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Toward an Improved Meningococcal Serogroup B Assay
1Janssen Vaccines & Prevention B.V., Bacterial Vaccine Discovery and Early Development, Leiden, Netherlands jpoolman@its.jnj.com.
Abstract:
Because 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.
Insights
Predicting the effectiveness of MenB vaccines is challenging due to strain diversity. The meningococcal antigen surface expression (MEASURE) assay shows promise but requires further investigation, with enzyme-linked immunosorbent assay (ELISA) as a potential alternative.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Invasive Neisseria meningitidis serogroup B (MenB) strains exhibit diverse surface structures, complicating vaccine efficacy prediction.
- Traditional human serum bactericidal assays (hSBA) are impractical for assessing MenB vaccine effectiveness against varied strains.
- The meningococcal antigen surface expression (MEASURE) assay quantifies factor H binding protein (fHbp) expression using flow cytometry.
Purpose of the Study:
- To evaluate the utility of the MEASURE assay in predicting MenB strain susceptibility to antibody-mediated killing.
- To map a cross-reactive antibody binding epitope relevant to MenB vaccine efficacy.
- To explore alternative, potentially more reproducible assays for MenB vaccine assessment.
Main Methods:
- Utilized flow cytometry for the meningococcal antigen surface expression (MEASURE) assay.
- Quantitated factor H binding protein (fHbp) expression on invasive MenB strains.
- Investigated antibody binding epitope mapping and strain susceptibility to killing.
Main Results:
- The MEASURE assay was explored for its potential in predicting MenB strain susceptibility to antibody-mediated killing.
- McNeil et al. mapped a cross-reactive antibody binding epitope.
- Questions remain regarding MenB strains with high fHbp expression that are nonsusceptible to anti-fHbp antibody killing.
Conclusions:
- The MEASURE assay shows potential but requires further validation for predicting MenB vaccine efficacy.
- Alternative methods like a standardized enzyme-linked immunosorbent assay (ELISA) may offer greater reproducibility and accessibility.
- Understanding strain-specific factors influencing susceptibility to antibody-mediated killing is crucial for MenB vaccine development.
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