title: Diversity of factor H-binding protein in Neisseria meningitidis carriage isolates.
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.
authors.affiliation: Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, PA, United States. jwmarsh@pitt.edu
authors.forename: Jane W
authors.initials: JW
authors.lastname: Marsh
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Shutt
authors.forename: Rolando
authors.initials: R
authors.lastname: Pajon
authors.forename: Mary M
authors.initials: MM
authors.lastname: Tulenko
authors.forename: Stephen
authors.initials: S
authors.lastname: Liu
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Hollick
authors.forename: Julia A
authors.initials: JA
authors.lastname: Kiehlbauch
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Clark
authors.forename: David S
authors.initials: DS
authors.lastname: Stephens
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Arnold
authors.forename: Robert A
authors.initials: RA
authors.lastname: Myers
authors.forename: Leonard W
authors.initials: LW
authors.lastname: Mayer
authors.forename: Lee H
authors.initials: LH
authors.lastname: Harrison
mesh_terms: D000293:Adolescent; D000942:Antigens, Bacterial / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D002353:Carrier State / Q000382:microbiology*; D014644:Genetic Variation; D005845:Georgia; D006801:Humans; D008396:Maryland; D008589:Meningococcal Infections / Q000382:microbiology* / Q000517:prevention & control; D022401:Meningococcal Vaccines; D009345:Neisseria meningitidis / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D011995:Recombination, Genetic; D012703:Serotyping
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; C484699:factor H-binding protein, Neisseria meningitidis