Evaluation of different measles IgG assays based on recombinant proteins using a panel of low-titre sera

During the WHO campaign to eradicate measles, accurate discrimination between immune and non-immune individuals will become increasingly important. Due to waning immunity in vaccinated populations, the performance of a measles IgG assay depends mainly on its ability to detect reliably seronegative individuals among many vaccinees with low antibody levels. New serological tests based on recombinant proteins detect only a fraction of the total measles virus (MV) specific antibodies. Therefore, several assays based on recombinant MV-haemagglutinin (ELISA and flow cytometry) or MV-fusion protein (flow cytometry) as well as neutralisatlon and haemagglutination test have been evaluated using a large panel of low-titre and negative sera. Since such an evaluation is highly dependent on threshold values for positivity, the receiver operating characteristic curve analysis was applied. The H-FACS and the H-ELISA showed the best performing characteristics (specificity: 97.4 and 96.1%, respectively; sensitivity: 88.1 and 89.6%, respectively) and may be an alternative to the neutralisation assay. The number of undefined/grey zone sera was significantly lower compared to a commercial whole virus-based ELISA and therefore fewer individuals would be vaccinated unnecessarily.