Development of a Measles and Rubella Multiplex Bead Serological Assay for Assessing Population Immunity.

Abstract

Serosurveys are important tools for estimating population immunity and providing immunization activity guidance. The measles and rubella multiplex bead assay (MBA) offers multiple advantages over standard serological assays and was validated by comparison with the enzyme-linked immunosorbent assay (ELISA) and the measles plaque reduction neutralization (PRN) assay. Results from a laboratory-produced purified measles whole virus antigen MBA (MeV WVAL) correlated better with ELISA and PRN than results from the baculovirus-expressed measles nucleoprotein (N) MBA. Therefore, a commercially produced whole virus antigen (MeV WVAC) was evaluated. Serum IgG antibody concentrations correlated significantly with a strong linear relationship between the MeV WVAC and MeV WVAL MBAs (R=0.962, R2=0.926). IgG concentrations from the MeV WVAC MBA showed strong correlation with PRN titers (R=0.846) with a linear relationship comparable to values obtained with the MeV WVAL MBA and PRN assay (R2=0.716 and R2=0.768, respectively). Receiver-operating characteristic (ROC) curve analysis of the MeV WVAC using PRN titer as the comparator resulted in a seroprotection cutoff of 153 mIU/ml, similar to the established correlate of protection of 120 mIU/ml, with a sensitivity of 98% and a specificity of 84%. IgG concentrations correlated strongly between the rubella WVA MBA and ELISA (R=0.959 and R2=0.919). ROC analysis of the rubella MBA using ELISA as the comparator yielded a cutoff of 9.36 IU/ml, similar to the accepted cutoff of 10 IU/ml for seroprotection, with a sensitivity of 99% and a specificity of 100%. These results support use of the MBA for multi-antigen serosurveys assessing measles and rubella population immunity.