Measurement of measles virus-specific neutralizing antibodies: evaluation of the syncytium inhibition assay in comparison with the plaque reduction neutralization test

Abstract

Plaque reduction neutralization (PRN) is the “gold-standard” for the measurement of measles-specific neutralizing antibodies. However, it is a complicated assay and tends to be operator-dependent. It has been suggested that the simpler syncytium inhibition assay (SIA) can give results comparable to the PRN test. We compared these two assays using 594 serum or plasma samples obtained from children at various times after natural infection, primary measles immunization, and measles revaccination. The results of the two assays correlated well overall (r = .86; p < 0.0001). The strain of challenge virus (wild-type versus vaccine strain) did not significantly influence SIA titers and the assay performed equally well with serum and plasma. PRN titers ≥120 and >800 are thought to indicate protection against clinical illness and infection respectively. The equivalent SIA cut-off values using 125 plaque-forming units as the challenge inoculum were ≥16 and >128 respectively. At low PRN titers (<200), the correlation between PRN and SIA values was reasonable (r = 0.60; p < 0.001) when a challenge inoculum of 12.5 plaque-forming units was used. At the lowest PRN titers (<100), 15% of the samples gave divergent results. These data confirm the utility of the SIA in the determination of measles-specific neutralizing antibodies when antibody titers are high. However, the PRN assay remains the test of choice when maximum sensitivity at low titers is required.