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Diversity of factor H-binding protein in Neisseria meningitidis carriage isolates
Jane W Marsh1, Kathleen A Shutt, Rolando Pajon
1Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, PA, United States. jwmarsh@pitt.edu
Abstract:
Several meningococcal vaccines under development for prevention of serogroup B disease target the factor H-binding protein (FHbp), an immunogenic lipoprotein expressed on the surface of Neisseria meningitidis. Based upon sequence and phylogenetic analyses, FHbp can be classified into 3 protein variants (1, 2 or 3) or 2 subfamilies (A or B). The potential effect of FHbp-containing vaccines on meningococcal carriage is not known. We determined the diversity of FHbp among a population of carriage isolates obtained from Georgia and Maryland high school students in 1998 and 2006-2007. Analysis of the fHbp gene sequence from 408 carriage isolates identified 30 different FHbp protein sequences. The majority of carriage isolates harbored FHbp proteins belonging to variant 2/subfamily A. Association between FHbp proteins and genetic lineage was observed among the carriage isolates. However, split decomposition analysis, together with tests of linkage disequilibrium and pairwise homoplasy suggest recombination at fHbp contribute to allelic diversity. Of note, the FHbp proteins in serogroup B vaccines under development are either absent or not well represented in this carriage population. The FHbp genetic repertoire observed in carriage isolate populations will be useful in understanding the potential impact of FHbp-containing vaccines on meningococcal carriage.
Insights
Meningococcal vaccines targeting factor H-binding protein (FHbp) may not cover common strains found in carriage isolates. Most carriage isolates harbor FHbp variant 2/subfamily A, which is underrepresented in current vaccine candidates.
Area of Science:
- Microbiology
- Vaccinology
- Genetics
Background:
- Neisseria meningitidis serogroup B causes significant disease.
- Factor H-binding protein (FHbp) is a target for serogroup B vaccines.
- The impact of FHbp-based vaccines on meningococcal carriage is unknown.
Purpose of the Study:
- To determine the diversity of FHbp in meningococcal carriage isolates.
- To assess the representation of FHbp variants in carriage isolates compared to vaccine candidates.
Main Methods:
- Analysis of fHbp gene sequences from 408 carriage isolates collected in 1998 and 2006-2007.
- Phylogenetic and sequence analyses to classify FHbp variants and subfamilies.
- Recombination and linkage disequilibrium analyses to understand genetic diversity.
Main Results:
- Identified 30 distinct FHbp protein sequences among carriage isolates.
- FHbp variant 2/subfamily A was the most prevalent.
- FHbp variants targeted by current vaccines were largely absent or underrepresented in carriage isolates.
- Evidence of recombination contributing to FHbp diversity.
Conclusions:
- The FHbp diversity in carriage isolates suggests current vaccine candidates may have limited coverage.
- Understanding FHbp genetic repertoire is crucial for predicting vaccine impact on meningococcal carriage.
- Further research is needed to ensure vaccine efficacy against circulating strains.
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