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Diversity of factor H-binding protein in Neisseria meningitidis carriage isolates
Authors:Marsh Jane W  Shutt Kathleen A  Pajon Rolando  Tulenko Mary M  Liu Stephen  Hollick Rosemary A  Kiehlbauch Julia A  Clark Thomas A  Stephens David S  Arnold Kathryn E  Myers Robert A  Mayer Leonard W  Harrison Lee H
Affiliation:a Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, PA, United States
b Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, CA, United States
c Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
d Laboratories Administration, Maryland Department of Health and Mental Hygiene, Baltimore, MD, United States
e Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States
f Emory University, Robert W. Woodruff Health Sciences Center, Atlanta, GA, United States
g Medical Research Service, VA Medical Center, Atlanta, GA, United States
h Georgia Division of Public Health and Emerging Infections Program, Atlanta, GA, United States
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.
Keywords:Meningococcal vaccine   FHbp   Genetic lineage   Recombination
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