Additional Evidence on Serological Correlates of Protection against Measles: An Observational Cohort Study among Once Vaccinated Children Exposed to Measles

Abstract

To assess correlates of protection against measles and against subclinical measles virus (MV) infection, we recruited once-vaccinated children from geographic regions associated with increased MV circulation and/or at schools with low vaccination coverage in the Netherlands. Paired blood samples were collected shortly after onset of the measles outbreak and after the outbreak. A questionnaire was used to document the likelihood of exposure to MV and occurrence of measles-like symptoms. All blood samples were tested for MV-specific antibodies with five different assays. Correlates of protection were assessed by considering the lowest neutralizing antibody levels in children without MV infection, and by ROC analyses. Among 91 participants, two seronegative children (2%) developed measles, and an additional 19 (23%) experienced subclinical MV infection. The correlate of protection against measles was lower than 0.345 IU/mL. We observed a decreasing attack rate of subclinical MV infection with increasing levels of specific antibodies until 2.1 IU/mL, above which no subclinical MV infections were detected. The ROC analyses found a correlate of protection of 1.71 IU/mL (95% CI 1.01–2.11) for subclinical MV infection. Our correlates of protection were consistent with previous estimates. This information supports the analyses of serosurveys to detect immunity gaps that require targeted intervention strategies.

A Population-Based Threshold of Protection for COVID-19 Vaccines

“…The expectation is that a concentration of the relevant biomarker (most commonly a level of antibody) can be found above which individuals are reasonably likely to be protected. This method has been applied to a number of diseases such as measles 4,5 and meningococcus 6 , typically by evaluating outbreaks of disease in which, fortuitously, pre-outbreak sera were available. The method has rarely been used in largescale vaccine trials because of the inconvenience and expense of collecting sera on all participants, but some COVID-19 vaccine trials are an exception.…”

Assessment of the Clinical and Economic Impact of Different Immunization Protocols of Measles, Mumps, Rubella and Varicella in Internationally Adopted Children

“…However, severe adverse events are extremely rare, and we speculate that our results are not or are minimally affected by this omission. Lastly, there is no absolute association between being unprotected (seronegative) and not having protective antibody titers, since immune response to vaccines is complex and relies on different immunologic mechanisms which are not all explored by serology testing [27]. In fact, current data does not give conclusive evidence what level of antibodies should be considered protective for MMRV, even if it seems that high levels of circulating antibodies are important in protection against outbreaks [28][29][30].…”

Immunization Status against Measles, Mumps, Rubella and Varicella in a Large Population of Internationally Adopted Children Referred to Meyer Children’s University Hospital from 2009 to 2018

“…Indeed, it must be considered that our center was able to recruit only a part of all the adopted children arriving in Tuscany, as some parents may have consulted their primary care pediatrician or no one at all. Lastly, there is no absolute association between being unprotected and not having protective antibody titers, since immune response to vaccines is complex and relies on different immunologic mechanisms, which are not all explored by serology testing [33].…”