Toward an Improved Meningococcal Serogroup B Assay.

Jan Poolman

doi:10.1128/mbio.00713-18

Abstract

ABSTRACTBecause of diverse sequences and differential expression of surface structures on individual invasive Neisseria meningitidis serogroup B (MenB) strains, predicting the efficacy of MenB vaccines using traditional human serum bactericidal assays (hSBA) is impractical. The meningococcal antigen surface expression (MEASURE) assay uses flow cytometry to quantitate the expression of factor H binding proteins (fHbp) contained in the bivalent rLP2086 MenB vaccine. To date, experience with MEASURE has been lacking, and in a long-awaited article, McNeil et al. (mBio 9:e00036-18, https://doi.org/10.1128/mBio.00036-18), provide detailed mapping of a cross-reactive antibody binding epitope and explore the potential utility of MEASURE in predicting the susceptibility of individual MenB strains to antibody-mediated killing. Remaining questions center around why some strains with high fHbp expression are nonsusceptible to anti-fHbp antibody killing. Consideration of alternative methods, such as a standardized enzyme-linked immunosorbent assay (ELISA), might offer a more readily available and reproducible assay for wider use.

Highlights

The first highly protective pediatric meningococcal vaccines were licensed for use in 1999, followed rapidly by the development of multivalent meningococcal conjugate vaccines targeting up to four serogroups (A, C, W, and Y)
The correlation between bactericidal antibody titers and the level of factor H binding proteins (fHbp) detected in the meningococcal antigen surface expression (MEASURE) assay was poor
The authors were able to show that bacteria were usually susceptible to bactericidal killing when the mean fluorescence intensity (MFI) was at least 1,000, which equated with 30 pg of fHbp per microgram of total cell protein

Summary

Introduction

The first highly protective pediatric meningococcal vaccines (serogroup C protein conjugate vaccines) were licensed for use in 1999, followed rapidly by the development of multivalent meningococcal conjugate vaccines targeting up to four serogroups (A, C, W, and Y). MEASURE assay, which uses flow cytometry to quantitate the mean fluorescence intensity (MFI) indicating fHbp surface expression on individual MenB strains.

Results

Conclusion