Diversity of factor H-binding protein in Neisseria meningitidis carriage isolates

• Type of Material: Article
• Authors: Jane W. Marsh, University of Pittsburgh; Kathleen A. Shutt, University of Pittsburgh; Rolando Pajon, Children's Hospital Oakland Research Institute; Mary M. Tulenko, University of Pittsburgh; Stephen Liu, University of Pittsburgh; Rosemary A. Hollick, Johns Hopkins University; Julia A. Kiehlbauch, Maryland Department of Health and Mental Hygiene; Thomas A. Clark, Centers for Disease Control and Prevention; David Stephens, Emory University; Kathryn E. Arnold, Georgia Division of Public Health; Robert A. Myers, Maryland Department of Health and Mental Hygiene; Leonard W. Mayer, Centers for Disease Control and Prevention; Lee H. Harrison, University of Pittsburgh
• Language: English
• Date: 2011-08-11
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.vaccine.2011.06.025
• Title of Journal or Parent Work: Vaccine
• ISSN: 0264-410X
• Volume: 29
• Issue: 35
• Start Page: 6049
• End Page: 6058
• Grant/Funding Information: This study was supported in part by the Centers for Diseases Control and Prevention. Sanofi Pasteur supported the 2006–2007 meningococcal carriage study through a grant to the CDC Foundation.
• Keywords: HERD-IMMUNITY; Science & Technology; VACCINE; SEROGROUP-B MENINGOCOCCUS; DISEASE; IMMUNOGENICITY; MEDICINE, RESEARCH & EXPERIMENTAL; COMPONENTS; LIPOPROTEIN; STRAINS; COVERAGE; Research & Experimental Medicine; Medicine, Research & Experimental; FHbp; Genetic lineage; Immunology; EVOLUTIONARY; Meningococcal vaccine; IMMUNOLOGY; Recombination; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Immunology; Health Sciences, Pharmacology

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.