particular setting within a specific time frame, and they are therefore probably higher than overall attack rates in a nationwide outbreak. In contrast, attack rates may be underestimated because calculations are based on self-reporting of mumps symptoms, whereas many mumps virus infections run an asymptomatic course [7–9]. In theory, more reliable attack rates could be obtained from measuring mumps-specific immunoglobulin (Ig)G concentrations, because these generally increase after mumps virus infection [10]. However, a challenge is the lack of a serological correlate of protection in vaccinated individuals. Only 1 study has shown that pre-outbreak mumps antibody neutralization titers in patients with mumps were lower than in persons who were not infected with mumps virus during the outbreak, but it was not possible to set a cutoff point separating all clinical patients with mumps from nonpatients [3]. In this study, we first measured mumps-specific IgG antibody concentrations in paired pre- and post-outbreak samples from exposed students in 2 Dutch university cities to identify mumps virus infections. In this way, we could calculate the proportions of symptomatic and asymptomatic infections and determine attack rates and risk factors for mumps virus infection, irrespective of clinical outcome. Second, to identify a correlate of protection, mumps-specific IgG concentrations in pre-outbreak samples were compared between infected and non-infected persons.